POU2F2-mediated upregulation of lncRNA PTPRG-AS1 inhibits ferroptosis in breast cancer via miR-376c-3p/SLC7A11 axis.

Background: Triple-negative breast cancer (TNBC) is a subtype of BC with high rates of mortality. The mechanism of PTPRG-AS1 in ferroptosis of TNBC was investigated. Methods: Chromatin immunoprecipitation and dual-luciferase reporter assays were used to measure intermolecular relationships. MTT and colony formation assays detected cell viability and proliferation. Kits detected Fe2+ and reactive oxygen species levels. The role of PTPRG-AS1 in tumor growth was analyzed in vivo. Results: PTPRG-AS1 was increased in TNBC tissues and cells. PTPRG-AS1 silencing increased the reduction of glutathione and GPX4, increased Fe2+ and reactive oxygen species in erastin-treated cells and inhibited proliferation. POU2F2 transcriptionally upregulated PTPRG-AS1. PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11. PTPRG-AS1 knockdown suppressed tumor growth in vivo. Conclusion: POU2F2 transcriptionally activates PTPRG-AS1 to modulate ferroptosis and proliferation by miR-376c-3p/SLC7A11, promoting TNBC.

Triple-negative breast cancer (TNBC) is a kind of breast cancer with high recurrence and low survival rates. Activation of the ferroptosis pathway can inhibit BC proliferation and distant metastasis. Therefore, identifying effective biomarkers and molecular mechanisms of ferroptosis in TNBC is important for its earlier detection and therapy. PTPRG-AS1 is a new type of lncRNA discovered in recent years that is increased in various diseases and is related to prognosis. In the present study, the authors found that POU2F2 promoted PTPRG-AS1 transcription. PTPRG-AS1 knockdown activated ferroptosis in TNBC and inhibited proliferation. Mechanistically, PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11, thereby inhibiting ferroptosis and promoting TNBC development. These results indicate that PTPRG-AS1 is a possible therapeutic target in TNBC.

Corrigendum: Probiotics for the treatment of docetaxel-related weight gain of breast cancer patients-A single-center, randomized, double-blind, and placebo-controlled trial.

[This corrects the article DOI: 10.3389/fnut.2021.762929.].

Breast cancer combined with contralateral neck lymph node metastasis: a case report.

BACKGROUND: Contralateral neck lymph node metastasis is rare in primary breast cancer. Its clinical staging and treatment principles lack authoritative guidelines. A case of a 30-year-old breast cancer patient with contralateral neck lymph node metastasis is presented. The clinical treatment is discussed in combination with current research. CASE PRESENTATION: A 30-year-old woman presented with a right breast mass for 5 months and left neck lymph node enlargement for 5 days. Mammography showed a 33 mm*14.3 mm mass in the inner quadrant of the right breast. The ultrasound showed several hypoechoic nodules on the left side of the neck. Rapid intraoperative pathological examination diagnosed a right breast malignant tumor and poorly differentiated carcinoma of the left cervical lymph nodes. Then, right mastectomy was performed immediately. The patient was scheduled to undergo chemotherapy, molecular targeted therapy, radiotherapy and endocrine therapy after the operation. The long-term efficacy remains to be seen. CONCLUSION: The infrequent presentation of breast cancer with metastasis to the contralateral neck lymph node can be challenging for standard therapies.

Primary breast angiosarcoma: A case report.

Background: Primary breast angiosarcoma (PBA) is a rare sarcoma, accounting for only 0.04% of all breast malignancies, with a difficult diagnosis and a poor prognosis. Mastectomy is the standard treatment, and the role of adjuvant treatment (chemotherapy and/or radiotherapy following surgery) remains uncertain with very few studies. Case Presentation: We report the case of a 17-year-old female patient who presented with a right breast lump that had rapidly increased in size and was hemorrhaging. She was diagnosed with breast angiosarcoma by needle biopsy and pathological evaluation. However, the mass showed a quick tendency to bleed during biopsies. After that, we performed angiography and tumor vascular embolization. The patient underwent a mastectomy followed by adjuvant chemotherapy. Conclusion: Tumor vascular embolization reduced the surgical risk of PBA with hemorrhage complications. Postoperative therapeutic roles still need further exploration and verification.

Hormone Receptor Expression on Endocrine Therapy in Patients with Breast Cancer: A Meta-Analysis.

OBJECTIVE: To evaluate the role of hormone receptor expression on endocrine therapy in patients with breast cancer. METHODS: The databases were used to collect the effect of high expression and low expression of hormone receptors on the efficacy of endocrine therapy in breast cancer. Two evaluators independently screened the literature based on preset inclusion and exclusion criteria. The quality of the article was evaluated using a modified Newcastle-Ottawa Scale (NOS) system. The survival data included in the literature were extracted and the ln(hazard ratio (HR)) and se[ln(HR)] of the overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) rates were calculated according to different level of hormone receptors. The RevMan 5.3 software was used to evaluate the meta-analysis. RESULTS: A total of 13 relevant literature were included in the study. There were 8318 estrogen receptor (ER)-positive and 7926 progesterone receptor (PR)-positive patients. Overall survival, DFS, and RFS rates in high expression of ER(+) patients were significantly higher in low expression of ER(+) patients (OS HR = .59, 95% confidence interval (CI): .46-.76, P < .0001; DFS HR = .62, 95%CI: .50-.76, P < .00001; RFS HR = .44, 95% CI: .33-.58, P < .00001). In patients with high expression of PR(+), OS, DFS, and RFS rates were significantly higher than those with low expression of PR(+) (OS HR = .66, 95% CI: .57-.78, P < .00001; DFS HR = .52, 95% CI: .42-.65, P < .00001; RFS HR = .24, 95% CI: .11-.53, P = .0004). CONCLUSION: The expression of ER and PR are powerful predictors of adjuvant endocrine therapy response. Breast cancer patients with high expression of hormone receptors benefit more from endocrine therapy and have better prognosis.

Safety of Breast Cancer Mastoscopic Surgery from the Perspective of Immunity and Adipokines.

Background: This study was performed to explore the safety of breast cancer (BC) mastoscopic surgery from the perspective of immunity and adipokines. Method: A single-center, prospective, randomized controlled trial was carried out among 42 patients who had undergone surgery from December 2018 to July 2019. All patients were randomly divided into an open surgery group (n = 21) and a mastoscopic surgery group (n = 21). Flow cytometry was used to detect natural killer (NK), CD4+ T cells, CD8+ T cells, and regulatory T (Treg) cells in each group 1 d before surgery, 1 h after operation, and 1, 5, and 7 d after operation. The levels of serum leptin and adiponectin were detected by enzyme-linked immunosorbent assay before and after operation. Results: There were no significant differences in the percentages of NK (p = 0.984), CD4+ T (p = 0.591), Treg (p = 0.676), and CD8 + T (p = 0.341) lymphocytes between the two groups during the perioperative period. There were no significant differences in the levels of serum leptin and adiponectin before and after operation between the two groups (all p > 0.05). There were no significant differences between patients undergoing open surgery and mastoscopic surgery from the perspective of immunity and adipokines. Conclusion: Mastoscopic surgery is a suitable surgical choice for patients with BC.

Probiotics for the Treatment of Docetaxel-Related Weight Gain of Breast Cancer Patients-A Single-Center, Randomized, Double-Blind, and Placebo-Controlled Trial.

Background: Docetaxel is an important chemotherapy-agent for breast cancer treatment. One of its side-effects is weight gain, which increases the all-cause mortality rate. Considering gut microbiota is one important factor for weight regulation, we hypothesized that probiotics could be potentially used to reduce the docetaxel-related weight gain in breast cancer patients. Methods: From 10/8/2018 to 10/17/2019, 100 breast cancer (Stage I-III) patients underwent four cycles of docetaxel-based chemotherapy were enrolled and randomly assigned to receive probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) or placebo (supplementary material of the probiotics capsule) treatment for 84 days with three capsules per time, twice/day. The primary outcome: the changes in body weight and body-fat percentage of the patients were measured by a designated physician using a fat analyzer, and the secondary outcomes: the fasting insulin, plasma glucose, and lipids were directly obtained from the Hospital Information System (HIS); The metabolites were measured using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS); The fecal microbiome was analyzed using bacterial 16S ribosomal RNA (rRNA) gene sequence. All indicators were measured 1 day before the first cycle of docetaxel-based chemotherapy and 21 days after the last cycle of docetaxel-based chemotherapy. Results: Compared with the placebo group, the probiotic group showed significantly smaller changes in body weight (Mean [SD] 0.77 [2.58] vs. 2.70 [3.08], P = 0.03), body-fat percentage (Mean [SD] 0.04 [1.14] vs. 3.86 [11.09], P = 0.02), and low density lipoprotein (LDL) (Mean [SD]-0.05[0.68] vs. 0.39 [0.58], P = 0.002). Moreover, five of the 340 detected plasma metabolites showed significant differences between the two groups. The change of biliverdin dihydrochloride (B = -0.724, P = 0.02) was inverse correlated with weight gain. One strain of the phylum and three strains of the genus were detected to be significantly different between the two groups. Also, the changes of Bacteroides (B = -0.917, P < 0.001) and Anaerostipes (B = -0.894, P < 0.001) were inverse correlated with the change of LDL. Conclusions: Probiotics supplement during docetaxel-based chemotherapy for breast cancer treatment may help to reduce the increase in body weight, body-fat percentage, plasma LDL, and minimize the metabolic changes and gut dysbacteriosis. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=24294, ChiCTR-INQ-17014181.

New approaches in chimeric antigen receptor T-cell therapy for breast cancer. / 嵌合抗原受体Tç»†èƒžç–—æ³•åœ¨ä¹³è ºç™Œä¸­çš„åº”ç”¨è¿›å±•.

Chimeric antigen receptor (CAR) T-cells has gained remarkable effect in hematologic malignancy. Breast cancer (BC) is the most popular malignancy tumor in women. Although surgical treatment, radiotherapy, endocrine therapy and molecular targeted therapy increase cure ratio of BC, it is still the major cause for cancer death among women. CAR-T cells can promote anti-breast cancer activity in vivo and in vitro preclinical studies. At present, some studies attempt to push the boundary of CAR T-cell therapy in the BC area. The results indicate that CAR-T cells may be an effective method for BC.

CTGF enhances resistance to 5-FU-mediating cell apoptosis through FAK/MEK/ERK signal pathway in colorectal cancer.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers among both males and females; the chemotherapy drug 5-fluorouracil (5-FU) is one of a doctors' first lines of defense against CRC. However, therapeutic failures are common because of the emergence of drug resistance. Connective tissue growth factor (CTGF) is a secreted protein that binds to integrins, and regulates the invasiveness and metastasis of certain carcinoma cells. Here, we found that CTGF was upregulated in drug-resistant phenotype of human CRC cells. Overexpression of CTGF enhanced the resistance to 5-FU-induced cell apoptosis. Moreover, downregulating the expression of CTGF promoted the curative effect of chemotherapy and blocked the cell cycle in the G1 phase. We also found that CTGF facilitated resistance to 5-FU-induced apoptosis by increasing the expression of B-cell lymphoma-extra large (Bcl-xL) and survivin. Then we pharmacologically blocked MEK/ERK signal pathway and assessed 5-FU response by MTT assays. Our current results indicate that the expression of phosphorylated forms of MEK/ERK increased in high CTGF expression cells and MEK inhibited increases in 5-FU-mediated apoptosis of resistant CRC cells. Therefore, our data suggest that MEK/ERK signaling contributes to 5-FU resistance through upstream of CTGF, and supports CRC cell growth. Comprehending the molecular mechanism underlying 5-FU resistance may ultimately aid the fight against CRC.

Inhibiting the role of Skp2 suppresses cell proliferation and tumorigenesis of human gastric cancer cells via the upregulation of p27kip1.

Gastric cancer is a malignant disease of the digestive system with high rates of incidence and mortality. S­phase kinase­associated protein 2 (Skp2) is a novel oncogene, which has been identified to be important in tumor progression and metastasis. In order to clarify the role of Skp2 in human gastric cancer, the present study detected the expression of Skp2 in human gastric cancer tissues, and investigated the molecular mechanism of Skp2 in the progression of gastric carcinoma. The results of the initial bioinformatics analysis showed that Skp2 was significantly upregulated in 31 specimens of primary gastric cancer from a UK patient cohort, and in 10 gastric cancer lines of a side population, compared with normal gastric tissues (P<0.01). Specimens from 47 patients with gastric cancer and 19 normal gastric tissue specimens were obtained and analyzed using western blot analysis. The positive rate of expression of Skp2 was 87.2%, indicating that the expression of Skp2 was observed in 41 specimens of the detected gastric cancer samples, whereas the positive rate of the expression of Skp2 was 5.6% in the normal gastric samples (P<0.01). In the human gastric cancer cell lines, the defective regulation of Skp2 or presence of an Skp2 inhibitor inhibited the proliferation of BGC­823 and MKN­45 cells. In addition, the Skp2 inhibitor suppressed the proliferation of gastric cancer cells in a time­ and dose­dependent manner. Furthermore, transfection with Skp2 short hairpin (sh)RNA or treatment with SKP inhibitor C1 for 48 and 72 h led to the accumulation of p27kip1 in Hela cells. Tumorigenicity experiments involving nude mice showed that interference of the expression of Skp2 inhibited the growth of the human gastric tumor cells in the nude mice, and the tumor weights and volumes in the Skp2 shRNA group were significantly lower, compared with those in the negative control shRNA group (P<0.01) and untreated group (P<0.01). Taken together, these data suggested that Skp2 acted as an oncogene in human gastric cancer, and that Skp2­mediated p27kip1 degradation contributed to the progression of gastric cancer. Abrogating the effects of Skp2 may effectively inhibit the growth of gastric cancer cells, which may be useful as a novel target in the clinical treatment of gastric cancer.

Mastoscopic sentinel lymph node biopsy in breast cancer.

BACKGROUND: Previous studies have demonstrated that mastoscopic sentinel lymph node biopsy (MSLNB) has good identification rate (IR) and low false negative rate (FNR). However, few studies have directly compared the surgical performance and peri- and post-operative factors of MSLNB with conventional sentinel lymph node biopsy (SLNB). METHODOLOGY: Sixty patients diagnosed with breast cancer were recruited and randomly assigned to one of the three groups: MSLNB, SLNB and SLNB with lipolysis injection. Peri- and post-operative parameters were compared using general linear models. To examine the effect of age on these parameters, we performed separate analysis stratified by age (≤50 years old vs. >50 years old). RESULTS: Patients in the MSLNB group experienced longer surgery and suffered higher surgical cost than patients who underwent conventional SLNB or SLNB with lipolysis injection (p<0.0001). Despite this, they had significantly less blood loss than those who underwent conventional SLNB (22.0±7.0 ml vs.73.5±39.6 ml; p<0.0001). Analysis by age group indicates a similar pattern of difference among the three groups. MSLNB and conventional SLNB have similar IR and FNR. CONCLUSION: As a minimally invasive technique, MSLNB can significantly reduce blood loss while providing similar IR and FNR, indicating that it can be a promising alternative to conventional SLNB. CONCLUSION: Variations in popliteal artery terminal branching pattern occurred in 7.4% to 17.6% of patients. Pre-surgical detection of these variations with MD CTA may help to reduce the risk of iatrogenic arterial injury by enabling a better surgical treatment plan.

[Construction and identification of shRNA expressing vectors targeting RhoA gene].

AIM: To construct and identify shRNA interference vector targeting RhoA gene. METHODS: Two pairs of single stranded oligonucleotides encoding RhoA siRNA sequence were designed and synthesized. After annealing, its were inserted into vector pGPU6/GFP/Neo, constructed recombinant vectors and then were identified by restrictive digestion and DNA sequencing. LoVo cells were transfected with the recombinant DNA samples by the liposome complex method, and then fluorescence photographs were taken. RESULTS: Enzyme digestion and DNA sequencing showed that the oligonucleotide fragments were correctly inserted into pGPU6/GFP/Neo vector. CONCLUSION: The RhoA gene-targeted siRNA and its vector are successfully constructed.