Successful Outcome of a Patient with Concomitant Pancreatic and Renal Carcinoma Receiving Secoisolariciresinol Diglucoside Therapy Alone: A Case Report.

Introduction: Pancreatic cancer (PC) is among the deadliest malignancies. Kidney cancer (KC) is a common malignancy globally. Chemo- or radio-therapies are not very effective to control PC or KC, and overdoses often cause severe site reactions to the patients. As a result, novel treatment strategies with high efficacy but without toxic side effects are urgently desired. Secoisolariciresinol diglucoside (SDG) belongs to plant lignans with potential anticancer activities, but clinical evidence is not available in PC or KC treatment. Patient Concerns: We report a rare case of an 83-year-old female patient with pancreatic and kidney occupying lesions that lacked the conditions to receive surgery or chemo- or radiotherapy. Diagnosis: Pancreatic and kidney cancers. Interventions: We gave dietary SDG to the patient as the only therapeutics. Outcomes: SDG effectively halted progression of both PC and KC. All clinical manifestations, including bad insomnia, loss of appetite, stomach symptoms, and skin itching over the whole body, all disappeared. The initial massive macroscopic hematuria became microscopic and infrequent, and other laboratory results also gradually returned to normal. Most of the cancer biomarkers, initially high such as CEA, CA199, CA724, CA125, came down rapidly, among which CA199 changed most radically. This patient has had progression-free survival of one year so far. Conclusion: These results demonstrate the potent inhibitory effects of SDG on PC and KC of this patient and provide promising novel therapeutics for refractory malignant tumors.

Redox/pH-responsive hollow manganese dioxide nanoparticles for thyroid cancer treatment.

The nano drug delivery system MnO2/CDDP@PDA-Cy5.5 was synthesized in this study to increase the efficacy of Cisplatin (CDDP) on thyroid cancer and alleviate the damage to normal tissue, with the aim of enhancing the anti-cancer efficacy, increasing the drug load, optimizing the control of drug release, and alleviating the systemic toxicity arising from drug off-target. On that basis, high efficacy and low toxicity win-win can be obtained. In this study, hollow manganese dioxide nanoparticles (MnO2 NPs) were prepared based on the template method. CDDP was loaded into the hollow cavity and then modified with polydopamine (PDA) and Cy5.5, with the aim of obtaining the nano-drug loading system MnO2/CDDP@PDA-Cy5.5 NPs. The NPs precisely delivered drugs by intelligently responding to the tumor microenvironment (TME). As indicated by the release curves, the NPs release CDDP rapidly by inducing the decomposition of PDA and MnO2 under acidic or redox conditions, and Magnetic resonance imaging (MRI) contrast agent Mn2+ was generated. The results of the in vivo MRI studies suggested that T1 contrast at the tumor site was notably enhanced under the Enhanced permeability and retention (EPR) effect. After the intravenous administration, the effective tumor accumulation exhibited by the NPs was confirmed by magnetic resonance imaging as a function of time. Compared with free CDDP, the in vivo therapeutic effect was remarkably increased. As indicated by the above-described results, MnO2/CDDP@PDA-Cy5.5 NPs is a drug delivery system exhibiting diagnostic and therapeutic functions.

Magnetic resonance/fluorescence dual-modality contrast agents targeting αvß6-overexpressing tumors based on A20FMDV2 peptide as a ligand.

Pancreatic ductal adenocarcinoma (PDAC) is a malignant digestive system tumor with a poor late-stage prognosis. This study aimed to identify new methods for the early detection of PDAC. The nanoprobe A20FMDV2-Gd-5-FAM was developed using A20FMDV2 (N1AVPNLRGDLQVLAQKVART20-NH2, A20FMDV2) as the ligand and characterized using dynamic light scattering, transmission electron microscopy, Fourier transform infrared analysis, and UV absorption spectroscopy. The binding of pancreatic cancer cells AsPC-1, MIA PaCa-2, and normal human pancreatic H6C7 cells (HPDE6-C7) to the probe was verified using laser confocal microscopy, and the biocompatibility of the probe was evaluated in vivo. In vivo magnetic resonance and fluorescence imaging were also performed on nude mice with subcutaneous pancreatic tumor xenografts to verify the bimodal imaging performance of the probe. The probe exhibited good stability and biocompatibility and an enhanced relaxation rate (25.46 ± 1.32 mM-1 s-1) than Gd-DTPA. Confocal laser scanning microscopy results revealed that the A20FMDV2-Gd-5-FAM probe could be successfully ingested and internalized, and infrared analysis results demonstrated that the probe was linked successfully. Finally, magnetic resonance T1WI imaging and intravital fluorescence imaging demonstrated the specific signal enhancement of the probe at the tumor site. In conclusion, the bimodal molecular probe A20FMDV2-Gd-5-FAM showed a stable magnetic resonance and fluorescence bimodal imaging performance and is a promising new approach for diagnosing early-stage cancers with a high integrin αvß6 expression.

Aptamer-mediated hollow MnO2 for targeting the delivery of sorafenib.

Sorafenib (SRF) presents undesirable effects in clinical treatment, due to the lack of targeting, poor water solubility, and obvious side effects. In this study, we constructed a novel nanodrug carrier system for accurate and efficient delivery of SRF, improving its therapeutic effects and achieving tumor-specific imaging. The hollow mesoporous MnO2 (H-MnO2) nanoparticles equipped with target substance aptamers (APT) on the surface were used to load SRF for the first time. The resulting H-MnO2-SRF-APT could specifically bound to glypican-3 (GPC3) receptors on the surface of hepatocellular carcinoma (HCC), rapidly undergoing subsequent degradation under decreased pH conditions in the tumor microenvironment (TME) and releasing the loaded SRF. In this process, Mn2+ ions were used for T1-weighted magnetic resonance imaging simultaneously. The in vitro cell experiments indicated that H-MnO2-SRF-APT showed much more effects on the inhibition in the proliferation of Huh7 and HepG2 HCC cells than that of the non-targeted H-MnO2-SRF and free SRF. Besides, the in vivo results further confirmed that H-MnO2-SRF-APT could effectively inhibit the growth of xenograft tumors Huh7 in the naked mouse with good biosafety. In conclusion, H-MnO2-SRF-APT could significantly enhance the therapeutic effect of SRF and is expected to be a new way of diagnosis and treatment of HCC.

TDMQ20, a Specific Copper Chelator, Reduces Memory Impairments in Alzheimer's Disease Mouse Models.

Besides targeting amyloid or tau metabolisms, regulation of redox metal ions is a recognized therapeutic target for Alzheimer's disease (AD). Based on the bioinorganic chemistry of copper, we designed specific chelators of copper(II) (TDMQs) insight to regulate copper homeostasis in the brain and to inhibit the deleterious oxidative stress catalyzed by copper-amyloid complexes. An oral treatment by TDMQ20 was able to fully reverse the cognitive and behavioral impairment in three different murine models, two nontransgenic models mimicking the early stage of AD and a transgenic model representing a more advanced stage of AD. To our knowledge, such a comparative study using the same molecule has never been performed. Regular C57BL/6 mice received a single injection of human Cu-Aß1-42 in the lateral ventricles (icv-CuAß) or in the hippocampus (hippo-CuAß). In both cases, mice developed a cognitive impairment similar to that of transgenic 5XFAD mice. Oral administration of TDMQ20 to icv-CuAß or hippo-CuAß mice within a 16-day period resulted in a significant improvement of the cognitive status. The 3-month treatment of transgenic 5XFAD mice with TDMQ20 also resulted in behavioral improvements. The consistent positive pharmacological results obtained using these different AD models correlate well with previously obtained physicochemical data of TDMQ20. The short-term novel object recognition (NOR) test was found particularly relevant to evaluate the rescue of declarative memory impairment. TDMQ20 was also able to reduce the oxidative stress in the mouse cortex. Due to its reliability and facile use, the hippo-CuAß model can be considered as a robust nontransgenic model to evaluate the activity of potential drugs on the early stages of memory deficits.

Detection and Separation of Smoke From Single Image Frames.

This paper proposes novel methods for detecting and separating smoke from a single image frame. Specifically, an image formation model is derived based on the atmospheric scattering models. The separation of a frame into quasi-smoke and quasi-background components is formulated as convex optimization that solves a sparse representation problem using dual dictionaries for the smoke and background components, respectively. A novel feature is constructed as a concatenation of the respective sparse coefficients for detection. In addition, a method based on the concept of image matting is developed to separate the true smoke and background components from the smoke detection results. Extensive experiments on detection were conducted and the results showed that the proposed feature significantly outperforms existing features for smoke detection. In particular, the proposed method is able to differentiate smoke from other challenging objects (e.g. fog/haze, cloud, and so on) with similar visual appearance in a gray-scale frame. Experiments on smoke separation also demonstrated that the proposed separation method can effectively estimate/separate the true smoke and background components.