Idiopathic tenosynovitis of the wrist with multiple rice bodies: A case report and review of literature.

BACKGROUND: Multiple rice bodies in the wrist is a rare disorder that requires surgery, and there are still many uncertainties regarding its diagnosis and treatment. CASE SUMMARY: We described a rare case of chronic idiopathic tenosynovitis with rice bodies of the wrist in a 71-year-old man and reviewed similar topics in the literature. A total of 43 articles and 61 cases were included in the literature review. Our case had a usual presentation: it was similar to those in the literature. The affected population was mainly older adults, with an average age of 59.43 (range, 3 to 90) years. The male-to-female ratio was 1.54:1 (37/24).Most of them showed limited swelling and pain, only 23.0% had carpal tunnel symptoms, and the average disease duration was 18.03 (0.5-60) mo. Wrist flexor tendon sheath involvement was the most common (95.1%, 58/61), and only 3 cases had extensor tendon sheath involvement.The main causes were tuberculosis (34.4%, 21/61), non-tuberculous mycobacteria (24.6%, 15/61), idiopathic tenosynovitis (31.1%, 19/61), and others (9.84%, 6/61). There were 10 patients with recurrences; in 6 of them, were due to non-tuberculous mycobacterial infections. CONCLUSION: We reported a case of wrist idiopathic tenosynovitis with rice body formation, and established a clinical management algorithm for wrist tenosynovitis with rice bodies, which can provide some reference for our clinical diagnosis and treatment. The symptoms of rice-body bursitis of the wrist are insidious, nonspecific, and difficult to identify. The aetiology is mainly idiopathic tenosynovitis and mycobacterial (tuberculosis or non-tuberculous) infections; the latter are difficult to treat and require long-duration systemic combination antibiotic therapies. Therefore, before a diagnosis of idiopathic tenosynovitis is made, we must exclude other causes, especially mycobacterial infections.

Targeting an Autocrine Regulatory Loop in Cancer Stem-like Cells Impairs the Progression and Chemotherapy Resistance of Bladder Cancer.

PURPOSE: Cancer stem-like cells (CSCs) contribute to bladder cancer chemotherapy resistance and progression, but the associated mechanisms have not been elucidated. This study determined whether blocking an autocrine signaling loop in CSCs improves the therapeutic effects of cis-platinum on bladder cancer. EXPERIMENTAL DESIGN: The expression of the epithelial marker OV6 and other markers in human bladder cancer specimens was examined by IHC. The CSC properties of magnetic-activated cell sorting (MACS)-isolated OV6+ and OV6- bladder cancer cells were examined. Molecular mechanisms were assessed through RNA-Seq, cytokine antibody arrays, co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP) and other assays. An orthotopic bladder cancer mouse model was established to evaluate the in vivo effects of a YAP inhibitor (verteporfin) and a PDGFR inhibitor (CP-673451) on the cis-platinum resistance of OV6+ CSCs in bladder cancer. RESULTS: Upregulated OV6 expression positively associated with disease progression and poor prognosis for bladder cancer patients. Compared with OV6- cells, OV6+ bladder cancer cells exhibited strong CSC characteristics, including self-renewal, tumor initiation in NOD/SCID mice, and chemotherapy resistance. YAP, which maintains the stemness of OV6+ CSCs, triggered PDGFB transcription by recruiting TEAD1. Autocrine PDGF-BB signaling through its receptor PDGFR stabilized YAP and facilitated YAP nuclear translocation. Furthermore, blocking the YAP/TEAD1/PDGF-BB/PDGFR loop with verteporfin or CP-673451 inhibited the cis-platinum resistance of OV6+ bladder cancer CSCs in an orthotopic bladder cancer model. CONCLUSIONS: OV6 could be a helpful indicator of disease progression and prognosis for patients with bladder cancer, and targeting the autocrine YAP/TEAD1/PDGF-BB/PDGFR loop might serve as a remedy for cis-platinum resistance in patients with advanced bladder cancer.

Blocking the Feedback Loop between Neuroendocrine Differentiation and Macrophages Improves the Therapeutic Effects of Enzalutamide (MDV3100) on Prostate Cancer.

Purpose: Androgen deprivation therapy (ADT), including enzalutamide, induces resistance in prostate cancer; ADT resistance is associated with neuroendocrine differentiation (NED) and tumor-associated macrophages (TAM). This study aimed to investigate the association between enzalutamide-induced NED and TAMs and its mechanism.Experimental Design: The association between enzalutamide-induced NED and TAMs was investigated by IHC using prostate cancer tissues, enzalutamide-resistant mouse xenografts, and a coculture system. The underlying mechanisms were assessed using in vitro cytokine antibody arrays, ELISAs, chromatin immunoprecipitation, and other methods. An orthotopic prostate cancer mouse model was established to evaluate the in vivo effects of combined IL6 receptor (IL6R) and high mobility group box 1 (HMGB1) inhibition on enzalutamide resistance.Results: High CD163 expression was observed in ADT-treated prostate cancer or castration-resistant prostate cancer (CRPC) tissues with high levels of neuron-specific enolase (NSE) and chromogranin A (CHGA) and in enzalutamide-resistant xenografts, indicating the crucial roles of NED and TAMs in enzalutamide resistance. Specifically, enzalutamide-induced HMGB1 expression facilitated TAM recruitment and polarization and drove NED via ß-catenin stabilization. HMGB1-activated TAMs secreted IL6 to augment enzalutamide-induced NED and directly promote HMGB1 transcription via STAT3. Finally, inhibition of the IL6/STAT3 pathway by tocilizumab combined with HMGB1 knockdown inhibited enzalutamide-induced resistance in an orthotopic prostate cancer mouse model.Conclusions: Enzalutamide elevates HMGB1 levels, which recruits and activates TAMs. Moreover, IL6 secreted by HMGB1-activated TAMs facilitates the enzalutamide-induced NED of prostate cancer, forming a positive feedback loop between NED in prostate cancer and TAMs. The combined inhibition of IL6R and HMGB1 may serve as a new treatment for enzalutamide resistance in patients with advanced or metastatic prostate cancer. Clin Cancer Res; 24(3); 708-23. ©2017 AACR.

Reciprocal Network between Cancer Stem-Like Cells and Macrophages Facilitates the Progression and Androgen Deprivation Therapy Resistance of Prostate Cancer.

Purpose: Cancer stem-like cells (CSC) contribute to the progression and androgen deprivation therapy (ADT) resistance of prostate cancer. As CSCs depend on their specific niche, including tumor-associated macrophages (TAM), elucidating the network between CSCs and TAMs may help to effectively inhibit the progression and ADT resistance of prostate cancer.Experimental Design: The underlying intracellular mechanism that sustains the stem-like characteristics of CSCs in prostate cancer was assessed via RNA sequencing, co-immunoprecipitation, chromatin immunoprecipitation, and other assays. A coculture system and cytokine antibody arrays were used to examine the interaction network between CSCs and TAMs. In addition, an orthotopic prostate cancer model was established to evaluate the in vivo effects of the combined targeting of CSCs and their interaction with TAMs on ADT resistance.Results: Autophagy-related gene 7 (ATG7) facilitated the transcription of OCT4 via ß-catenin, which binds to the OCT4 promoter, promoting CSC characteristics in prostate cancer, including self-renewal, tumor initiation, and drug resistance. In addition, CSCs remodeled their specific niche by educating monocytes/macrophages toward TAMs, and the CSC-educated TAMs reciprocally promoted the stem-like properties of CSCs, progression and ADT resistance of prostate cancer via IL6/STAT3. Furthermore, the combined targeting of CSCs and their interaction with TAMs by inhibiting ATG7/OCT4 and IL6 receptor effectively ameliorated ADT resistance in an orthotopic prostate cancer model.Conclusions: Targeting CSCs and their niche may prove to be a more powerful strategy than targeting CSCs alone, providing a rational approach to ameliorating ADT resistance in prostate cancer. Clin Cancer Res; 24(18); 4612-26. ©2018 AACR.

Preparation and characterization of genipin-crosslinked rat acellular spinal cord scaffolds.

The feasibility of rat acellular spinal cord scaffolds for tissue engineering applications was investigated. Fresh rat spinal cords were decellularized and crosslinked with genipin (GP) to improve their structural stability and mechanical properties. The GP-crosslinked spinal cord scaffolds possessed a porous structure with an average pore diameter of 31.1 µm and a porosity of 81.5%. The resultant scaffolds exhibited a water uptake ratio of 229%, and moderate in vitro degradation rates of less than 5% in phosphate-buffered saline (PBS) and slightly more than 20% in trypsin-containing buffer, within 14 days. The ultimate tensile strength and elastic modulus of GP-crosslinked spinal cord scaffolds were determined to be 0.193±0.064 MPa and 1.541±0.082 MPa, respectively. Compared with glutaraldehyde (GA)-crosslinked acellular spinal cord scaffolds, GP-crosslinked scaffolds demonstrated similar microstructure and mechanical properties but superior biocompatibility as indicated by cytotoxicity evaluation and rat mesenchymal stem cell (MSC) adhesion behavior. Cells were able to penetrate throughout the crosslinked scaffold due to the presence of an interconnected porous structure. The low cytotoxicity of GP facilitated cell proliferation and extracellular matrix (ECM) secretion in vitro on the crosslinked scaffolds over 7 days. Thus, these GP-crosslinked spinal cord scaffolds show great promise for tissue engineering applications.