Preoperational diagnosis and management of breast ductal carcinoma in situ arising within fibroadenoma: Two case reports.

BACKGROUND: Ductal carcinoma in situ (DCIS) arising within fibroadenoma is a type of tumor that is rarely encountered in clinic, with only about 100 cases of carcinoma arising within a fibroadenoma reported in the literature. Here, we present two cases of breast DCIS arising within a fibroadenoma and discuss their clinical and imaging findings as well as treatment. CASE SUMMARY: The patients did not have cancer-related personal and family histories. Case 1 (a 49-year-old woman) was diagnosed with a bilateral breast nodule in May 2018 and was followed (preoperative imaging data including ultrasound and mammography) for 3 years; she underwent an excisional biopsy to address an enlargement in nodule size. Case 2 (a 37-year-old woman) was diagnosed with a left breast nodule in June 2021 and consequently received vacuum-assisted biopsy of the tumor which appeared as "irregularly shaped" and "unevenly textured" tissue on ultrasound. The pathological diagnosis was clear in both cases. Both patients underwent breast-conserving surgery and sentinel lymph node biopsy. The two cases received or planned to receive radiotherapy as well as endocrine therapy (tamoxifen). CONCLUSION: Breast DCIS arising within a fibroadenoma is rare, but patients treated with radiotherapy and endocrine therapy can have good prognosis.

Leptin promotes the proliferation and migration of human breast cancer through the extracellular-signal regulated kinase pathway.

Obesity has been associated with an increased risk of postmenopausal breast cancer, which may be due to the expression of leptin. The aim of this study was to determine the role of leptin in the growth of breast cancer cells in nude mice, the proliferation and migration of MCF-7 human breast cancer cells and its downstream signaling pathway. The xenograft mouse model was elicited by injecting MCF-7 human breast cancer cells into the left back axilla and the tumor size was measured every other day. Leptin injected subcutaneously around the tumor site led to an increase in the size and weight of the tumor, whereas the leptin antagonist (LA) significantly inhibited the size and weight of the tumor. Leptin promoted the proliferation and migration of MCF-7 cells and LA inhibited it. The effects of leptin on increasing the size and weight of the tumor in the nude mice and the proliferation and migration of MCF-7 human breast cancer cells were eradicated by pretreatment with LA, the extracellular-signal regulated kinase (ERK) inhibitor PD98059. In the xenograft mouse model the leptin level was increased and leptin increased the phosphorylation of ERK in the MCF-7 cells, whereas LA significantly reduced the phosphorylation of ERK. These results indicated that leptin promotes the growth of breast cancer in the nude mice and increases the proliferation and migration of MCF-7 human breast cancer cells via the ERK pathway.

Oridonin induces apoptosis in gastric cancer through Apaf-1, cytochrome c and caspase-3 signaling pathway.

AIM: To investigate the effect and mechanism of oridonin on the gastric cancer cell line HGC-27 in vitro. METHODS: The inhibitory effect of oridonin on HGC-27 cells was detected using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. After treatment with 10 µg/mL oridonin for 24 h and 48 h, the cells were stained with acridine orange/ethidium bromide. The morphologic changes were observed under an inverted fluorescence microscope. DNA fragmentation (a hallmark of apoptosis) and lactate dehydrogenase activity were examined using DNA ladder assay and lactate dehydrogenase-release assay. After treated with oridonin (0, 1.25, 2.5, 5 and 10 µg/mL), HGC-27 cells were collected for anexin V-phycoerythrin and 7-amino-actinomycin D double staining and tested by flow cytometric analysis, and oridonin- induced apoptosis in HGC-27 cells was detected. After treatment with oridonin for 24 h, the effects of oridonin on expression of Apaf-1, Bcl-2, Bax, caspase-3 and cytochrome c were also analyzed using reverse-transcript polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: Oridonin significantly inhibited the proliferation of HGC-27 cells in a dose- and time-dependent manner. The inhibition rates of HGC-27 treated with four different concentrations of oridonin for 24 h (1.25, 2.5, 5 and 10 µg/mL) were 1.78% ± 0.36%, 4.96% ± 1.59%, 10.35% ± 2.76% and 41.6% ± 4.29%, respectively, which showed a significant difference (P < 0.05). The inhibition rates of HGC-27 treated with oridonin at the four concentrations for 48 h were 14.77% ± 4.21%, 21.57% ± 3.75%, 30.31% ± 4.91% and 61.19% ± 5.81%, with a significant difference (P < 0.05). The inhibition rates of HGC-27 treated with oridonin for 72 h at the four concentrations were 25.77% ± 4.85%, 31.86% ± 3.86%, 48.30% ± 4.16% and 81.80% ± 6.72%, with a significant difference (P < 0.05). Cells treated with oridonin showed typical apoptotic features with acridine orange/ethidium bromide staining. After treatment with oridonin, the cells became round, shrank, and developed small buds around the nuclear membrane while forming apoptotic bodies. Lactate dehydrogenase (LDH) release assay showed that after treated with 1.25 µg/mL and 20 µg/mL oridonin for 24 h, LDH release of HGC-27 caused by apoptosis increased from 22.94% ± 3.8% to 52.68% ± 2.4% (P < 0.001). However, the change in the release of LDH caused by necrosis was insignificant, suggesting that the major cause of oridonin-induced HGC-27 cell death was apoptosis. Flow cytometric analysis also revealed that oridonin induced significant apoptosis compared with the controls (P < 0.05). And the apoptosis rates of HGC-27 induced by the four different concentrations of oridonin were 5.3% ± 1.02%, 12.8% ± 2.53%, 28.5% ± 4.23% and 49.6% ± 3.76%, which were in a dose-dependent manner (P < 0.05). After treatment for 24 h, DNA ladder showed that oridonin induced a significant increase in DNA fragmentation in a dose-dependent manner. RT-PCR revealed that mRNA expression levels were up-regulated compared with the controls in caspase-3 (0.917 ± 0.103 vs 0.357 ± 0.019, P < 0.05), cytochrome c (1.429 ± 0.111 vs 1.002 ± 0.014, P < 0.05), Apaf-1 (0.688 ± 0.101 vs 0.242 ± 0.037, P < 0.05) and Bax (0.856 ± 0.101 vs 0.278 ± 0.027, P < 0.05) (P < 0.05), whereas down-regulated in Bcl-2 (0.085 ± 0.012 vs 0.175 ± 0.030, P < 0.05). Western blotting analysis also confirmed this result. CONCLUSION: Apoptosis of HGC-27 induced by oridonin may be associated with differential expression of Apaf-1, caspase-3 and cytochrome c, which are highly dependent upon the mitochondrial pathway.