This study aims to investigate the diagnostic and prognostic relevance of MMP-2 and MMP-9 as biomarkers for breast cancer, as well as their association with clinicopathological factors. Breast cancer is a leading contributor to cancer-related deaths among women worldwide. The discovery of biomarkers is crucial for early diagnosis, outcome prediction, and effective treatment. Matrix metalloproteinases (MMPs) play a significant role in various physiological and pathological activities, including development, tissue repair, inflammation, cancer spread, and metastasis. While the prognostic significance of MMP-2 and MMP-9 levels in breast cancer has been studied, the findings remain inconclusive. Participants were divided into three groups, with each group consisting of 62 individuals: Group I comprised healthy controls, Group II consisted of newly diagnosed breast cancer patients (stage I-III), and Group III included patients with metastatic breast cancer. Levels of MMP-2 and MMP-9 were evaluated in these groups using the ELISA method. An evident increase in MMP-2 and MMP-9 levels was noted when comparing the control group with both the breast cancer and metastatic groups. Furthermore, a notable correlation was identified between serum MMP-9 levels and the pathological diagnosis of breast cancer ( P < 0.001) as well as tumor size ( P < 0.01). MMP-2 and MMP-9 have emerged as promising biomarkers for breast cancer, with MMP-9 specifically associated with disease prognosis. Continued investigation into the anti-tumor mechanisms of MMPs may yield significant advancements in the development of targeted therapeutic strategies for the management of breast cancer.

Cancer cells undergo metabolic rewiring to support rapid proliferation and survival in challenging environments. Glutamine is a preferred resource for cancer metabolism, as it provides both carbon and nitrogen for cellular biogenesis. Recent studies suggest the potential anticancer activity of amino acid analogs. Some of these analogs disrupt cellular nucleotide synthesis, thereby inhibiting the formation of DNA and RNA in cancer cells. In the present study, we investigated the anticancer properties of Acivicin and Azaserine in the breast cancer MCF-7 cell line, comparing their effects to those on the non-tumorigenic MCF-10 epithelial cell line in vitro. Interestingly, at lower concentrations, both Acivicin and Azaserine showed potent inhibition of MCF-7 cell proliferation, as assessed by the MTT assay, without detectable toxicity to normal cells. In contrast, Sorafenib (Nexavar), a commonly used drug for solid tumors, showed harmful effects on normal cells, as indicated by increased lactate dehydrogenase (LDH) production in treated cells. Furthermore, unlike Sorafenib, treatment with Acivicin and Azaserine significantly affected apoptotic signaling in treated cells, indicating the role of both amino acid analogs in activating programmed cell death (PCD), as assessed by the Annexin-V assay, DAPI staining, and the relative expression of tumor suppressor genes PTEN and P53. ELISA analysis of MCF-7 cells revealed that both Acivicin and Azaserine treatments promoted the production of anti-inflammatory cytokines, including IL-4 and IL-10, while significantly reducing the production of tumor necrosis factor alpha (TNF-α). Mechanistically, both Acivicin and Azaserine treatment led to a significant reduction in the expression of glutamine synthetase (GS) at both the RNA and protein levels, resulting in a decrease in intracellular glutamine concentrations over time. Additionally, both treatments showed comparable effects on Raf-1 gene expression and protein phosphorylation when compared with Sorafenib, a Raf-1 inhibitor. Moreover, docking studies confirmed the strong binding affinity between Acivicin, Azaserine, and glutamine synthetase, as evidenced by their docking scores and binding interactions with the enzyme crystal. Collectively, these findings provide evidence for the anticancer activity of the two amino acid analogs Acivicin and Azaserine as antagonists of glutamine synthetase, offering novel insights into potential therapeutic strategies for breast cancer.

Background: Limb-salvage surgery for malignant bone tumors can be associated with considerable perioperative blood loss. The aim of this randomized controlled trial was to assess the safety and efficacy of the intraoperative infusion of tranexamic acid (TXA) in children and adolescents undergoing limb-salvage surgery. Methods: All participants were <18 years of age at the time of surgery and diagnosed with a malignant bone tumor of the femur that was treated with resection and reconstruction with a megaprosthesis. Exclusion criteria included anatomic locations other than the femur, reconstruction with a vascularized fibular graft, and a previous history of deep venous thrombosis, coagulopathy, or renal dysfunction. Participants were randomly allocated to either the TXA group (a preoperative loading dose infusion of 10 mg/kg of TXA followed by a continuous infusion of 5 mg/kg/hr until the end of surgery) or the placebo group (the same dosage but with TXA substituted with an infusion of normal saline solution). Intraoperative and perioperative blood loss were calculated with use of the hemoglobin balance method. Perioperative blood loss at postoperative day 1 and at discharge from the hospital were calculated. The total volumes of blood transfused intraoperatively and postoperatively were recorded. A statistical comparison between the groups was performed for blood loss and blood transfusion as well as for possible independent variables other than TXA, including age, body mass index, histopathologic diagnosis, tumor volume, preoperative hemoglobin level, type of resection, and the duration of surgery. Results: A total of 48 participants, with a mean age of 12.5 ± 3.44 years (range, 5 to 18 years) and a male-to-female ratio of 1.18, were included. All participants were Egyptians by race and ethnicity. There were no minor or major drug-related adverse events. There was no significant difference between the groups with respect to intraoperative blood loss (p = 0.0616) or transfusion requirements (p = 0.812), but there was a significant difference in perioperative blood loss at postoperative day 1 (p = 0.0144) and at discharge from the hospital (p = 0.0106) and in perioperative blood transfusion (p = 0.023). Conclusions: TXA can be safely infused intraoperatively in children and adolescents undergoing limb-salvage surgery, and it contributes significantly to the reduction of perioperative blood loss and transfusion requirements. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.