Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer: study protocol for a randomised controlled trial.

BACKGROUND: A single injection of local anaesthetic (LA) in the erector spinae plane block (ESPB) can reduce pain after modified radical mastectomy (MRM) surgery, but the duration of analgesia is affected by the duration of the LA. The aim of this study is to investigate the effect of continuous ESPB on acute and chronic pain and inflammatory response after MRM surgery. METHODS: In this prospective, randomised, controlled trial, we will recruit 160 patients, aged 18-80 years, scheduled for elective MRM surgery under general anaesthesia. They will be randomly assigned to two groups: a continuous ESPB group (group E) and a sham block group (group C). Both groups of patients will have a nerve block (group C pretended to puncture) and an indwelling catheter fixed prior to surgery. Electronic pumps containing LA are shielded. The primary outcome is the total consumption of analgesic agents. The secondary outcomes include the levels of inflammation-related cytokines; the occurrence of chronic pain (post-mastectomy pain syndrome, PMPS); static and dynamic pain scores at 2, 6, 12, 24 and 48 h postoperatively; and post-operative and post-puncture adverse reactions. DISCUSSION: Analgesia after MRM surgery is important and chronic pain can develop when acute pain is prolonged, but the analgesic effect of a nerve block with a single injection of LA is limited by the duration of drug action. The aim of this trial is to investigate whether continuous ESPB can reduce acute pain after MRM surgery and reduce the incidence of chronic pain (PMPS), with fewer postoperative analgesic drug-related complications and less inflammatory response. Continuous ESPB and up to 12 months of follow-up are two innovations of this trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ) ChiCTR2200061935. Registered on 11 July 2022. This trial is a prospective registry with the following registry names: Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer.

Design, synthesis, and anticancer activity of three novel palbociclib derivatives.

Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives (HP-1, HP-2, and HP-3) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1, HP-2, and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives.

Corrigendum: Sperm Protein Antigen 17 Expression Correlates With Lymph Node Metastasis and Worse Overall Survival in Patients With Breast Cancer.

[This corrects the article DOI: 10.3389/fonc.2019.00710.].

Sperm Protein Antigen 17 Expression Correlates With Lymph Node Metastasis and Worse Overall Survival in Patients With Breast Cancer.

Purpose: The expression and role of sperm protein antigen 17 (SPA17), which has been confirmed to be immunogenic, in breast cancer remain unclear. We examined the expression of SPA17 in breast cancer and assessed its effect on patient prognosis and its function in breast cancer development. Methods: SPA17 expression was evaluated by immunohistochemistry and Q-RT-PCR in 120 breast tissue samples. Correlation of SPA17 expression with the patients' clinicopathological parameters and overall survival was assessed. The function of SPA17 was also explored. Results: By reviewing Gene Expression Omnibus datasets, we found that SPA17 expression in ductal breast carcinoma in situ (log2[fold change] = 1.14, p-value = 0.004) and invasive ductal breast cancer (log2[fold change] = 1.03, p-value = 0.016) tissues was 2.20 and 2.05 times higher, respectively, than that in normal breast tissues. Our result also showed that 27% (27/100) of breast cancer samples expressed SPA17 but none of the normal breast (0/20) samples did. Lymph node metastasis (p < 0.001) and molecular subtyping (p = 0.002) were independent factors associated with SPA17 expression. Most importantly, SPA17 expression resulted in poor prognosis. In addition, cell function assay validated that SPA17 increased the migration (p < 0.001) and invasion (p = 0.007) of breast cancer cells, but not affected the proliferation of breast cancer cells. Conclusion: Our results demonstrated the vital role of SPA17 in the development and metastasis of breast cancer and that SPA17 may be a new therapeutic target in improving breast cancer prognosis.

Score genético predice agresividad del cáncer de próstata / Genetic score predicts aggressiveness of prostate cancer

Establecer un score genético utilizando los polimorfismos de nucleótido único (SNPs) del gen que codifica para Ribonucleasa L (RNASEL)y regiones cromosómicas 8q24 y 17q12-24 en combinación con el antígeno específico de la próstata (PSA) para predecir la agresividad del cáncer de próstata (CaP). Pacientes y métodos: hombres con CaP tratados con prostatectomía radical. Se analizaron variables clínicas y patológicas: edad al diagnóstico, PSA al diagnóstico, el volumen tumoral (TV) y extensión extracapsular (ECE) según el TNM (tumour, node and metastasis) (ECE ≥T3) y score de Gleason. Desarrollamos un modelo de puntaje genético usando regresión logística multivariable. Resultados: se incluyeron 86 pacientes sometidos a prostatectomía radical. Edad promedio fue de 62 ± 7,5 años. El promedio de PSA fue de 11,3 ± 10,6 ng/mL. Treinta y un pacientes (36 por ciento) tuvieron ECE. La mediana del TV fue de 3,8 cc. Un PSA ≥ 10 ng/mL se asoció con una mayor tasa de ECE (p <0,05) y TV más alto (p = 0,032). En el análisis univariable, los pacientes con > 1 SNP tienen mayor riesgo de ECE que los pacientes con ≤ 1 SNP (42 por ciento vs. 10,5 por ciento, p = 0,01), y los pacientes con ≥ 3 SNP tienen más TV que los pacientes con <3 SNP (60 por ciento vs. 32 por ciento, p = 0,015). Se crearon dos modelos de riesgo usando el número de SNP y PSA ≥ o <10 ng/mL para predecir ECE (sensibilidad 67 por ciento y especificidad 84 por ciento) y TV (sensibilidad 59 por ciento y especificidad 70 por ciento). Conclusiones: El score genético presentado en este estudio es una herramienta novedosa para predecir indicadores de agresividad del CaP, como ECE y TV.(AU)

To establish a genetic score using SNPs (from RNAsel and chromosomal regions 8q24 and 17q12-24) in combination with Prostate Specific Antigen (PSA) at diagnosis to predict aggressiveness of PCa (tumor volume (TV) and extracapsular extension (ECE)). Patients and methods: Men with PCa diagnosed by needle biopsy and treated with radical prostatectomy (RP). Clinical and pathological variables such as age at diagnosis, PSA at diagnosis, TV, extension of tumor according TNM (ECE ≥T3) and Gleason score where analyzed. We developed a genetic score model using Multivariate Logistic Regression. Results: We included 86 patients who underwent RP. Mean age 62 ± 7.5 years. Mean PSA was 11.3 ± 10.6 ng/mL. Thirty-one patients (36 percent) had ECE. Median TV was 3.8 cc. PSA ≥ 10 ng/mL was associated with increased rate of ECE (p <0.05) and higher TV (p = 0.032). In univariate analysis, patients with more than 1 SNP had a greater risk of ECE than patients with ≤ 1 SNP (42 percent vs. 10.5 percent, p = 0.01), and patients with ≥ 3 risk SNPs had more TV than patients with <3 SNPs risk (60 percent vs. 32 percent, p = 0.015). Two models of risk using the number of SNPs and PSA ≥ or <10 ng/mL to predict ECE (sensitivity 67 percent and specificity 84 percent) and TV (sensitivity 59 percent and specificity 70 percent) were created. Conclusions: Genetic score usingdescribed SNPs and preoperative PSA can predict aggressiveness of PCa, which would be useful to define a management with more information at diagnosis especially in localized cancers.(AU)

Retrospective observational study about reducing the false negative rate of the sentinel lymph node biopsy: Never underestimate the effect of subjective factors.

Reducing the false negative rate of sentinel lymph node biopsy (SLNB) for breast cancer patients has always been a focus of clinical research. We aimed to map the sentinel lymph nodes (SLNs) in detail, and analyze the factors related to SLNs located at locations that are often ignored by surgeons, to reduce the rate of false negatives from SLNB. A retrospective analysis involving 545 breast cancer patients who underwent SLNB in west China hospital between August 2010 and February 2016 was performed. Blue dye, radioisotope, or combined methods were used for tracing SLNs. Using blue dye, radioisotope, and a combination of blue dye and radioisotope successfully traced SLNs in 479, 507, and 525 patients, the detection rate was 88.2%, 93.9%, and 97.4%, respectively. Among the 1559 detected SLNs, 139 (9.6%) were located at the latissimus dorsi lateral margin, and 108 (6.9%) were located at level 2. Subcutaneous injection of radioisotope (P = .004) and intradermal injection of blue dye (P = .002) were independent factors associated with SLNs distributed at level 2 and the latissimus dorsi lateral margin, respectively. It was noteworthy that 2 of 7 patients had skipping metastasis in level 2, so subcutaneous injection of the isotope is strongly recommended for tracing SLNs distributed in level 2 because of the possibility of skipping metastasis. Though intradermal injection of blue dye was superior methods for tracing SLNs located at the latissimus dorsi lateral margin, we surprisingly found those patients with metastasis to the latissimus dorsi lateral margin nodes also could have metastasis to level 1 (expect for the latissimus dorsi lateral margin) nodes, it seemed that maybe there is no need to excise SLNs at the latissimus dorsi lateral margin in SLNB, whether such nodes should be regarded as useful for SLNB still needs to be determined by further large, multicenter clinical studies.

Clinicopathologic study of invasive micropapillary carcinoma of the breast.

Invasive micropapillary carcinoma (IMPC) is a rare subtype of breast carcinoma. It is presumed to be more aggressive than invasive ductal carcinoma (IDC), though it is uncertain whether the prognoses of IMPC and IDC differ. In this retrospective study, we compared the clinicopathologic characteristics and survival between 170 female patients with IMPC (pure or mixed with IDC) and 728 with pure IDC. The IMPC patients had higher clinical stages and histologic grades, higher incidences of lymphovascular invasion and axillary lymph node extracapsular extension, and a higher degree of lymph node involvement than IDC patients. Moreover, IMPC was associated with increases in estrogen receptor (ER) and progesterone receptor (PR) positivity and HER-2 overexpression. Although locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) were poorer in IMPC patients than IDC patients, overall survival and distant metastasis survival did not differ between the two groups. Multivariate analysis revealed that IMPC was an independent prognostic factor for LRRFS in breast cancer, and IMPC patients had poorer clinicopathologic characteristics and poorer RFS and LRRFS than IDC patients. We therefore suggest that to improve treatment decisions, patients with breast carcinoma be tested for the presence of this specific subtype.

Effects of vinorelbine on cisplatin resistance reversal in human lung cancer A549/DDP cells.

Multi-drug resistance (MDR) is an essential aspect of human lung cancer chemotherapy failure. Recent studies have shown that vinorelbine is involved in underlying processes in human tumors, reversing the MDR inseveral types of cancer cells. However, the roles and potential mechanism are not fully clear. In this study, we explored effects of vinorelbine in multi-drug resistance reversal of human lung cancer A549/DDP cells. We found that vinorelbine increased drug sensitivity to cisplatin and intracellular accumulation of rhodamine-123, while decreasing expression of P-glycoprotein (P-gp), multi-drug resistance-associated protein (MRP1) and glutathione-S-transferase Π (GST-Π) in A549/DDP cells. At the same time, we also established downregulation of p-Akt and decreased transcriptional activation of NF-κB and twist after vinorelbine treatment. The results indicated that vinorelbine might be used as a potential therapeutic strategy in human lung cancer.

Effect of silver nanomaterials on the activity of thiol-containing antioxidants.

The use of nanomaterials in consumer products is rapidly expanding. In most studies, nanomaterials are examined as isolated ingredients. However, consumer products such as foods, cosmetics, and dietary supplements are complex chemical matrixes. Therefore, interactions between nanomaterials and other components of the product must be investigated to ensure the product's performance and safety. Silver nanomaterials are increasingly being used in food packaging as antimicrobial agents. Thiol-containing compounds, such as reduced glutathione (GSH), cysteine, and dihydrolipoic acid, are used as antioxidants in many consumer products. In the current study, we have investigated the interaction between silver nanomaterials and thiol-containing antioxidants. The selected Ag nanomaterials were Ag coated with citrate, Ag coated with poly(vinylpyrrolidone), and Au nanorods coated with Ag in a core/shell structure. We observed direct quenching of the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) by all three Ag nanomaterials to varying degrees. The Ag nanomaterials also reduced the quenching of DPPH by GSH to varying degrees. In addition, we determined that the mixture of GSH and Au@Ag nanorods held at 37 °C was less effective at quenching azo radical than at ambient temperature. Furthermore, we determined that Au@Ag nanorods significantly reduced the ability of GSH and cysteine to quench hydroxyl and superoxide radicals. The work presented here demonstrates the importance of examining the chemical interactions between nanomaterials used in products and physiologically important antioxidants.

Dual enzyme-like activities of iron oxide nanoparticles and their implication for diminishing cytotoxicity.

Iron oxide nanoparticles (IONPs) are frequently used in biomedical applications, yet their toxic potential is still a major concern. While most studies of biosafety focus on cellular responses after exposure to nanomaterials, little is reported to analyze reactions on the surface of nanoparticles as a source of cytotoxicity. Here we report that different intracellular microenvironment in which IONPs are located leads to contradictive outcomes in their abilities to produce free radicals. We first verified pH-dependent peroxidase-like and catalase-like activities of IONPs and investigated how they interact with hydrogen peroxide (H(2)O(2)) within cells. Results showed that IONPs had a concentration-dependent cytotoxicity on human glioma U251 cells, and they could enhance H(2)O(2)-induced cell damage dramatically. By conducting electron spin resonance spectroscopy experiments, we showed that both Fe(3)O(4) and γ-Fe(2)O(3) nanoparticles could catalyze H(2)O(2) to produce hydroxyl radicals in acidic lysosome mimic conditions, with relative potency Fe(3)O(4) > γ-Fe(2)O(3), which was consistent with their peroxidase-like activities. However, no hydroxyl radicals were observed in neutral cytosol mimic conditions with both nanoparticles. Instead, they decomposed H(2)O(2) into H(2)O and O(2) directly in this condition through catalase-like activities. Transmission electron micrographs revealed that IONPs located in lysosomes in cells, the acidic environment of which may contribute to hydroxyl radical production. This is the first study regarding cytotoxicity based on their enzyme-like activities. Since H(2)O(2) is continuously produced in cells, our data indicate that lysosome-escaped strategy for IONP delivery would be an efficient way to diminish long-term toxic potential.

Dual role of selected antioxidants found in dietary supplements: crossover between anti- and pro-oxidant activities in the presence of copper.

Overproduction of reactive oxygen species (ROS) in vivo can result in damage associated with many aging-associated diseases. Defenses against ROS that have evolved include antioxidant enzymes, such as superoxide dismutases, peroxidases, and catalases, which can scavenge ROS. In addition, endogenous and dietary antioxidants play an important role in moderating damage associated with ROS. In this study, we use four common dietary antioxidants to demonstrate that, in the presence of copper (cupric sulfate and cupric gluconate) and physiologically relevant levels of hydrogen peroxide, these antioxidants can also act as pro-oxidants by producing hydroxyl radicals. Using electron spin resonance (ESR) spin trapping techniques, we demonstrate that the level of hydroxyl radical formation is a function of the pH of the medium and the relative amounts of antioxidant and copper. On the basis of the level of hydroxyl radical formation, the relative pro-oxidant potential of these antioxidants is cysteine > ascorbate > EGCG > GSH. It has been reported that copper sequestered by protein ligands, as happens in vivo, loses its redox activity (diminishing/abolishing the formation of free radicals). However, in the presence of hydrogen peroxide, cysteine and GSH efficiently react with cupric sulfate sequestered with bovine serum albumin to generate hydroxyl radicals. Overall, the results demonstrate that in the presence of copper, endogenous and dietary antioxidants can also exhibit pro-oxidative activity.

[The effect of the activation of cannabinoid receptor on the proliferation and apoptosis of hepatoma HepG2 cells].

AIM: To study the effect of the activation of cannabinoid receptor on the proliferation and apoptosis of hepatoma HepG2 cells. METHODS: HepG2 cells were treated with different doses of the activator of cannabinoid receptor-WIN-55, 212-2(WIN), MTT was used to detect the effects of WIN on HepG2 cells; Flow cytometry (FCM) was used to examine the effects of WIN on the apoptosis of HepG2 cells. Caspase 3 and c-myc proteins were determined by Western blot assay, and caspase 3, 8, 9 activity was measured using a colorimetric method. RESULTS: WIN could inhibit HepG2 cell proliferation and induce cell apoptosis dose-dependently. WIN increased caspase 3 protein levels and caspase 3, 8, 9 activity. CONCLUSION: WIN can induce apoptosis, the effect might be associated with up-regulating expression of caspases protein and down-regulating expression of c-myc protein.