Autologous fat grafting (AFG) is a common technique used to enhance aesthetic outcomes in postmastectomy breast reconstruction patients. Adipokines are hormones secreted by adipose tissue that play a ...critical role in regulating metabolic processes and the immune system. However, dysregulated adipokine secretion and signaling can contribute to the development and progression of cancer by promoting angiogenesis, altering the immune response, and inducing the epithelial mesenchymal transition. We aimed to assess how breast cancer cells behave in conditioned media derived from fat grafting lipoaspirates and gain a better understanding of the potential interactions that may occur within the tumor microenvironment.
Patients who were undergoing AFG as a part of breast reconstruction at NY-Presbyterian/Weill Cornell Medical Center between March 2021 and July 2023 were consented and enrolled in the study. This study was approved by the Weill Cornell Medicine Institutional Review Board (#20-10022850-14). Conditioned media is created using 20% of patient lipoaspirate secretome and 80% starving media. The growth of MCF-7, a human ER/PR+ breast cancer cell line, in conditioned media is assessed using CyQUANT.
The breast cancer cells incubated in conditioned media displayed similar growth trends as those in complete media, which is enriched for cell growth (P > 0.05). MCF-7 cell behavior in conditioned media differed significantly from their proliferation patterns when serum starved in 100% starving media (P < 0.05).
Our results suggest that there may be inherent factors within the lipoaspirate that may promote MCF-7 proliferation. One potential implication is that AFG used for breast reconstruction should be delayed until local-regional disease control has been established. In addition, based on the in vitro proliferation patterns of breast cancer cells in conditioned media, the safety profile of AFG may be enhanced if the procedure is performed after attaining negative margins and the completion breast cancer treatment.
The development of nanomaterials that combine diagnostic and therapeutic functions within a single nanoplatform is extremely important for molecular medicine. Molecular imaging with simultaneous ...diagnosis and therapy will provide the multimodality needed for accurate diagnosis and targeted therapy. Here, gold‐coated iron oxide (Fe3O4@Au) nanoroses with five distinct functions are demonstrated, integrating aptamer‐based targeting, magnetic resonance imaging (MRI), optical imaging, photothermal therapy. and chemotherapy into one single probe. The inner Fe3O4 core functions as an MRI agent, while the photothermal effect is achieved through near‐infrared absorption by the gold shell, causing a rapid rise in temperature and also resulting in a facilitated release of the anticancer drug doxorubicin carried by the nanoroses. Where the doxorubicin is released, it is monitored by its fluorescence. Aptamers immobilized on the surfaces of the nanoroses enable efficient and selective drug delivery, imaging, and photothermal effect with high specificity. The five‐function‐embedded nanoroses show great advantages in multimodality.
Five functions in one probe: A gold‐coated iron oxide (Fe3O4@Au) nanorose with five distinct functions, which integrate aptamer‐based targeting, magnetic resonance imaging (MRI), optical imaging, photothermal and chemotherapy into one single probe is developed. This multifunctional nanoplatform is used for cancer cell targeting, dual molecular imaging, and dual therapy, with enhanced specific binding, improved cellular uptake, minimum nonspecific toxicity, and side effects.
Menin-mixed-lineage leukemia (MLL) inhibitors have potential for use as therapeutic agents for MLL-rearranged leukemia. They are also effective against solid cancers, such as breast cancer. The ...present study demonstrated that menin-MLL inhibitors, such as MI-463, unexpectedly induced the ferroptotic cell death of several cancer cell lines. MI-463 at a double-digit nM concentration markedly decreased the viable number of OVCAR-8 ovarian cancer cells for 3 days. Ferrostatin-1 (a ferroptosis inhibitor) almost completely abrogated the MI-463-induced decrease in viable cell numbers. Furthermore, the cancer cell-killing activity was inhibited by N-acetylcysteine a scavenger of reactive oxygen species (ROS), deferoxamine (DFO, an iron chelator), PD146176 (a specific inhibitor of arachidonate 15-lipoxygenase), idebenone (a membrane-permeable analog of CoQ.sub.10) and oleic acid a monounsaturated fatty acid and one of the end products of stearoyl-CoA desaturase 1 (SCD1), whereas Z-VAD-FMK (an apoptosis inhibitor) had a negligible effect on cell death. It was also found that MI-463 in combination with auranofin (a thioredoxin reductase inhibitor) synergistically increased cancer the death of breast, ovarian, pancreatic and lung cancer cell lines (88%, 14/16 cell lines). The synergistic induction of cell death was abrogated by ferroptosis inhibitor and DFO. Inhibitors of SCD1, similar to MI-463, also enhanced cancer cell death synergistically with auranofin, while inhibitors of SCD1 and MI-463 did not additively induce cell death. Treatment with zinc protoporphyrin-9, a specific inhibitor of heme oxygenase-1 (HO-1), markedly attenuated the cell death induced by MI-463 plus auranofin. On the whole, these results suggest that the MI-463-induced decrease in cell viability may be at least partly associated with the inhibition of SCD1 activity. In addition, the potent induction of HO-1 contributed to the synergistic effects of MI-463 plus auranofin. Therefore, menin-MLL inhibitors, such as MI-463, in combination with auranofin represent an effective therapeutic approach for several types of cancer via the induction of ferroptosis. Key words: menin-MLL inhibitor, MI-463, MI-503, MI-2-2, auranofin, ferroptosis, ovarian cancer cells, breast cancer cells, pancreatic cancer cells
Pancreatic cancer is one of the most fatal human cancers. Persistent and aberrant activation of signal transducer and activator of transcription 3 (STAT3) is the feature of many malignancies ...including the pancreatic cancer. Several studies reported that activated Stat3 maintains constitutive NF-kappaB activity. To determine mechanism of proliferation of pancreatic cancer cells, cell viability was examined using MTT assay. Expressions of total STAT3, phosphorylated STAT3, IkappaBalpha, cyclin D1 and survivin were determined by real-time PCR or Western blot analyses. NF-kappaB promoter activity was examined by luciferase assay. We found that activation of NF-kappaB and STAT3 as well as expression of STAT3-target genes cyclin D.sub.1 and survivin were induced in PANC-1 cells. These results indicate activation of STAT3 signaling pathway contributes to proliferation of pancreatic cancer cells. Therefore, targeting STAT3 may be beneficial for treating human pancreatic cancer.
Cancer metabolism is an essential aspect of tumorigenesis, as cancer cells have increased energy requirements in comparison to normal cells. Thus, an enhanced metabolism is needed in order to ...accommodate tumor cells' accelerated biological functions, including increased proliferation, vigorous migration during metastasis, and adaptation to different tissues from the primary invasion site. In this context, the assessment of tumor cell metabolic pathways generates crucial data pertaining to the mechanisms through which tumor cells survive and grow in a milieu of host defense mechanisms. Indeed, various studies have demonstrated that the metabolic signature of tumors is heterogeneous. Furthermore, these metabolic changes induce the exacerbated production of several molecules, which result in alterations that aid an inflammatory milieu. The therapeutic armentarium for oncology should thus include metabolic and inflammation regulators. Our expanding knowledge of the metabolic behavior of tumor cells, whether from solid tumors or hematologic malignancies, may provide the basis for the development of tailor-made cancer therapies.
3beta,12beta,25-Trihydroxydammar-(E/Z)-20(22)-ene-6-O-alpha-L-rhamnopyranosyl-(1right arrow2)-beta-D-glucopyranoside, 3beta,2beta,25-trihydroxydammar-(E/Z)-20(22)-ene-6-O-beta-D-glucopyranoside, and ...dammar-20(22)-ene-3,6,12,25-tetrol(3beta,6beta,12beta,20E/Z) were synthesized from the ginsenosides Re, Rh1, and PPT, respectively, via a simple three-step process involving acetylation, elimination-addition, and saponification. We obtained the detailed structures of these compounds by 1D and 2D NMR, and by HR-ESI-MS. Among them, dammar-20(22)-ene-3,6,12,25-tetrol(3beta,6beta,12beta,20Z) was identified as a new triterpenoid ginsenoside. The cytotoxic and hemolytic effects of these compounds towards cancer cells and erythrocytes were also evaluated.
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