Activity and safety of SHR3680, a novel antiandrogen, in patients with metastatic castration-resistant prostate cancer: a phase I/II trial.

BACKGROUND: Antagonizing the androgen-receptor (AR) pathway is an effective treatment strategy for patients with metastatic castration-resistant prostate cancer (CRPC). Here, we report the results of a first-in-human phase 1/2 study which assessed the safety, pharmacokinetics, and activity of SHR3680 (a novel AR antagonist) in patients with metastatic CRPC. METHODS: This phase 1/2 study enrolled patients with progressive metastatic CRPC who had not been previously treated with novel AR-targeted agents. In the phase 1 dose-escalation portion, patients received oral SHR3680 at a starting daily dose of 40 mg, which was subsequently escalated to 80 mg, 160 mg, 240 mg, 360 mg, and 480 mg per day. In phase 2 dose-expansion portion, patients were randomized to receive daily dose of 80 mg, 160 mg, or 240 mg of SHR3680. The primary endpoint in phase 1 was safety and tolerability and in phase 2 was the proportion of patients with a prostate-specific antigen (PSA) response (≥ 50% decrease of PSA level) at week 12. RESULTS: A total of 197 eligible patients were enrolled and received SHR3680 treatment, including 18 patients in phase 1 and 179 patients in phase 2. No dose-limiting toxicities were reported and the maximum tolerated dose was not reached. Treatment-related adverse events (TRAEs) occurred in 116 (58.9%) patients, with the most common one being proteinuria (13.7%). TRAEs of grade ≥ 3 occurred in only 23 (11.7%) patients, and no treatment-related deaths occurred. Antitumor activities were evident at all doses, including PSA response at week 12 in 134 (68.0%; 95% CI, 61.0-74.5) patients, stabilized bone disease at week 12 in 174 (88.3%; 95% CI, 87.2-95.5) patients, and responses in soft tissue lesions in 21 (34.4%, 95% CI, 22.7-47.7) of 61 patients. CONCLUSION: SHR3680 was well tolerated and safe, with promising anti-tumor activity across all doses tested in patients with metastatic CRPC. The dose of 240 mg daily was recommended for further phase 3 study. TRIAL REGISTRATION: Clinical trials.gov NCT02691975; registered February 25, 2016.

Impact of different color fiber sleeves on beam hazards of 532-nm laser and vaporization efficiency.

The 532-nm laser has become increasingly popular for the treatment of urologic diseases. However, laser beam will pose significant hazards for the health of surgeons. In order to reduce beam hazards during surgery, we compared the beam hazards of laser fiber with black sleeves to the traditional fiber with transparent sleeves, and the vaporization efficiency. A total of 18 porcine kidney specimens were vaporized in normal saline at a room temperature under 532-nm laser delivered through a 760-µm core diameter side firing fiber. Two groups were divided according to the color of fiber sleeves: the transparent and the black. Each group was then divided into another three subgroups by laser power: the 80 W group, the 120 W group, and the 160 W group. The beam hazard was evaluated by light intensity measured in a sector area at a distance of 0 m, 0.5 m, and 1 m from the irradiation center. The vaporization efficiency was measured by the vaporization groove depth under the working power of 80 W, 120 W, and 160 W with a working distance of 5 mm and irradiation time of 10 s. The light intensity measured in the black fiber sleeve group is significantly lower than that in the transparent one (P < 0.01), regardless of the measuring distance (0 m, 0.5 m, and 1.0 m) and laser power (80 W, 120 W, and 160 W). No statistical difference was found on the vaporization efficiency between the groups protected by fiber sleeves of different colors (transparent/black, p > 0.05). Compared to the traditional transparent fiber sleeves, more beam hazards will be reduced in the operative region with the protection of black fiber sleeves, especially those from the irradiation center. The vaporization efficiency is not affected by the color of fiber sleeves. Such findings may offer a completely new idea for the protection of surgeons in surgeries with 532-nm lasers.

Triptorelin relieves lower urinary tract symptoms in Chinese advanced prostate cancer patients: a multicenter, non-interventional, prospective study.

BACKGROUND: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS. METHODS: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48. RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.

A comparative study of Gaussian and non-Gaussian diffusion models for differential diagnosis of prostate cancer with in-bore transrectal MR-guided biopsy as a pathological reference.

Background Although several studies have been reported on evaluating the performance of Gaussian and different non-Gaussian diffusion models on prostate cancer, few studies have been reported on the comparison of different models on differential diagnosis for prostate cancer. Purpose To compare the utility of various metrics derived from monoexponential model (MEM), biexponential model (BEM), stretched-exponential model (SEM) based diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) in the differential diagnosis of prostate cancer. Material and Methods Thirty-three patients underwent magnetic resonance imaging (MRI) examination. Multi-b value and multi-direction DWIs were performed. In-bore MR-guided biopsy was performed. Apparent diffusion coefficient (ADC), pure molecular diffusion (ADCslow), pseudo-diffusion coefficient (ADCfast), perfusion fraction (f), water molecular diffusion heterogeneity index (α), distributed diffusion coefficient (DDC), non-Gaussian diffusion coefficient (MD), and mean kurtosis (MK) values were calculated and compared between cancerous and non-cancerous groups. Receiver operating characteristic (ROC) analysis was performed for all parameters and models. Results ADC, ADCslow, DDC, and MD values were significantly lower while MK value was significantly higher in prostate cancer than those of prostatitis and benign prostatic hyperplasia. ADC, ADCslow, DDC, MD, and MK could discriminate between tumor and non-tumorous lesions (area under the curve, 0.856, 0.835, 0.866, 0.918, and 0.937, respectively). MK was superior to ADC in the discrimination of prostate cancer. DKI was superior to MEM in the discrimination of prostate cancer. Conclusions Parameters derived from both Gaussian and non-Gaussian models could characterize prostate cancer. DKI may be advantageous than DWI for detection of prostate cancer.

Results of a randomized, double-blind, active-controlled clinical trial with propiverine extended release 30 mg in patients with overactive bladder.

OBJECTIVE: To compare the efficacy and safety of the 30 mg extended release (ER) formulation of propiverine hydrochloride with the 4 mg ER formulation of tolterodine tartrate in patients with overactive bladder (OAB) in a non-inferiority trial. PATIENTS AND METHODS: Eligible patients, aged 18-75 years and with symptoms of OAB, were enrolled in this multicentre, randomized, double-blind, parallel-group, active-controlled study. After a 2-week screening period, patients were randomized at a 1:1 ratio to receive either propiverine ER 30 mg or tolterodine ER 4 mg daily during the 8-week treatment period. Efficacy was assessed using a 3-day voiding diary and patient's self-reported assessment of treatment effect. Safety assessment included recording of adverse events, laboratory test results, measurement of post-void residual urine and electrocardiograms. RESULTS: A total of 324 patients (244 female and 80 male) were included in the study. Both active treatments improved the variables included in the voiding diary and in the patient's self-reported assessment. The change from baseline in the number of voidings per 24 h was significantly greater in the propiverine ER 30 mg group compared with the tolterodine ER 4 mg group after 8 weeks of treatment (full analysis set [FAS] -4.6 ± 4.1 vs -3.8 ± 5.1; P = 0.005). Significant improvements were also observed for the change of urgency incontinence episodes after 2 weeks (P = 0.026) and 8 weeks (P = 0.028) of treatment when comparing propiverine ER 30 mg with tolterodine ER 4 mg. Both treatments were well tolerated, with a similar frequency of adverse drug reactions in both the propiverine ER 30 mg and tolterodine ER 4 mg groups (FAS 40.7 vs 39.5%; P = 0.8). More patients treated with tolterodine ER 4 mg discontinued the treatment because of adverse drug reactions compared with propiverine ER 30 mg (7.4 vs 3.1%). CONCLUSIONS: Propiverine ER 30 mg was confirmed to be an effective and well-tolerated treatment option for patients with OAB symptoms. This first head-to-head study showed non-inferiority of propiverine ER 30 mg compared with tolterodine ER 4 mg.

Low-level Ki-67 expression as an independent predictor of bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy.

OBJECTIVE: To evaluate the association of molecular markers and conventional clinicopathological factors with bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy. METHODS: The expressions of Ki-67 and P53 were measured by immunohistochemical staining prospectively in 115 consecutive patients with primary upper tract urothelial carcinoma from March 2004 to February 2014. The Cox proportional hazards regression model was used to identify independent predictors. The association between Ki-67 expression and clinicopathological variables was assessed by the χ(2) test. RESULTS: Intravesical recurrence occurred in 13 out of 115 (11.3%) patients with a mean follow-up of 54.2 months (range: 7-130). Low-level Ki-67 expression (P = 0.010), older age (>65, P = 0.040) and lower ureter tumour (P = 0.001) were independent predictors of bladder tumour recurrence in Cox regression analysis. Ki-67 expression was elevated with the progression of tumour grade (P = 0.004) but not with stage (P = 0.186). Ki-67 overexpression was also significantly higher in aggressive pathological types (P = 0.008), but only shows an inclination towards poor oncologic outcomes in the cancer-specific survival rate (P = 0.107) and the overall survival rate (P = 0.063). CONCLUSIONS: Low-level Ki-67 expression was an independent predictor for bladder tumour recurrence, while Ki-67 overexpression was associated with adverse clinicopathological parameters and poor prognosis in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy.

Prophylactic intravesical chemotherapy decreases bladder tumor recurrence after nephroureterectomy for primary upper tract urothelial carcinoma: A systematic review and meta-analysis.

PURPOSE: A high incidence of bladder tumor (BT) occurs after radical nephroureterectomy (NU) for primary upper tract urothelial carcinoma (UTUC). Although some studies have shown that prophylactic intravesical chemotherapy could prevent BT recurrence, it has not become standard practice at this stage. The purpose of this study was to evaluate the effect of intravesical instillation chemotherapy in preventing BT recurrence in patients with primary UTUC after nephroureterectomy. METHODS: A comprehensive literature search was performed in July 2014 using the Medline, Embase, and Cochrane Library databases, as well as the China National Knowledge Infrastructure and Wanfang Data. All clinical trials compared the effect of prophylactic intravesical chemotherapy after radical NU for primary UTUC. Analysis was performed using the Stata 12.0 SE software. RESULTS: Eight trials were analyzed with a total of 979 patients including 521 patients receiving intravesical chemotherapy instillation and 458 without instillation. The BT incidence rate was 125 out of 521 patients (24.0%) with intravesical instillation chemotherapy after NU, and 169 out of 458 patients (36.9%) without intravesical chemotherapy after NU. Compared with those who didn't receive instillation, the pooled odds ratio (OR) of BT recurrence was 0.45 (95% confidence interval/CI 0.34-0.61, p<0.0001) in instillation patients. In the sub-analyses, the OR of single instillation was similar to repeated instillations (0.48 and 0.42). The OR of beginning the first instillation within 24 hrs, 48 hrs and 2 weeks was 0.34, 0.48 and 0.46, respectively. CONCLUSIONS: This systematic review demonstrates that prophylactic intravesical instillation chemotherapy can prevent BT recurrence in primary UTUC patients after NU. It also suggests that single instillation may have a similar effect to repeated instillations. The first instillation beginning within 24 hrs seems to show lower BT recurrence than at 48 hrs or 2 weeks. However, given that some limitations exist, well-designed randomized controlled trials are needed to further evaluate these results.

[Use of abiraterone acetate in the treatment of patients with metastatic castration resistant prostate cancer and no prior chemotherapy: 3 case reports and literature review].

OBJECTIVE: To evaluate the safety and efficiency of using abiraterone and prednisone in the treatment of patient with metastatic castration resistant prostate cancer (mCRPC) no prior chemotherapy. METHODS: Three mCRPC no prior chemotherapy patients accepted abiraterone and prednisone treatment. The clinical data were analyzed retrospectively and the safety and efficiency of this treatment option were discussed. The Gleason scores of the three mCRPC patients were 5, 9, and 9. The clinical stages were T3aNxM0, T3aNxM1b, and T3aNxM1b. The patients received abiraterone 1 000 mg daily and prednisone 5 mg twice daily and androgen deprivation therapy in the treatment. Their blood pressure, complete blood count, prostate specific antigen (PSA), biochemical parameters, whole body CT scan and bone scan were done regularly to monitor the progression of the diseases. RESULTS: In this study, the general condition improved in two patients. Two of the three patients experienced decrease of PSA and no progression. One patient experienced disease progression. Generally, abiraterone and prednisone resulted in prolonged radiographic progression-free survival and delayed in PSA progression in mCRPC no prior chemotherapy. There were no severe side effects, such as hypokalemia, hypertension, and water-sodium retention. The patient's tolerance was good. CONCLUSION: Abiraterone and prednisone are safe and can improve mCRPC no prior chemotherapy patient's life quality and may prolong the overall survival.

[Correlation of androgen receptor CAG repeats with the risks of benign prostatic hyperplasia and prostate cancer: a meta-analysis].

OBJECTIVE: To explore the association of the androgenic receptor (AR) CAG repeats with the risks of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). METHODS: We searched the major databases at home and abroad for the literature addressing the correlation of the AR gene CAG repeats with BPH and PCa. Based on the results of heterogeneity tests, we used the M-H fixed effect model and random effect model to pool the odds ratio (OR) effect size. We evaluated publication bias by Begg and Egger bias analysis, investigated the association of CAG repeats with the risks of BPH and PCa by systematic review, and stratified their relationship according to the races of the patients. RESULTS: Based on the selection criteria, 4 of the 29 identified studies were included, with 485 cases of BPH, 767 cases of PCa, and 709 controls. There was no heterogeneity between the BPH and control groups, and no correlation between short CAG repeats and BPH after pooling the odds ratio (OR) effect size. Heterogeneity was found among the BPH, PCa and control groups. Random effects model suggested an association of short CAG repeats with the risk of PCa (OR(PCa/control) = 1.45, OR(PCa/BPH) = 1.86, OR(PCa/(BPH + control)) = 1.66), while subgroup analysis with racial stratification indicated inter-ethnic differences between the two. Begg and Egger bias analysis showed no significant publication bias. CONCLUSION: Shorter CAG repeats are positively correlated with the risk of PCa but not with that of BPH.

[Relationship of the positive rate of TRUS guided prostatic biopsies with routine diagnostic findings in detecting prostate cancer].

OBJECTIVE: To study the relationship of the positive rate of transrectal ultrasound (TRUS) guided prostatic biopsies in detecting prostate cancer with the findings of digital rectal examination (DRE), prostate imaging and measurement of the f/t PSA ratio. METHODS: We retrospectively analyzed the clinical findings of 365 patients with PSA of 4-10 microg/L who had received DRE, prostate imaging and measurement of the f/t PSA ratio. We performed TRUS guided prostatic biopsies and then analyzed the relationship between the biopsy results and previous findings. RESULTS: Of the 365 patients, 87 (23.84%) were found with prostate cancer by pathological biopsy, and 40 cases of prostate cancer (31.25% ) detected in 128 patients with positive findings in DRE, 26 cases of prostate cancer (37.68%) confirmed in 69 patients with positive findings in TRUS, and 59 cases of prostate cancer (55.14%) revealed in 107 patients with positive findings in MRI. The f/t PSA ratio was significantly lower in the malignant than in the benign cases (P < 0.01), and the area of f/t PSA ROC (0.725) was significantly higher than that of PSA ROC (0.542). CONCLUSION: DRE, prostate imaging and measurement of the f/t PSA ratio can improve the positive rate of prostate cancer detection, and therefore reduce unnecessary prostatic biopsies.

Carboxypeptidase E is a prognostic biomarker co-expressed with osteoblastic genes in osteosarcoma.

Osteosarcoma (OS) is a rare primary malignant bone tumor in adolescents and children with a poor prognosis. The identification of prognostic genes lags far behind advancements in treatment. In this study, we identified differential genes using mRNA microarray analysis of five paired OS tissues. Hub genes, gene set enrichment analysis, and pathway analysis were performed to gain insight into the pathway alterations of OS. Prognostic genes were screened using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, then overlapped with the differential gene dataset. The carboxypeptidase E (CPE) gene, found to be an independent risk factor, was further validated using RT-PCR and Gene Expression Omnibus (GEO) datasets. Additionally, we explored the specific expression of CPE in OS tissues by reanalyzing single-cell genomics. Interestingly, CPE was found to be co-expressed with osteoblast lineage cell clusters that expressed RUNX2, SP7, SPP1, and IBSP marker genes in OS. These results suggest that CPE could serve as a prognostic factor in osteoblastic OS and should be further investigated as a potential therapeutic target.

[Comparison of natural orifice transumbilical endoscopic surgery versus conventional laparoscopic surgery in renal cyst deroofing].

OBJECTIVE: To compare the safety and feasibility of natural orifice transumbilical endoscopic surgery (NOTES) versus conventional laparoscopic surgery in renal cyst deroofing. METHODS: From May 2010 to August 2011, 8 cases of renal cysts underwent cyst deroofing by the technique of NOTES (Triport) (group A) and 14 cases by conventional laparoscopic surgery (Group B) respectively. The data of patient age, cyst size, operative duration, estimated blood loss, intra-operative complications, drainage duration, post-operative pain score (VAPS) and post-operative hospital stay were recorded and analyzed. RESULTS: The average cyst sizes of groups A and B were 6.6 ± 2.4 and 7.0 ± 2.5 cm. There was no conversion to open surgery in neither groups and no conversion to standard laparoscopic surgery in group A. The operative duration, estimated blood volume, VAPS and post-operative hospital stay of both groups were 49 vs 35 min, 12 vs 10 ml, 0 vs 1 and 4 vs 5 days respectively. The drainage duration was 1 day for both groups. No severe complication, secondary hemorrhage or wound infection occurred in neither groups. As judged by both surgeons and patients, the post-operative cosmetic appearances of group A were better than those of group B. CONCLUSION: The cyst deroofing by NOTES is a safe and feasible option for the treatment of renal cysts. As compared with conventional laparoscopic surgery, NOTES may achieve better cosmetic effects with smaller wounds.

[5-alpha reductase inhibitors and prostate cancer prevention].

5-alpha reductase inhibitors decrease the level of dihydrotestosterone (DHT) by inhibiting 5-alpha reductase. Trials on 5-alpha reductase inhibitors in prostate cancer prevention showed that they could significantly decrease the incidence of prostate cancer, but meanwhile increase high-grade cases as well. Recent studies demonstrated that 5-alpha reductase inhibitors could reduce not only the prostate volume but also the volume of Gleason grade 3 prostate cancer, which made easier the detection of higher-grade prostate cancer in the second biopsy. 5-alpha reductase inhibitors could also increase the sensitivity of prostate biopsy in detecting prostate cancer, particularly that of a higher grade. The evidence we have obtained leads to the conclusion that 5-alpha reductase inhibitors do not increase the incidence of high-grade prostate cancer, but on the contrary help its earlier detection.

Mechanical Stimulation on Mesenchymal Stem Cells and Surrounding Microenvironments in Bone Regeneration: Regulations and Applications.

Treatment of bone defects remains a challenge in the clinic. Artificial bone grafts are the most promising alternative to autologous bone grafting. However, one of the limiting factors of artificial bone grafts is the limited means of regulating stem cell differentiation during bone regeneration. As a weight-bearing organ, bone is in a continuous mechanical environment. External mechanical force, a type of biophysical stimulation, plays an essential role in bone regeneration. It is generally accepted that osteocytes are mechanosensitive cells in bone. However, recent studies have shown that mesenchymal stem cells (MSCs) can also respond to mechanical signals. This article reviews the mechanotransduction mechanisms of MSCs, the regulation of mechanical stimulation on microenvironments surrounding MSCs by modulating the immune response, angiogenesis and osteogenesis, and the application of mechanical stimulation of MSCs in bone regeneration. The review provides a deep and extensive understanding of mechanical stimulation mechanisms, and prospects feasible designs of biomaterials for bone regeneration and the potential clinical applications of mechanical stimulation.

Development, In-Vitro Characterization and In-Vivo Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2.

The repair of large-volume bone defects (LVBDs) remains a great challenge in the fields of orthopedics and maxillofacial surgery. Most clinically available bone-defect-filling materials lack proper degradability and efficient osteoinductivity. In this study, we synthesized a novel biomimetically-precipitated nanocrystalline calcium phosphate (BpNcCaP) with internally incorporated bone morphogenetic protein-2 (BpNcCaP + BMP-2) with an aim to develop properly degradable and highly osteoinductive granules to repair LVBDs. We first characterized the physicochemical properties of the granules with different incorporation amounts of BMP-2 using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. We evaluated the cytotoxicity and cytocompatibility of BpNcCaP by assessing the viability and adhesion of MC3T3-E1 pre-osteoblasts using PrestoBlue assay, Rhodamine-Phalloidin and DAPI staining, respectively. We further assessed the in-vivo osteoinductive efficacy in a subcutaneous bone induction model in rats. In-vitro characterization data showed that the BpNcCaP + BMP-2 granules were comprised of hexagonal hydroxyapatite with an average crystallite size ranging from 19.7 to 25.1 nm and a grain size at 84.13 ± 28.46 nm. The vickers hardness of BpNcCaP was 32.50 ± 3.58 HV 0.025. BpNcCaP showed no obvious cytotoxicity and was favorable for the adhesion of pre-osteoblasts. BMP-2 incorporation rate could be as high as 65.04 ± 6.01%. In-vivo histomorphometric analysis showed that the volume of new bone induced by BpNcCaP exhibited a BMP-2 amount-dependent increasing manner. The BpNcCaP+50 µg BMP-2 exhibited significantly more degradation and fewer foreign body giant cells in comparison with BpNcCaP. These data suggested a promising application potential of BpNcCaP + BMP-2 in repairing LVBDs.

Analysis of Immune Gene Expression Subtypes Reveals Osteosarcoma Immune Heterogeneity.

BACKGROUND: Osteosarcoma (OS) patients have a poor response to immunotherapy due to the sheer complexity of the immune system and the nuances of the tumor-immune microenvironment. Methodology. To gain insights into the immune heterogeneity of OS, we identified robust clusters of patients based on the immune gene expression profiles of OS patients in the TARGET database and assessed their reproducibility in an independent cohort collected from the GEO database. The association of comprehensive molecular characterization with reproducible immune subtypes was accessed with ANOVA. Furthermore, we visualized the distribution of individual patients in a tree structure by the graph structure learning-based dimensionality reduction algorithm. RESULTS: We found that 87 OS samples can be divided into 5 immune subtypes, and each of them was associated with distinct clinical outcomes. The immune subtypes also demonstrated widely different patterns in tumor genetic aberrations, tumor-infiltrating, immune cell composition, and cytokine profiles. The immune landscape of OS uncovered the significant intracluster heterogeneity within each subtype and depicted a continuous immune spectrum across patients. CONCLUSION: The established five immune subtypes in our study suggested immune heterogeneity in OS patients and may provide optimal individual immunotherapy for patients exhibiting OS.

Correction: Anti-osteosarcoma effect of hydroxyapatite nanoparticles both in vitro and in vivo by downregulating the FAK/PI3K/Akt signaling pathway.

Correction for 'Anti-osteosarcoma effect of hydroxyapatite nanoparticles both in vitro and in vivo by downregulating the FAK/PI3K/Akt signaling pathway' by Renxian Wang et al., Biomater. Sci., 2020, 8, 4426-4437, DOI: 10.1039/D0BM00898B.

Therapeutic Potential of Circular RNAs in Osteosarcoma.

Osteosarcoma is the most common malignant bone tumor in children and adolescents. Multiagent chemotherapy, together with surgical removal of all detectable lesions, has improved the long-term survival rate to 65-70% in patients with localized osteosarcoma and to 25-30% in patients with metastatic osteosarcoma since the 1970s. However, the conventional strategy has not improved in recent decades. With accumulating knowledge of the natural circular RNA (circRNA) pathogenesis of osteosarcoma, the diagnostic and therapeutic potential of some circRNAs has been explored. Meanwhile, artificial circular RNAs have been designed as onco-microRNA inhibitors to exert antitumor functions. Therefore, natural and artificial circular RNAs, like other RNA counterparts, are attractive new classes of therapeutic molecules for the treatment of osteosarcoma. This review summarizes the latest progress in the relationship between circRNAs and the malignant phenotype of osteosarcoma and sheds light on the therapeutic potential of the two types of circular RNA in the clinic.

Building Osteogenic Microenvironments With Strontium-Substituted Calcium Phosphate Ceramics.

Bioceramics have experienced great development over the past 50 years. Modern bioceramics are designed to integrate bioactive ions within ceramic granules to trigger living tissue regeneration. Preclinical and clinical studies have shown that strontium is a safe and effective divalent metal ion for preventing osteoporosis, which has led to its incorporation in calcium phosphate-based ceramics. The local release of strontium ions during degradation results in moderate concentrations that trigger osteogenesis with few systemic side effects. Moreover, strontium has been proven to generate a favorable immune environment and promote early angiogenesis at the implantation site. Herein, the important aspects of strontium-enriched calcium phosphate bioceramics (Sr-CaPs), and how Sr-CaPs affect the osteogenic microenvironment, are described.

A polyethylenimine/salicylaldehyde modified cellulose Schiff base for selective and sensitive Fe3+ detection.

We describe a new solid-state colorimetric sensor synthesized by micro-crystalline cellulose (MCC) in the presence of polyethylenimine (PEI) and salicylaldehyde (SA) via an oxidation process and two successive Schiff base reactions. The formation of the Fe3+ complex led to color change detectable by eye, as well as an absorption peak at 501 nm causing fluorescence quenching. The signal was linear with the concentration ranging from 4 to 20 ppm; the detection limit is 0.01 ppm, making this a sensitivity and reliable monitoring platform for Fe3+ detection. Orbital electron distribution and computational studies were also carried out using density functional theory (DFT) to better supplement the sensor's detection performance. Finally, the sensing mechanism is discussed in detail.