18F-fluorodeoxyglucose positron emission tomography-computed tomography in the localization of the lesions in the osteogenic region of breast cancer bone metastases after therapy.

Background: Accurate efficacy evaluation of bone metastases (BMs) from breast cancer (BC) is an intractable issue in clinical practice, for which solutions are urgently needed. This study aimed to investigate the utility of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in the response evaluation of bone metastasis of BC. Methods: In total, 22 patients diagnosed with BC and BM were enrolled. These patients underwent repeated 18F-FDG PET/CT evaluations. The patients and each BM site were divided into two groups based on their response to treatment: progressive disease (PD) and nonprogressive disease (non-PD). We analyzed and compared the changes in PET and CT images, as well as the serum concentration of carcinoembryonic antigen (CEA), carbohydrate antigen 153 (CA153), alkaline phosphatase (ALP), and calcium (Ca) over the same time frame. The immunohistochemistry (IHC) of primary lesions between groups and between the primary focus and BM with high 18F-FDG uptake were compared and analyzed. Results: Maximum standard uptake value (SUVmax) after therapy [area under the curve (AUC): 0.932] and Δ-value of SUVmax (AUC: 0.811) on 18F-FDG PET imaging proved significantly valuable for the efficacy of therapy outcomes related to BM lesions (P<0.05). In terms of overall evaluation of BM, age and human epidermal growth factor receptor 2 (HER2) expression were significantly lower in the PD group than in the non-PD group (P<0.05). There were marked differences in CEA after therapy, the changes of CEA, and CA153 (∆-value) between the groups (P<0.05). The SUVmax and Ca concentration after therapy and ∆-value of SUVmax, along with the levels of CA153, CEA, and ALP, were valuable indicators for evaluating the efficacy of individual BMs (P<0.05). IHC of BM in the PD group showed differences compared to primary lesions, with antigen Ki-67 being downregulated in metastatic lesions and HER2 being downregulated in a portion of BMs (2 of 6). Meanwhile, the expression of estrogen receptor (ER) and progesterone receptor (PR) remained relatively unchanged. Conclusions: 18F-FDG PET/CT confers precise assessment of the posttreatment efficacy pertaining to BM in BC. This modality facilitates the identification of poor effect lesions following extant therapies and localization for pathological assessment and may substantially contribute to evaluating therapeutic efficacy, refining treatment strategies, and predicting the disease trajectory of patients with BC and BM.

Next-generation sequencing-based detection in a breast MMPMN patient with EGFR T790M mutation: a rare case report and literature review.

Multiple primary malignant neoplasms (MPMNs) are difficult to identify from the metastasis or recurrence of malignant tumors. Additionally, the genetic mutations in each primary tumor vary from each other; therefore, it is critical to explore potential abnormal genes. Next-generation sequencing (NGS) technology has emerged as a reliable approach for detecting mutated genes in primary tumors and can provide several targeted therapeutic options for patients with MPMNs. Here, we report a case of metachronous multiple primary malignant neoplasm (MMPMN) patient with primary ovarian and breast cancer. Targeted NGS genetic profiling revealed a rare EGFR T790M mutation in this patient's primary breast tumor tissue, which has only been reported previously in breast cancer (BC). Based on the NGS results, osimertinib was recommended for this patient. Although this patient did not receive osimertinib because of gastrointestinal hemorrhage, this case highlights the significance of NGS technology in the diagnosis and treatment of MPMNs.

Associations between genetically predicted sex and growth hormones and facial aging in the UK Biobank: a two-sample Mendelian randomization study.

Background: Aging is an inescapable process, but it can be slowed down, particularly facial aging. Sex and growth hormones have been shown to play an important role in the process of facial aging. We investigated this association further, using a two-sample Mendelian randomization study. Methods: We analyzed genome-wide association study (GWAS) data from the UK Biobank database comprising facial aging data from 432,999 samples, using two-sample Mendelian randomization. In addition, single-nucleotide polymorphism (SNP) data on sex hormone-binding globulin (SHBG) and sex steroid hormones were obtained from a GWAS in the UK Biobank [SHBG, N = 189,473; total testosterone (TT), N = 230,454; bioavailable testosterone (BT), N = 188,507; and estradiol (E2), N = 2,607)]. The inverse-variance weighted (IVW) method was the major algorithm used in this study, and random-effects models were used in cases of heterogeneity. To avoid errors caused by a single algorithm, we selected MR-Egger, weighted median, and weighted mode as supplementary algorithms. Horizontal pleiotropy was detected based on the intercept in the MR-Egger regression. The leave-one-out method was used for sensitivity analysis. Results: SHBG plays a promoting role, whereas sex steroid hormones (TT, BT, and E2) play an inhibitory role in facial aging. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels had no significant effect on facial aging, which is inconsistent with previous findings in vitro. Conclusion: Regulating the levels of SHBG, BT, TT, and E2 may be an important means to delay facial aging.

Pseudoprogression after advanced first-line endocrine therapy in metastatic breast cancer with bone metastasis: A case report.

Approximately 75% of patients with advanced breast cancer develop bone metastasis, which significantly affects both the quality of life and the survival rate of patients. Accurate determination of the status of bone metastases is important for developing treatment strategies and the prognosis of the disease. Here, we report the case of a 33-year-old patient with advanced metastatic breast cancer (MBC) and multiple bone metastases, in which advanced first-line endocrine therapy and second-line chemotherapy were both considered unsuccessful according to the efficacy evaluation by conventional imaging. Considering the possibility of bone pseudoprogression, the original endocrine scheme was reapplied, and bone metastases achieved a great response of non-complete response (CR)/non-progressive disease (PD). This case showed that, in the course of therapy for the disease, if bone scintigraphy (BS) shows increased lesion density or new lesions, this probably indicates a favorable response (osteoblastic repair of osteolytic lesions) to therapy, and not the worsening of metastatic lesions, called bone pseudoprogression. This paper will provide new insights into strategies for the treatment of bone metastasis and shows the significance of distinguishing osteoblastic bone repair from real bone lesion progression in clinical settings.

Salvia chinensis Benth Inhibits Triple-Negative Breast Cancer Progression by Inducing the DNA Damage Pathway.

Objective: Triple-negative breast cancer (TNBC) is distinguished by early recurrence and metastases, a high proclivity for treatment resistance, and a lack of targeted medicines, highlighting the importance of developing innovative therapeutic techniques. Salvia chinensis Benth (SCH) has been widely studied for its anticancer properties in a variety of cancers. However, its significance in TNBC treatment is rarely discussed. Our study investigated the anticancer effect of SCH on TNBC and the underlying mechanisms. Methods: First, we used clonogenic, cell viability, flow cytometry, and Transwell assays to assess the effect of SCH on TNBC. Bioinformatic studies, especially network pharmacology-based analysis and RNA sequencing analysis, were performed to investigate the constituents of SCH and its molecular mechanisms in the suppression of TNBC. High-performance liquid chromatography and thin-layer chromatography were used to identify two major components, quercetin and ß-sitosterol. Then, we discovered the synergistic cytotoxicity of quercetin and ß-sitosterol and assessed their synergistic prevention of cell migration and invasion. Breast cancer xenografts were also created using MDA-MB-231 cells to test the synergistic therapeutic impact of quercetin and ß-sitosterol on TNBC in vivo. The impact on the DNA damage and repair pathways was investigated using the comet assay and Western blot analysis. Results: Our findings showed that SCH decreased TNBC cell growth, migration, and invasion while also inducing cell death. We identified quercetin and ß-sitosterol as the core active components of SCH based on a network pharmacology study. According to RNA sequencing research, the p53 signaling pathway is also regarded as a critical biological mechanism of SCH treatment. The comet assay consistently showed that SCH significantly increased DNA damage in TNBC cells. Our in vivo and in vitro data revealed that the combination of quercetin and ß-sitosterol induced synergistic cytotoxicity and DNA damage in TNBC cells. In particular, SCH particularly blocked the inter-strand cross-link repair mechanism and the double-strand breach repair caused by the homologous recombination pathway, in addition to inducing DNA damage. Treatment with quercetin and ß-sitosterol produced similar outcomes. Conclusion: The current study provides novel insight into the previously unknown therapeutic potential of SCH as a DNA-damaging agent in TNBC.

Enterococcus faecium R0026 Combined with Bacillus subtilis R0179 Prevent Obesity-Associated Hyperlipidemia and Modulate Gut Microbiota in C57BL/6 Mice.

Bacillus subtilis and Enterococcus faecium are commonly used probiotics. This study aimed to identify the effect of live combined Bacillus subtilis R0179 and Enterococcus faecium R0026 (LCBE) on obesityassociated hyperlipidemia and gut microbiota in C57BL/6 mice. Forty male C57BL/6 mice were divided into four groups: normal group (N group), model group (M group), low-dose group (L group), and high-dose group (H group). Mice were gavaged with LCBE at 0.023 g/mice/day (L group) or 0.23 g/mice/day (H group) and fed with a high-fat diet for 8 weeks. In vitro E. faecium R0026 showed an ability to lower the low-concentration of cholesterol by 46%, and the ability to lower the highconcentration of cholesterol by 58%. LCBE significantly reduced the body weight gain, Lee index, brown fat index and body mass index of mice on a high-fat diet. Moreover, LCBE markedly improved serum lipids (including serum triglyceride, total cholesterol, low-density lipoprotein and highdensity lipoprotein) while also significantly reducing liver total cholesterol. Serum lipopolysaccharide and total bile acid in L and H groups decreased significantly compared with M group. PCR-DGGE analysis showed that the composition of gut microbiota in the treatment groups was improved. Akkermansia muciniphila was found in H group. The PCA result indicated a similar gut microbiota structure between LCBE treatment groups and normal group while the number of bands and Shannon diversity index increased significantly in the LCBE treatment groups. Finally, qPCR showed Bifidobacterium spp. increased significantly in H group compared with M group, LCBE alleviated liver steatosis and improved brown adipose tissue index.

Fucoidan Protects Against High-Fat Diet-Induced Obesity and Modulates Gut Microbiota in Institute of Cancer Research Mice.

Fucoidan possesses various biological activities, such as anticoagulant, immunomodulatory, anti-inflammatory, potential antioxidant, and others. In this study, we investigated the effect of fucoidan on high-fat diet-induced obesity, inflammation, and gut microbiota in Institute of Cancer Research mice. Mice were gavaged with 50 mg/(kg·d) (Fuc0.5 group) or 250 mg/(kg·d) (Fuc2.5 group) of fucoidan for 5 weeks. Fucoidan alleviated obesity and tissue damage by decreasing body weight and body mass index, decreasing body weight gain, improved organ index, liver steatosis, and improved the structure of the small intestine. In addition, fucoidan decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol. Moreover, fucoidan reduced serum lipopolysaccharide concentrations, tumor necrosis factor-α, and total bile acid. Furthermore, fucoidan improved the structure of gut microbiota and significantly increased the abundance (Shannon diversity index, evenness, and Faecalibacterium prausnitzii) determined by denaturing gradient gel electrophoresis and quantitative PCR. In conclusion, our study provides a scientific basis for fucoidan as a functional food for modulating the gut microbiota and protecting against obesity.