Regulating tumor innervation by nanodrugs potentiates cancer immunochemotherapy and relieve chemotherapy-induced neuropathic pain.

Sympathetic nerves play a pivotal role in promoting tumor growth through crosstalk with tumor and stromal cells. Chemotherapy exacerbates the infiltration of sympathetic nerves into tumors, thereby providing a rationale for inhibiting sympathetic innervation to enhance chemotherapy. Here, we discovered that doxorubicin increases the density and activity of sympathetic nerves in breast cancer mainly by upregulating the expression of nerve growth factors (NGFs) in cancer cells. To address this, we developed a combination therapy by co-encapsulating small interfering RNA (siRNA) and doxorubicin within breast cancer-targeted poly (lactic-co-glycolic acid) (PLGA) nanoparticles, aiming to suppress NGF expression post-chemotherapy. Incorporating NGF blockade into the nanoplatform for chemotherapy effectively mitigated the chemotherapy-induced proliferation of sympathetic nerves. This not only bolstered the tumoricidal activity of chemotherapy, but also amplified its stimulatory impact on the antitumor immune response by increasing the infiltration of immunostimulatory cells into tumors while concurrently reducing the frequency of immunosuppressive cells. Consequently, the combined nanodrug approach, when coupled with anti-PD-L1 treatment, exhibited a remarkable suppression of primary and deeply metastatic tumors with minimal systematic toxicity. Importantly, the nanoplatform relieved chemotherapy-induced peripheral neuropathic pain (CIPNP) by diminishing the expression of pain mediator NGFs. In summary, this research underscores the significant potential of NGF knockdown in enhancing immunochemotherapy outcomes and presents a nanoplatform for the highly efficient and low-toxicity treatment of breast cancer.

Preliminary discussion on the value of (18)F-FDG PET/CT in the diagnosis and early staging of non-mycosis fungoides/Sézary's syndrome cutaneous malignant lymphomas.

OBJECTIVE: To discuss the value of (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-PET/CT) scans in the diagnosis and early staging of non-mycosis fungoides/Sézary's syndrome cutaneous malignant lymphomas (non-MF/SS CML). MATERIALS AND METHODS: A total of 18 cases with non-MF/SS CML, confirmed by pathology or on clinical grounds, were analyzed in this study. The sensitivity of CT and PET/CT scans in the diagnosis of primary skin lesions, as well as the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CT and PET/CT scans in the diagnosis of lymph nodes (LNs) and other organs (except skin and LNs) were calculated. RESULTS: The diagnostic sensitivity of CT and PET/CT scans in the diagnosis of primary skin lesions was 82.4% (14/17) and 100% (17/17), respectively. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CT and PET/CT scans in the diagnosis of LN lesions were 55.6% (5/9), 88.9% (8/9), 72.2% (13/18), 83.3% (5/6), 66.7% (8/12), and 88.9% (8/9), 100% (9/9), 94.4% (17/18), 100% (8/8), 90.0% (9/10), respectively. The diagnostic value of the CT and PET/CT scans in the diagnosis of involvement of other organs, were 40.4% (2/5), 100% (13/13), 83.3 (15/18), 100% (2/2), 81.3% (13/16) and 80.6% (4/5), 100% (13/13), 94.4% (17/18), 100% (3/3), 92.9% (13/14), respectively. CONCLUSIONS: (18)F-FDG PET/CT has high value in the diagnosis and early staging of non-MF/SS CMLs.

Fabrication and characterization of PbO2 electrode modified with [Fe(CN)6](3-) and its application on electrochemical degradation of alkali lignin.

PbO2 electrode modified by [Fe(CN)6](3-) (marked as FeCN-PbO2) was prepared by electro-deposition method and used for the electrochemical degradation of alkali lignin (AL). The surface morphology and the structure of the electrodes were characterized by scanning electronic microscopy (SEM) and X-ray diffraction (XRD), respectively. The stability and electrochemical activity of FeCN-PbO2 electrode were characterized by accelerated life test, linear sweep voltammetry, electrochemical impedance spectrum (EIS) and AL degradation. The results showed that [Fe(CN)6](3-) increased the average grain size of PbO2 and formed a compact surface coating. The service lifetime of FeCN-PbO2 electrode was 287.25 h, which was longer than that of the unmodified PbO2 electrode (100.5h). The FeCN-PbO2 electrode showed higher active surface area and higher oxygen evolution potential than that of the unmodified PbO2 electrode. In electrochemical degradation tests, the apparent kinetics coefficient of FeCN-PbO2 electrode was 0.00609 min(-1), which was higher than that of unmodified PbO2 electrode (0.00419 min(-1)). The effects of experimental parameters, such as applied current density, initial AL concentration, initial pH value and solution temperature, on electrochemical degradation of AL by FeCN-PbO2 electrode were evaluated.