Breast cancer accounts for nearly a quarter of all cancers in women worldwide, and more than 90% of women diagnosed with breast cancer undergo mastectomy or breast-conserving surgery. Retrospective clinical studies have suggested that use of regional anesthesia leads to improved patient outcomes. Laboratory studies have reported that breast cancer cells are inhibited by some local anesthetics at millimolar concentration. Here, we present a comprehensive analysis of the effects of six common local anesthetics on two human breast cancer cell lines. We used concentrations ranging from those corresponding to plasma levels during regional block by local anesthetic (plasma concentration) to those corresponding to direct infiltration of local anesthetic. Human breast cancer cell lines, MDA-MB-231 and MCF7, were incubated with each of six local anesthetics (lidocaine, mepivacaine, ropivacaine, bupivacaine, levobupivacaine, and chloroprocaine) (10 μM ~ 10 mM) for 6 to 72 h. Assays for cell viability, cytotoxicity, migration, and cell cycle were performed. High concentrations (> 1 mM) of local anesthetics applied to either MDA-MB-231 or MCF7 cells for 48 h significantly inhibited cell viability and induced cytotoxicity. At plasma concentrations (~ 10 μM) for 72 h, none of the local anesthetics affected cell viability or migration in either cell line. However, at 10 × plasma concentrations, 72-h exposure to bupivacaine, levobupivacaine or chloroprocaine inhibited the viability of MDA-MB-231 cells by > 40% (p < 0.001). Levobupivacaine also inhibited the viability of MCF7 cells by 50% (p < 0.001). None of the local anesthetics affected the viability of a non-cancerous breast cell line, MCF10A. MDA-MB-231 cell migration was inhibited by 10 × plasma concentrations of levobupivacaine, ropivacaine or chloroprocaine and MCF7 cell migration was inhibited by mepivacaine and levobupivacaine (p < 0.05). Cell cycle analysis showed that the local anesthetics arrest MDA-MB-231 cells in the S phase at both 1 × and 10 × plasma concentrations. Local anesthetics at high concentrations significantly inhibited breast cancer cell survival. At 10 × plasma concentrations, the effect of local anesthetics on cancer cell viability and migration depended on the exposure time, specific local anesthetic, specific measurement endpoint and specific cell line.

In the presence of a primary tumor, the pre-metastatic niche is established in secondary organs as a favorable microenvironment for subsequent tumor metastases. This process is orchestrated by bone marrow-derived cells, primary tumor-derived factors, and extracellular matrix. In this review, we summarize the role of pro-inflammatory cytokines including interleukin (IL)-6, IL-1β, CC-chemokine ligand 2 (CCL2), granulocyte-colony stimulating factor (G-CSF), granulocyte–macrophage colony-stimulating factor (GM-CSF), stromal cell-derived factor (SDF)-1, macrophage migration inhibitory factor (MIF), and Chemokine (C–X–C motif) ligand 1 (CXCL1) in the formation of the pre-metastatic niche according to the most recent studies. Pro-inflammatory cytokines released from tumor cells or stromal cells act in both autocrine and paracrine manners to induce phenotype changes in tumor cells, recruit bone marrow-derived cells, and form an inflammatory milieu, all of which prime a secondary organ’s microenvironment for metastatic cell colonization. Considering the active involvement of pro-inflammatory cytokines in niche formation, clinical strategies targeting them offer ways to inhibit the establishment of the pre-metastatic niche and therefore attenuate metastatic progression. We review clinical trials targeting different inflammatory cytokines in patients with metastatic cancers. Due to the pleiotropy and redundancy of pro-inflammatory cytokines, combined therapies should be designed in the future.

Metastasis or recurrence following curative surgery is the main indicator of tumor progress and is the main cause of patient death. For more than three decades, the potential for general anesthesia to affect cancer outcomes has been a subject of concern with considerable research interest. Here, we conducted this systematic review and meta-analysis to summarize the effect of inhalational anesthesia (IHNA) vs. propofol-based total intravenous anesthesia (TIVA) on metastasis and recurrence after cancer surgery from clinical and pre-clinical studies. The relative risk for metastasis/recurrence in TIVA is 0.61 (95% confidence interval (95% CI) 0.46 to 0.82, p = 0.0009) compared to IHNA. Inflammatory cytokines have been implicated in cancer metastasis following cancer surgery, thus we analyzed inflammatory cytokines levels after surgery under IHNA or TIVA. Based on pooled analysis, a lower IL-6 level was noticed in TIVA in comparison to IHNA (standardized mean difference (SMD) = 0.77, 95% CI = 0.097 to 1.44, I² = 92%, p = 0.02) but not TNF-α or IL-10. Preclinical animal model studies show that inhalational anesthetics increase the risk of breast cancer metastasis compared to propofol. In conclusion, the current evidence suggests intravenous anesthetic propofol is associated with less metastasis/recurrence and lower postoperative IL-6 level over inhaled anesthetics in the oncological surgery. We urge more well-designed clinical and preclinical studies in this field.

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that impair immune cell functions and promote tumor progression. Mounting evidence indicates that cytokines and chemokines in the tumor microenvironment alter MDSCs. Various cytokines and chemokines are involved in MDSC production, their infiltration into tumors, and their exertion of suppressive functions. Here, we consider those cytokines, chemokines, and MDSCs as an intricately connected, complex system and we focus on how tumors manipulate the MDSCs through various cytokines and chemokines. We also discuss treatment capitalizing on cytokines/chemokine signaling aimed at combating the potent immunosuppressive activities of MDSCs to improve disease outcomes.

This study aims to evaluate plasma S100A9 levels in tuberculosis (TB) patients with admission to the ICU as a marker to predict the risk of death for pulmonary severe TB. This study enrolled 256 severe TB patients admitted to Beijing Chest Hospital from Jan to Dec 2019. The S100A9 levels were measured by ELISA. Standard clinical parameters were collected. The non-parametric Mann-Whitney test, t-test, and chi-square test were applied to statistical comparison. A multivariable analysis was performed to identify risk factors for death. The plasma S100A9 levels were higher in non-survivors (25.88, 16.77–44.64) compared to survivors (15.51, 13.67–19.94). S100A9 performed better than Acute Physiology and Chronic Health Evaluation (APACHE II) score in predicting death, with AUC of 0.725, sensitivity of 65.5%, and specificity of 80.3%. By combining APACHE II score together with the S100A9 levels we got an AUC of 0.754 (95% CI 0.68 to 0.82) in predicting death. Lastly, S100A9 levels were significantly higher in patients with APACHE II score >17.5, sputum smear-positive, early death, and high cavitary lesions numbers, all of which were related to TB progression. Measurement and monitoring levels of plasma S100A9 in severe TB patients could facilitate the evaluation of patients with high risk at the early stage, which may help to improve the treatment outcome for TB patients.

Background and Objectives: Local and systemic inflammation is common after surgery and is associated with morbidity and mortality. Inflammatory cytokines have been implicated in cancer metastasis following cancer surgery. The present study aimed to analyze inflammatory cytokines levels after surgery under combined epidural/general anesthesia (EA + GA) vs. general anesthesia (GA). Methods: We systematically searched PubMed, Central, EMBASE, CINAHL, Google Scholar, and Web of Science citation indexes for clinical studies (cancer and non-cancer surgery) comparing the two techniques. We carried out a meta-analysis to evaluate the postoperative plasma levels of cytokines, C-reactive protein (CRP), and cortisol levels. Results: The literature search was last updated on 2 January 2025. We identified a total of 21 studies which compared postoperative inflammatory mediators with EA plus GA compared to GA alone. EA plus GA was associated with significantly lower serum levels of IL-6, TNF-α, CRP, as well as cortisol and other pro-inflammatory cytokines. In cancer surgery, EA plus GA was also associated with lower postoperative cytokines. Conclusions: Our meta-analysis indicates that EA plus GA is associated with diminished postoperative inflammatory response. This offers an alternative explanation for the benefit of epidural analgesia on postoperative outcomes. Considering the link between postoperative inflammation and recurrence after cancer surgery, this is an area that warrants further research.