Self-polymerized platinum (II)-Polydopamine nanomedicines for photo-chemotherapy of bladder Cancer favoring antitumor immune responses.

Systemic administration of platinum-based drugs has obvious limitations in the treatment of advanced bladder cancer (BC) owing to lower tumor accumulation and uncontrolled release of chemotherapeutics. There is an urgent need for advanced strategies to overcome the current limitations of platinum-based chemotherapy, to achieve maximal therapeutic outcomes with reduced side effects. In this study, self-polymerized platinum (II)-polydopamine nanocomplexes (PtPDs) were tailored for efficient chemo-photoimmunotherapy of BC. PtPDs with high Pt loading content (11.3%) were degradable under the combination of a reductive tumor microenvironment and near-infrared (NIR) light irradiation, thus controlling the release of Pt ions to achieve efficient chemotherapy. In addition, polydopamine promoted stronger photothermal effects to supplement platinum-based chemotherapy. Consequently, PtPDs provided effective chemo-photothermal therapy of MB49 BC in vitro and in vivo, strengthening the immunogenic cell death (ICD) effect and robust anti-tumoral immunity response. When combined with a PD-1 checkpoint blockade, PtPD-based photochemotherapy evoked systemic immune responses that completely suppressed primary and distant tumor growth without inducing systemic toxicities. Our work provides a highly versatile approach through metal-dopamine self-polymerization for the precise delivery of metal-based chemotherapeutic drugs, and may serve as a promising nanomedicine for efficient and safe platinum-based chemotherapy for BC.

Transcriptome Sequencing Explores the Mechanism of Baicalin on Bone Cancer Pain.

INTRODUCTION: Bone cancer pain is characterized by persistent pain, usually requiring drugs to relieve pain. Baicalin, a flavonoid compound extracted from Scutellaria baicalensis, which has antioxidant and analgesic effects. But, the effect of baicalin on bone cancer pain is unclear. Thus, this study aimed to explore the mechanism of baicalin on SD rats with bone cancer pain. MATERIALS AND METHODS: The MADB-106 breast cancer cells-induced bone pain model was constructed and carried out baicalin treatment. The therapeutic effect of baicalin on bone cancer pain model was observed by hematoxylin-eosin staining and immunofluorescence staining. We also performed transcriptome sequencing analysis of baicalin in the treatment of bone metastases. Also, RT-qPCR and ELISA were used to detect the expression levels of inflammation factors. RESULTS: After baicalin treatment, osteoclast activation was inhibited and the number of bone trabeculae was increased. Baicalin inhibited the protein expression level of inflammatory factors (IL-1ß, IL-6, TNF-α and PGE2) in the bone metastases group. Based on the transcriptome sequencing of the bone metastases group and the baicalin treatment group, baicalin inhibited the expression of ALPP, DUSP1, CYR61, ALPPL2, SPP1 and TLR4. RT-qPCR was also used to validate the expression levels of these cytokine genes. CONCLUSION: Baicalin had a certain inhibitory effect on the SD rat model of bone metastasis cancer. These insights can guide future research on the molecular mechanism of bone cancer pain and provide a theoretical basis for baicalin in the treatment of bone pain caused by breast cancer in the future.

Decellularized breast matrix as bioactive microenvironment for in vitro three-dimensional cancer culture.

Breast cancer (BC) is a leading cause of cancer-related death in women with unsatisfactory survival rates. Advances in the understanding of the genetic basis of BC provide the opportunity to develop gene-based medicines capable of treating metastatic diseases. Here, we first demonstrated efficient tissue engineering approaches applied to normal breast and BC extracellular matrix (ECM) starting from decellularized human biopsies to generate a three-dimensional (3D) bioactive model with the sodium lauryl ether sulfate solution. The decellularized tissues maximized the genetic component removal from tissues and minimally injured ECM structures and native compositions by histology and ECM compositions analyses. Importantly, we proved that the 3D ECM retained tissues biological properties. We demonstrated that after 30 days of recellularization with MCF-7 cell (human breast adenocarcinoma cell line), the 3D cancer ECM induced an overexpression of epithelial-mesenchymal transition (EMT) and cancer proliferation. Meanwhile, normal ECM from the breast inhibited EMT and cell growth with the inducement of apoptosis. Given the biological activity preserved in the ECM after decellularization, we believe these approaches are powerful tools for future preclinical research for BC and breast development.

High Spy1 expression predicts poor prognosis in colorectal cancer.

BACKGROUND: Spy1 (SPDYA) is a new discovered cell cycle protein capable of promoting cell proliferation dependent on cyclin-dependent kinase-2 activation. However, to the best of our knowledge, the expression of Spy1 in colorectal cancer (CRC) tissues remains virtually unknown. MATERIALS AND METHODS: In this retrospective study, we investigated the mRNA and protein expression levels of Spy1 in CRC tissues and corresponding non-cancerous tissues with the analyses of quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. In our research, the prognostic significances of Spy1 expression were further explored by univariate and multivariate survival analyses of 203 patients who were followed up. RESULTS: The results demonstrated that the levels of Spy1 mRNA were significantly higher in CRC tissues compared with corresponding non-cancerous tissues (p=0.0002). The results of immunohistochemistry demonstrated that the expressions of Spy1 were significantly associated with clinicopathological parameters, including T stage (χ2=7.126, p=0.028) and TNM stage (χ2=9.461, p=0.009). Kaplan-Meier analysis results indicated that high Spy1 expression (HR=2.573, p<0.001) and TNM stage (HR=1.494, p=0.011) were independent factors to predict poor prognosis for patients with CRC. CONCLUSION: We concluded that high Spy1 expression is significantly associated with unfavorable prognosis in CRC and could serve as a potential prognostic marker in clinical diagnosis of CRC.

Effect of sodium alginate on mouse ovary vitrification.

The survival rate of vitrified-thawed ovarian tissues after autotransplantation still needs to be improved. Therefore finding an ideal cryoprectant to reduce the damage to ovaries that caused by vitrification will pave the way for application of ovary cryopreservation on clinics. Experiments were conducted to investigate the effect of sodium alginate in cryoprotectant solution on mouse ovaries during the vitrification process. The ovaries obtained from 6-weeks old CD1 were assigned into six groups from A to F. Group A without treatment was used as the normal control. Group B cryopreserved with the basic cryoprotectant solution containing 15% each Me2SO and EG was used as the experimental control. Groups C, D, E, and F cryopreserved with the basic cryoprotectant solution supplemented with 0.05%, 0.10%, 0.15%, and 0.20% of sodium alginate, respectively, were assigned for the experimental groups. The in vitro analyses showed that the developmental capability of the oocytes isolated from vitrified-thawed ovaries significantly increased with increasing concentration of sodium alginate in the cryoprotectant solution (groups: A = 70 ±â€¯2; B = 43 ±â€¯2; C = 48 ±â€¯3; D = 53 ±â€¯3; E = 60 ±â€¯3; B < C < D < A, P < 0.05), and reached its highest level in group E with 0.15% of sodium alginate (P < 0.05). The lowest developmental capability of all groups was group F (41 ±â€¯1%)(P < 0.05) with 0.20% of sodium alginate. The similar results were obtained by the autotransplantation in vivo. These finding demonstrated that sodium alginate can significantly reduce the damage to ovaries by vitrification.

Cytoskeleton-associated protein 5 and clathrin heavy chain binding regulates spindle assembly in mouse oocytes.

Mammalian oocyte meiotic maturation is the precondition of early embryo development. Lots of microtubules (MT)-associated proteins participate in oocyte maturation process. Cytoskeleton-associated protein 5 (CKAP5) is a member of the XMAP215 family that regulates microtubule dynamics during mitosis. However, its role in meiosis has not been fully studied. Here, we investigated the function of CKAP5 in mouse oocyte meiotic maturation and early embryo development. Western blot showed that CKAP5 expression increased from GVBD, maintaining at high level at metaphase, and decreased after late 1-cell stage. Confocal microscopy showed there is no specific accumulation of CKAP5 at interphase (GV, PN or 2-cell stage). However, once cells enter into meiotic or mitotic division, CKAP5 was localized at the whole spindle apparatus. Treatment of oocytes with the tubulin-disturbing reagents nocodazole (induces MTs depolymerization) or taxol (prevents MTs depolymerization) did not affect CKAP5 expression but led to a rearrangement of CKAP5. Further, knock-down of CKAP5 resulted in a failure of first polar body extrusion, serious defects in spindle assembly, and failure of chromosome alignment. Loss of CKAP5 also decreased early embryo development potential. Furthermore, co-immunoprecipitation showed that CKAP5 bound to clathrin heavy chain 1 (CLTC). Taken together, our results demonstrate that CKAP5 is important in oocyte maturation and early embryo development, and CKAP5 might work together with CLTC in mouse oocyte maturation.

Increased circulating myeloid-derived suppressor cells correlate with cancer stages, interleukin-8 and -6 in prostate cancer.

AIM: Myeloid-derived suppressor cells (MDSCs) are a population of cells which negatively regulate immune response during tumor progression. In this study, we assessed the accumulation of MDSCs (CD33(+)CD11b(+)HLA-DR(-)CD14(-)) in patients with prostate cancer and its clinical relevance. METHODS: We tested the frequency of MDSCs in the peripheral blood of patients with prostate cancer or benign prostate hyperplasia and healthy donors. Serumal interleukin-8, -6 and -10 were analyzed. Effects of MDSCs on the T cell response were determined. RESULTS: MDSCs increased in cancer patients, and there was an association between MDSCs and cancer stages or overall survival. Elevated serumal interleukin-8 and -6 in cancer patients correlated with MDSCs. Moreover, accumulation of MDSCs was associated with defective T cell function. CONCLUSION: Our study showed an increased population of MDSCs in patients with prostate cancer. Interleukin-8 and -6 in serum may play a new important role companied with MDSCs in prostate cancer.

The role of Toll-like receptor (TLR) 2 and 9 in renal ischemia and reperfusion injury.

OBJECTIVE: To determine the involvement of Toll-like receptor (TLR) 2, TLR9, and TLR2+9 in renal ischemia/reperfusion (I/R) injury. METHODS: Mice with gene knock-out of TLR2, TLR9, and TLR2+9 underwent renal I/R injury. Tubular damage, expression of proinflammatory cytokines and chemokines, and kidney dysfunction were evaluated on different days after reperfusion. RESULTS: Mice deficient in TLR2, but not TLR9, were protected from renal I/R injury with less tubular damage, decreased cytokine production, and lower serum creatinine and urea levels than wild-type mice. TLR2+9 double-deficiency did not have an additional effect on tissue injury compared with TLR2 deficiency alone. CONCLUSION: These results suggest that activation of TLR2 signaling contributes to the pathogenesis of renal I/R injury, whereas TLR9 may be redundant for the development of this injury.