Osteoarthritis (OA), one of the most common chronic musculoskeletal disorders, is deemed to be correlated with aging. The SIRT1 activator, resveratrol, acts as a crucial regulator of aging and may have a potential therapeutic effect on OA. Rabbit OA models were established through destabilized medial meniscus surgery. A total of 40 healthy male New Zealand rabbits were divided into five groups: control group (sham operation), OA group, as well as low dose (LD), middle dose (MD), and high dose (HD) resveratrol-treated OA groups. 6 weeks after operation, 0.8 ml of normal saline was injected into the knee joints every other day in the control and OA groups, and 0.8 ml of 5, 10, and 15 μmol/L resveratrol was injected into the knee joints every other day in the LD, MD, and HD group, respectively. The rabbits were sacrificed 2 weeks after medication, and the articular cartilage of the knee joint was collected for Micro-CT, histology and Western blot analysis. Obvious articular cartilage lesion and joint space narrowing were detected in the OA group. Compared with the OA group, less osteoarthritic changes were observed in the MD and HD groups. The MD and HD groups had significantly lower bone volume fraction, trabecular number and Mankin scores than the LD and OA groups (p < 0.05). No significant difference was found between the OA and LD groups (p > 0.05). The expressions of SIRT1 and p53 detected by western blot were consistent with the aforementioned findings. Therefore, resveratrol can activate the SIRT1 gene to play a protective role in the OA process by inhibiting chondrocyte apoptosis, trabecular bone number increasing of the subchondral bone, as well as elevation of bone density. It demonstrated the importance of SIRT1 in maintaining articular cartilage health and provided a promising therapeutic intervention in the treatment of OA.

Background: Small-sized primary tumor does not always indicate a better prognosis. We hypothesized that very small primary breast tumors with extensive lymph node (LN) metastases represented an aggressive biologic behavior in stage IV disease. Materials and Methods: Data between 2010 and 2015 were retrieved retrospectively from the Surveillance, Epidemiology, and End Results database with inclusion criteria of female sex, unilateral, metastatic, and T1/2 invasive ductal carcinoma. Primary study variables included T stage, N stage, grade, metastatic sites, number of involved sites, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status. Kaplan-Meier and adjusted Cox proportional hazards models with interaction terms were used. One-, 2- and 3-year breast cancer-specific mortality (BCSM) was examined according to tumor size. Results: We identified 5,340 eligible patients with breast cancer. In multivariate analysis, race, age, grade, molecular subtype, surgery, brain metastases, and liver metastases were found to be independently associated with BCSM. For T1 tumors, the N0, N1, and N2+ groups had the same BCSM. In tumors smaller than 50 mm, the 1-, 2-, and 3-year BCSM did not decline with the decrease of tumor size. For triple-negative breast cancers (TNBCs), the T1a/T1bN2+ group had significantly worse BCSM than any other group did. Conclusion: Patients with stage IV cancer with small-sized tumors may have BCSM as high as those with larger tumors. In TNBCs, very small tumors with severe LN involvement are associated with the worst BCSM. Continued efforts are needed to further investigate Ta1/T1bN2 + M1 TNBCs and individualize the treatment for affected patients. Implications for Practice: This study revealed that for stage IV breast cancer, smaller primary tumors were not always associated with better breast cancer-specific mortality. This study illustrated that very small triple-negative breast cancers (TNBCs) with extensive regional lymph node involvement may be a surrogate for biologically aggressive disease. Because of poor prognosis of T1a/T1bN2+ TNBCs, there might be an urgent need of more individualized treatment for affected patients. Future correlative studies ought to focus on the genetic and molecular differences in Ta1/T1bN2+ TNBCs that contribute to the biological behavior. Clarification of the regulation mechanism of very small-sized primary TNBCs with metastatic outgrowth in nodes and distant sites will play an integral role in developing targeted therapies.

Ongoing discussions persist concerning the precedence of neoadjuvant therapy (NAT) relative to adjuvant therapy (AT) for patients with T1c, node-negative, triple-negative breast cancer (TNBC), and pertinent guidelines for these individuals are absent. Women diagnosed with T1cN0M0-stage TNBC who received chemotherapy and surgery were selected from the Surveillance, Epidemiology and End Results database (2010-2020). To balance baseline characteristics and mitigate selection bias, propensity score matching (PSM) was used to create the NAT and AT cohorts. Kaplan-Meier (KM) analysis and Cox proportional hazards models were performed to assess the prognostic factors for overall survival (OS) and breast cancer-specific survival (BCSS). Logistic regression models were utilized to identify predictive factors for response to NAT. A total of 1033 patient pairs passed the PSM process, resulting in a well-balanced distribution. The KM analysis demonstrated that patients who received AT and those who underwent NAT had similar OS and BCSS, no matter before or after PSM. The multivariate Cox model showed that not achieving pathological complete response (non-pCR) following NAT, compared to AT, was associated with considerably worse OS (hazard ratio [HR], 2.207; 95 % confident intervaI [CI], 1.431-3.405; p < 0.001) and worse BCSS (HR, 2.184; 95 % CI, 1.348-3.537; p = 0.002). The logistic regression model revealed that being under 50 years old and having grade III or undifferentiated disease were independent predictors of pCR. In patients with T1cN0M0-stage TNBC, both NAT and AT resulted in equivalent OS and BCSS. However, NAT precisely helped select patients with worse prognosis.

Purpose: Ductal carcinoma in situ with microinvasion (DCISM) can be challenging to balance the risks of overtreatment versus undertreatment. We aim to identify prognostic factors in patients with DCISM and construct a nomogram to predict breast cancer-specific survival (BCSS). Materials and Methods: A retrospective cohort study of women diagnosed with DCISM from 1988 to 2015 who were identified in the Surveillance, Epidemiology and End Results database. Clinical variables and tumor characteristics were evaluated, and Cox proportional-hazards regression was performed. A nomogram was constructed from the multivariate logistic regression to combine all the prognostic factors to predict the prognosis of DCISM patients at 5 years, 10 years, and 15 years. Results: We identified 5438 total eligible breast cancer patients with a median and max survival time of 78 and 227 months, respectively. Here, patients with poorer survival outcomes were those diagnosed between 1988 and 2001, African-American race, under 40 years of age, higher tumor N stage, progesterone receptor-negative tumor, and received no surgery. The nomogram was constructed by the seven variables and passed the calibration and validation steps. The area under the receiver operating characteristic (ROC) curve (AUC) of both the training set and the validating set (5-year AUC: 0.77 and 0.88, 10-year AUC: 0.75 and 0.73, 15-year AUC: 0.72 and 0.65). Receiving chemotherapy was associated with a better BCSS (hazard ratio, HR=0.45, 95% confidence interval, 95% CI = 0.23– 0.89), especially in patients with estrogen receptor (ER) negative, progesterone receptor (PR) negative (HR = 0.35, 95% CI = 0.13– 0.97) and ER+PR-/ER-PR+ DCISM (HR = 0.07, 95% CI = 0.01– 0.59). Conclusion: Our current study is the first to construct nomograms of patients with DCISM which could help physicians identify breast cancer patients that more likely to benefit from more intensive treatment and follow-up. Chemotherapy might benefit patients with ER-PR- and ER+PR-/ER-PR+ DCISM.

The tumor microenvironment is characterized by hypoxia, resulting mainly from aberrant vascularization and insufficient blood perfusion. Under such hypoxic conditions, tumor-associated macrophages (TAMs) preferentially polarize toward an immunosuppressive M2-like phenotype, which promotes immune evasion and accelerates tumor progression. Reprogramming these M2-like TAMs into an anti-tumor M1 phenotype represents a promising therapeutic strategy, yet it remains a substantial challenge. In this study, we developed nanoparticles functionalized with mannose and an MMP-2-responsive PLGVRGD peptide. These nanoparticles undergo self-assembly in the presence of matrix metalloproteinase-2 (MMP-2), which is highly expressed in hypoxic tumor regions. The high-density mannose residues on the nanoparticle surface facilitate efficient binding to M2-like TAMs and promote their repolarization to the M1 phenotype. Moreover, the resulting system exhibits enhanced tumor tissue penetration and effectively reverses the immunosuppressive tumor microenvironment, supporting its potential as a targeted nanotherapeutic strategy for breast cancer.

Background: Invasive papillary breast cancer (IPC) is a rare cancer known to have a better prognosis than other breast cancers. This study aimed to explore whether patients with early-stage IPC can benefit from chemotherapy. Materials and Methods: IPC cases diagnosed between 2003 and 2021 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan–Meier method and the Cox proportional hazard model were performed to identify significant prognostic factors. To eliminate selection bias and baseline characteristics, propensity score matching (PSM) was used. The primary endpoints were overall survival (OS) and breast cancer-specific survival (BCSS). Results: A total of 1892 patients were enrolled, and 273 pairs were screened after PSM. Multivariable analysis showed that age under 50, married status, smaller tumor size, negative lymph node (LN) status, and receipt of surgery, chemotherapy or radiotherapy were independently associated with better OS. After PSM, patients receiving chemotherapy had significantly improved OS (P = .012), while BCSS showed no significant difference (P = .099). After stratified by tumor size and LN status, chemotherapy could significantly improve the OS of patients with LN-negative IPC with tumors ≥ 2.0 cm (P < .001). Among the patients with grade III or undifferentiated diseases, the OS of the chemotherapy group was significantly better than that of the non-chemotherapy group (P < .001). Conclusions: For patients with LN-negative IPC with tumor ≥ 2.0 cm and patients with grade III or undifferentiated disease, chemotherapy significantly improved OS. Future randomized controlled trials are expected to validate the results.