Maintenance chemotherapy is effective in patients with metastatic triple negative breast cancer after first-line platinum-based chemotherapy.

BACKGROUND: Platinum-based chemotherapy (PBCT) has gained an important position as a first-line treatment for metastatic triple-negative breast cancer (mTNBC). We assessed whether maintenance chemotherapy maintenance was superior to observation after first-line PBCT in patients with mTNBC. METHODS: A total of 265 patients with mTNBC who had exhibited non-PD after 4-6 cycles of firstline PBCT at the Fudan University Shanghai Cancer Center from January 2008 to April 2019 were retrospectively analyzed. 107 patients who did not receive additional treatment were defined as the control observation group, and the remaining 158 patients who continued to receive maintenance therapy were defined as the maintenance treatment group. RESULTS: The median progression-free survival (PFS) time in the maintenance group was 9.63 months, which was significantly longer than the PFS time of 7.47 months in the observation group (HR 0.49, 95% CI: 0.37-0.67, P<0.0001). The median overall survival (OS) of the observation group and the maintenance group was 25.37 months and 31.27 months, respectively (HR 0.65, 95% CI: 0.44-0.95, P=0.019). The survival benefit was still present after adjusting baseline characteristics. Moreover, multivariate analyses suggested that maintenance chemotherapy is an independent predictive factor for both PFS and OS. Interaction and stratified analyses showed no difference in the PFS with between the single-drug maintenance strategy, single agent or doublet group and the doublet-drug maintenance group. The most common adverse event in this study was hematologic toxicity. Except for hand-foot syndrome (0 vs. 7.6%, P=0.004), the incidence of other adverse events was not significantly different between the observation and maintenance groups. CONCLUSIONS: After achieving non-PD with the first-line PBCT in mTNBC patients, chemotherapy maintenance may provide OS benefit prior to the era of biologicals.

Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer.

Mel-18, a polycomb group protein, has been reported to act as a tumor suppressor and be down-regulated in several human cancers including gastric cancer. It was also found that Mel-18 negatively regulates self-renewal of hematopoietic stem cells and breast cancer stem cells (CSCs). This study aimed to clarify its role in gastric CSCs and explore the mechanisms. We found that low-expression of Mel-18 was correlated with poor prognosis and negatively correlated with overexpression of stem cell markers Oct4, Sox2, and Gli1 in 101 gastric cancer tissues. Mel-18 was down-regulated in cultured spheroid cells, which possess CSCs, and overexpression of Mel-18 inhibits cells sphere-forming ability and tumor growth in vivo. Besides, Mel-18 was lower-expressed in ovary metastatic lesions compared with that in primary lesions of gastric cancer, and Mel-18 overexpression inhibited the migration ability of gastric cancer cells. Interestingly, overexpression of Mel-18 resulted in down-regulation of miR-21 in gastric cancer cells and the expression of Mel-18 was negatively correlated with the expression of miR-21 in gastric cancer tissues. Furthermore, miR-21 overexpression partially restored sphere-forming ability, migration potential and chemo-resistance in Mel-18 overexpressing gastric cancer cells. These results suggests Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer cells.

Polysaccharides from Umbilicaria esculenta cultivated in Huangshan Mountain and immunomodulatory activity.

Umbilicaria esculenta cultivated in Huangshan Mountain (HSSE) is precious edible and medicinal lichen. In this study, four polysaccharide fractions designated as UEP1, UEP2, UEP3, and UEP4 were isolated from HSSE with water extraction at different temperature. The physico-chemical properties and immunomodulatory activities of polysaccharide fractions were investigated. The results indicated that UEP1, UEP2, UEP3 and UEP4 were acid polysaccharide with 0.50%, 0.62%, 0.63%, and 0.83% of uronic acid contents, respectively. Four polysaccharide fractions were mainly composed of glucose, galactose and mannose with different molar ratio. In the in vitro immunomodulatory assay, all the polysaccharide fractions (20-500 µg/mL) could increase the NO production and phagocytic activity of RAW 264.7 cells in a dose-dependent manner. This work demonstrated that the polysaccharides from HSSE could be used as potential biological response modifier.

Structural analysis and antioxidant activities of polysaccharide isolated from Jinqian mushroom.

Jinqian mushroom is a precious edible mushroom with delicious taste and high nutritional value. In this paper, a polysaccharide fraction JQPs was isolated and purified from the fruiting body of Jinqian mushroom. The chemical structure, chain conformation and antioxidant activities of JQPs were investigated. The results indicated that JQPs was mainly composed of glucose with trace amounts of xylose. The backbone of JQPs consisted of ß-(1 → 3)-D-glucan with ß-(1 → 6)-glucosyl side chain. The chain conformation analysis showed that JQPs was a triple helical polysaccharide. The antioxidant activity tests in vitro revealed that JQPs exhibited high DPPH radical and ABTS radical scavenging activities, moderate superoxide radical and hydroxyl radical scavenging activities, low reducing power and Fe(2+) chelating activities. The results suggested that JQPs could be used as a potential natural antioxidant.

Clinicopathologic significance of HER-2/neu protein expression and gene amplification in gastric carcinoma.

AIM: To study the HER-2/neu protein expression and gene amplification in gastric carcinoma and their relation. METHODS: One hundred and forty-five formalin-fixed and paraffin- embedded tumor tissue samples from Chinese gastric carcinoma patients were studied with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. Clinicopathologic data about all patients were collected. RESULTS: The levels of HER-2 3+, HER-2 2+ and HER2 1+ were measurable in 6.9%, 8.3% and 17.2% of the samples, respectively. No HER-2 was stained in 67.6% of the samples. FISH showed that HER-2 gene was amplified in 18 samples, 10 HER-2 3+ samples, 5 HER-2 2+ samples, and 3 HER-2 1+ samples with IHC staining. HER-2 status was not correlated with the sex and age of patients, and tumor size, location or differentiation, but with the depth of invasion, TNM stage, lymph node and distant metastasis as well as histopathological classification of gastric cancer (P < 0.05). CONCLUSION: All samples with IHC as HER-2 expression should be analyzed with FISH. Detection of HER-2 gene amplification can assess the malignant biological behaviors and prognosis of gastric cancer.