Hypoxia-Responsive Tetrameric Supramolecular Polypeptide Nanoprodrugs for Combination Therapy.

Despite the intense progress of photodynamic and chemotherapy, however, they cannot prevent solid tumor invasion, metastasis, and relapse, along with inferior efficacy and severe side effects. The hypoxia-responsive nanoprodrugs integrating photodynamic functions are highly sought to address the above-mentioned problems and overcome the tumor hypoxia-reduced efficacy. Herein, a hypoxia-responsive tetrameric supramolecular polypeptide nanoprodrug (SPN-TAPP-PCB4) is constructed from the self-assembly of tetrameric porphyrin-central poly(l-lysine-azobenzene-chlorambucil) (TAPP-(PLL-Azo-CB)4) and an anionic water-soluble [2]biphenyl-extended-pillar[6]arene (AWBpP6) via the synergy of hydrophobic, π-π stacking, and host-guest interactions. Upon laser irradiation, the central TAPP can convert oxygen to generate single oxygen (1 O2 ) to kill tumor cells. Furthermore, under the acidic and PDT-aggravated hypoxia tumor cell microenvironment, SPN-TAPP-PCB4 is rapidly disassembled, and then efficiently releases activated CB through the hypoxic-responsive cleavage of azobenzene linkages. Both in vitro and in vivo biological studies showcase synergistic cancer-killing actions between photodynamic therapy (PDT) and chemotherapy (CT) with negligible toxicity. Consequently, this supramolecular polypeptide nanoprodrug offers an effective strategy to design a hypoxia-responsive nanoprodrug for a potential combo PDT-CT transition.

Generation and characterization of patient-derived xenografts from patients with osteosarcoma.

BACKGROUND: Standard therapy of osteosarcoma (OS) rests on cytotoxic regimes, which dramatically limits the further improvement in the prognosis of patients with OS. Preclinical models of OS are extremely urgent to break this impasse. MATERIALS AND METHODS: Here, we describe our experience of developing patient-derived tumor xenografts (PDXs) using surgical samples from patients with OS. All the xenografts growing subcutaneously in mice will be identified pathologically and genetically. Furthermore, we explored the consistency of the drug sensitivity between the PDX models and corresponding patients against specific regimens. RESULTS: We generated nine OS PDXs from 21 surgical resections of primary OS tumors, with an engraftment rate of 42.9 %. Morphological and immunohistochemical (SATB2, MDM2, CDK4, and Ki67) studies and whole-exome sequencing showed a remarkable similarity between the patient's tumor and corresponding PDX, which was maintained over several passages in mice. A therapeutic combination of Pirarubicin and Cisplatin was tested against two OS PDX models, in which the corresponding patient was insensitive and sensitive to the regimen, respectively. CONCLUSION: The panel of OS PDX models faithfully mirrored morphologic and genetic features of OS, representing reliable models to test therapeutic approaches.

Stattic sensitizes osteosarcoma cells to epidermal growth factor receptor inhibitors via blocking the interleukin 6-induced STAT3 pathway.

Osteosarcoma (OS), the most common malignant bone tumor with high metastatic potential, frequently affects children and adolescents. Epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors exhibit encouraging anti-tumor activity for patients with solid tumors, whereas their effects on OS remain controversial. In the present study, we aimed to elucidate the anti-tumor activity of gefitinib for OS, as well as to explore the underlying mechanisms. Gefitinib inhibits cell viability, tumor growth, cell migration, and invasion and promotes cell apoptosis and G1 cycle arrest in OS at a relatively high concentration via suppressing the PI3K/Akt and ERK pathways. However, gefitinib treatment results in the feedback activation of signal transducer and activator of transcription 3 (STAT3) induced by interleukin 6 (IL-6) secretion. Combined treatment with gefitinib and stattic, an inhibitor for STAT3 phosphorylation, engenders more evident inhibitory effects on cell proliferation, migration, and invasion and promotive effects on cell apoptosis and G1 phase arrest in OS, compared with the single exposure to gefitinib or stattic. Western blot analysis demonstrates that stattic treatment in gefitinib-treated OS abrogates the IL-6-induced STAT3 activation and subsequently further restrains the activities of EGFR, Akt, and ERK pathways in tumor cells. This study confirms that the EGFR inhibitor of gefitinib has moderate anti-tumor effects on OS through IL-6 secretion-mediated STAT3 activation. Additional administration of stattic in EGFR-targeted therapies may contribute to improve the efficacy for OS.

Corrigendum: NLRP3 Overexpression Associated With Poor Prognosis and Presented as an Effective Therapeutic Target in Osteosarcoma.

[This corrects the article DOI: 10.3389/fphar.2021.724923.].

Inhibition of BUB1 suppresses tumorigenesis of osteosarcoma via blocking of PI3K/Akt and ERK pathways.

Osteosarcoma (OS) is a primary malignant bone tumour that mainly affects teenagers, with patients displaying poor prognosis. Budding uninhibited by benzimidazoles 1 (BUB1), a type of serine/threonine kinase that is linked to pro-tumorigenic phenomena, has not been well studied in OS. Hence, this study aimed to explore the role of BUB1 in OS. The expression of BUB1 in OS specimens and cell lines was assessed using immunohistochemistry and Western blot analysis. Univariate and multivariate analyses were applied to evaluate the impact of BUB1 on patient survival. Cell counting kit-8, wound-healing and Transwell assays, as well as flow cytometry, were used to investigate the influence of BUB1 inhibition on OS in vitro. Moreover, a tumour xenograft model was established to investigate the in vivo effect of BUB1 inhibition on OS tumour growth. Results showed that BUB1 was overexpressed in OS specimens and cell lines. Furthermore, BUB1 overexpression was closely associated with the poor clinical outcomes of patients with OS. Inhibition of BUB1 markedly suppressed cell proliferation and tumour growth, cell migration, invasion and induced cell apoptosis of OS by blocking the PI3K/Akt and ERK signalling pathways. Thus, our study suggested that overexpression of BUB1 protein contributed to poor survival of OS patients and that inhibition of BUB1 resulted in considerable anti-tumour activity associated with proliferation, migration, invasion and apoptosis of OS.

NLRP3 Overexpression Associated With Poor Prognosis and Presented as an Effective Therapeutic Target in Osteosarcoma.

Despite the development of diagnostic and treatment strategies, the survival outcome of patients with osteosarcoma remains poor. Nod-like receptor protein 3 (NLRP3) plays a crucial role in the inflammasome pathway, which is related to the progression of various tumors. However, the effect of NLRP3 on osteosarcoma has not yet been well explored. Our study aimed to investigate the role of NLRP3 in the malignant biological behavior of osteosarcoma as well as its therapeutic value. Immunohistochemistry was applied to investigate the NLRP3 expression in osteosarcoma and osteochondroma specimens. Cell Counting Kit-8, colony formation, wound healing, transwell, and flow cytometry assays were used to explore the contribution of NLRP3 to the proliferation, migration, invasion, apoptosis and cell cycle distribution of osteosarcoma cells in vitro. Western blot was performed to evaluate the expression of NLRP3 and the related proteins in osteosarcoma cell lines after the blockade of NLRP3 using CY-09 and lentivirus intervention. Furthermore, tumor formation assay was used to analyze the effect of NLRP3 on the growth of osteosarcoma in vivo. The results showed that the NLRP3 protein was overexpressed in osteosarcoma, which was independently correlated with the poor prognosis of patients. Moreover, NLRP3 suppression by the inhibitor of CY-09 or lentivirus-induced gene knockdown inhibited the cell proliferation, migration, invasion and promoted the cell apoptosis and G1 cell cycle arrest in osteosarcoma via targeting the inflammasome pathway. Our in vivo results confirmed that the inhibition of NLRP3 suppressed the tumor formation of osteosarcoma. In conclusion, NLRP3 may be regarded as an independent prognostic biomarker and a potential therapeutic target for osteosarcoma.

Hypoxia increases the expression of stem cell markers in human osteosarcoma cells.

Osteosarcoma (OS) is the most common primary malignant tumor of bone. It is a common phenomenon that osteosarcoma cells have a hypoxic microenvironment. Hypoxia can dedifferentiate cells of several malignant tumor types into stem cell-like phenotypes. However, the role of hypoxia in stemness induction and the expression of cancer stem cell (CSC) markers in human osteosarcoma cells has not been reported. The present study examined the effects of hypoxia on stem-like cells in the human osteosarcoma MNNG/HOS cells. Under the incubation with 1% oxygen, the expression of CSCs markers (Oct-4, Nanog and CD133) in MNNG/HOS cells were increased. Moreover, MNNG/HOS cells cultured under hypoxic conditions were more likely to proliferate into spheres and resulted in larger xenograft tumor. Hypoxia also increased the mRNA and protein levels of hypoxia-inducible factor (HIF)-1α. Then rapamycin was used, which has been shown to lower HIF-1α protein level, to inhibit the hypoxic response. Rapamycin suppressed the expression of HIF-1α protein and CSCs markers (Oct4, Nanog and CD133) in MNNG/HOS cells. In addition, pretreatment with rapamycin reduced the efficiency of MNNG/HOS cells in forming spheres and xenograft tumors. The results demonstrated that hypoxia (1% oxygen) can dedifferentiate some of the MNNG/HOS cells into stem cell-like phenotypes, and that the mTOR signaling pathway participates in this process via regulating the expression of HIF-1α protein.

Epidermal growth factor receptor promotes tumor progression and contributes to gemcitabine resistance in osteosarcoma.

Osteosarcoma (OS) is the most common type of primary malignant tumors that originate in the bone. Resistance to chemotherapy confers a poor prognosis on OS patients. Dysregulation of the epidermal growth factor receptor (EGFR) signaling has been reported in sarcomas. However, the functional contribution of EGFR hyperactivation to the tumor biology and chemoresistance remains largely unexplored in OS. In this study, we aimed to investigate the role of EGFR in OS progression and in the response of OS to gemcitabine treatment. The EGFR expression was found to be upregulated in fibroblastic OS cell lines. EGFR knockdown suppressed OS cell proliferation, migration, and invasion in vitro and tumor formation in vivo. Conversely, EGFR overexpression promoted the growth and motility of OS cells. In terms of mechanism, the levels of phospho-Akt and phospho-ERK were decreased upon EGFR knockdown but increased as a result of EGFR overexpression, implying a possible involvement of PI3K/Akt and ERK pathways in mediating the effects of EGFR on OS cells. Moreover, the level of phospho-EGFR was increased in OS cells when exposed to gemcitabine treatment. A more profound proliferative inhibition and a higher rate of apoptosis were obtained in OS cells via inducing cell cycle arrest at G1 phase upon gemcitabine treatment combined with EGFR knockdown, as compared to gemcitabine alone. On the contrary, EGFR overexpression counteracted the growth-inhibiting and pro-apoptotic effects of gemcitabine in OS cells. The present study suggests that EGFR promotes tumor progression and contributes to gemcitabine resistance in OS.

Clinicopathological and prognostic value of NADPH oxidase 2 (NOX2) in primary osteosarcoma.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor, particularly among children and adolescents, and the prognosis of osteosarcoma patients remains poor. The NADPH oxidase 2 (NOX2) has been found over-expressed in several human cancers, and closely associated with poor prognosis. Meanwhile the role of NOX2 in osteosarcoma patients has not been reported. This study aimed to investigate the clinicopathological and prognostic significance of NOX2 in osteosarcoma patients. METHODS: Immunohistochemistry (IHC), western blot (WB) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression of NOX2 in 55 primary osteosarcoma specimens and in 20 non-neoplastic bone tissue specimens. The correlations between NOX2 expression and clinicopathological parameters were analysed by using the χ2 test or Fisher's exact test. Disease free survival and overall survival of osteosarcoma patients were assessed by using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: NOX2 was over-expressed significantly in osteosarcoma compared with that in non-neoplastic bone tissue, and correlated with progression free survival (P < 0.001) and overall survival (P < 0.001). The over-expression of NOX2 was associated with tumor size (P < 0.001), tumor location (P < 0.001). The Cox analysed shown that the over-expression of NOX2 was predicted to be worse PFS (hazard ratio (HR) = 4.10, P = 0.004) and OS (hazard ratio (HR) = 3.50, P = 0.010) time in osteosarcoma patients. CONCLUSIONS: The results of our study suggest that the over-expression of NOX2 is related to adverse clinical outcome, and can be viewed as an independent prognostic marker in osteosarcoma. Further research is required to verify the predictive value of NOX2 in osteosarcoma patients.

[Treatment and influencing factors of infection after limb salvage surgery for malignant tumor around knee joint].

OBJECTIVE: To summarize the experience in the treatment of infection after limb salvage surgery for malignant tumor around knee joint, and explore the risk factor related to infection after limb salvage surgery. METHODS: A clinical data of 212 patients with malignant tumor around the knee joint underwent limb salvage surgery between January 2008 and December 2017 were retrospectively analyzed. Among them, 14 cases had infection after limb salvage surgery. Two cases of acute infection were treated with sensitive antibiotics; 12 cases of chronic infection were treated with debridement and antibiotic bone cement occupying device implantation in the first stage, and prosthesis revision (8 cases), knee joint fusion (2 cases), or amputation (2 cases) in the second stage after infection control. The age, gender, preoperative chemotherapy cycle, bone marrow suppression, serum albumin, hemoglobin, operation time, postoperative drainage time, and blood transfusion volume were analyzed to screen the risk factors related to infection after limb salvage surgery. The infection and tumor recurrence were observed, and the limb function was evaluated by Enneking scoring system. RESULTS: The univariate analysis showed that the preoperative chemotherapy cycle, bone marrow suppression, operation time, and postoperative drainage time were the influencing factors of postoperative infection ( P<0.05). Multivariate analysis showed that the operation time, preoperative chemotherapy cycle, and postoperative drainage time were risk factors of postoperative infection ( P<0.05). Among the 14 patients, 1 patient died of traffic accident at 6 months after the second stage operation, and 13 patients were followed up 12.2-48.0 months (mean, 19.9 months). Two cases of acute infection cured. Among the 11 patients with chronic infection, 2 cases of subluxation of the antibiotic bone cement occupying device after the first stage operation occurred; 9 cases of infection cured and 2 cases recurred. At 12 months after operation, except 1 case died by accident, the Enneking scores of the other 13 patients were 12-26, with an average of 20. At last follow-up, 1 case of lung metastasis was still alive, and no tumor metastasis or recurrence was found in the rest. CONCLUSION: The time of limb salvage surgery, preoperative chemotherapy cycle, and drainage time after limb salvage surgery are the risk factors of infection after limb salvage surgery. Early etiological examination and drug sensitivity test is the key to the treatment of infection. One-stage debridement combined with antibiotic bone cement occupying device can effectively cure infection and save patients' limbs.

A novel mitochondria-targeted phosphorescence probe for hypochlorite ions detection in living cells.

Monitoring hypochlorite anion (ClO-) in living cells is particularly meaningful and valuable, because over-exposure of the ClO- may cause a potential health hazard towards animals and humans. Considering the special structure and properties of the gemini surfactant, a novel amphiphilic gemini-iridium complex Ir[(ppy-iso)2(bpy-tma2Br2)] (Ir-iso) with isoniazide as a recognition site for ClO- was designed. The Ir-iso possessed an excellent water-solubility as well as a strong ClO- binding capacity, as revealed from the rapid response of emission signal towards ClO-. It was worth noting that such probe had a highly-specific selectivity with a low detection limit (20.5 nM) and was suitable in physiological environment. The cell viability assay, cell imaging, and co-location studies further proved that the Ir-iso had little cytotoxicity and was specifically localized in the mitochondria of breast cancer cells, being a promising candidate of chemo-sensor to detect the endogenous ClO- in living cells.

Clinicopathological and prognostic values of ErbB receptor family amplification in primary osteosarcoma.

Osteosarcoma is a malignant bone tumor with extremely high invasion, metastasis and mortality. The prognosis of patients with osteosarcoma remains poor. The ErbB receptor family was found to be overexpressed in human cancers and associated with poor prognosis. However, the role of ErbB receptor family in osteosarcoma has not been fully understood. The present study aimed to investigate the clinicopathological and prognostic significances of ErbB receptors in primary osteosarcoma. Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) were used to detect the protein and gene expression of ErbB receptors in 60 primary osteosarcoma specimens and 30 non-neoplastic bone tissues. WB and RT-qPCR analyses showed that the protein and mRNA expression levels of EGFR, ErbB3 and ErbB4 in osteosarcoma specimens were significantly higher than those in non-neoplastic bone tissues. Seventeen (28.33%), 15 (25.00%) and 15 (25.00%) osteosarcoma specimens presented with amplification of EGFR, ErbB3 and ErbB4 gene, respectively, which were significantly higher compared with non-neoplastic bone tissues. The amplification of ErbB3 and ErbB4 in osteosarcoma was associated with advanced surgical stage. The amplification of EGFR, ErbB3, ErbB4 and the co-amplification of EGFR-ErbB3, EGFR-ErbB4, ErbB3-ErbB4 was linked with poor response to chemotherapy and distant metastasis. The amplification of EGFR, ErbB3 and ErbB4, as well as their co-amplification demonstrated independent prognostic values for reduced survival time of osteosarcoma patients and may serve as potential therapeutic targets for osteosarcoma patients in the future.

Anterior Cervical Surgery for the Treatment of Hirayama Disease.

OBJECTIVE: To provide a quantitative assessment of clinical outcomes of anterior cervical surgery for patients with Hirayama disease. METHODS: Nineteen patients undergoing anterior cervical surgery were retrospectively collected, and preoperative and postoperative clinical and radiographic data were compared. RESULTS: All patients had a mean follow-up time of 72.5 ± 30.6 months. Tremor in 6 of 14 patients and cold paralysis in 8 patients were resolved after operation. Grip strength of upper extremities was significantly improved (preoperative 15.67 ± 2.74 kg vs. postoperative 19.82 ± 2.89 kg, P < 0.001). Postoperative cervical lordosis was significantly increased to 6.41 ± 4.39 mm from 2.70 ± 4.61 mm (P < 0.001). The overall range of cervical flexed motion was significantly decreased (preoperative 33.10° ± 10.60° vs. postoperative 13.55° ± 6.69°, P < 0.001), with segmental range of C5-6 (preoperative 12.52° ± 7.13° vs. postoperative 7.04° ± 3.75°, P = 0.002) and C6-7 (preoperative 9.01° ± 5.01° vs. postoperative 5.73° ± 2.74°, P = 0.014) contributing significantly to the improvement. Postoperative angle mobility of C3-4 to C6-7 was significantly decreased (P < 0.001). Postoperative neutral magnetic resonance imaging showed the transverse area of spinal cord of C6 (P = 0.016) and C7 (P = 0.021) was significantly increased. CONCLUSIONS: Anterior cervical surgery can provide clinical efficacy and imaging improvement, including reduced range of cervical flexed motion and angle mobility of lower cervical spine and increased cervical lordosis and spinal cord area.

A highly sensitive peptide-based biosensor using NiCo2O4 nanosheets and g-C3N4 nanocomposite to construct amplified strategy for trypsin detection.

Here, a simple electrochemical biosensor was proposed based on the specific recognition between trypsin and peptide. Initially, NiCo2O4-PAMAM nanocomposite was casted on the bare electrode to achieve the electrochemical signal amplification in 0.1 mM [Ru(NH3)6]3+ solution owing to the great electronic conductivity and high electrochemical activity induced by the special structure of NiCo2O4 nanosheets (Ni3+ cations in octachedral sites of the Co3O4). Subsequently, a declined electrochemical signal was obtained when g-C3N4 labeled peptide composites were anchored on the electrode. However, after trypsin was added into solution and incubated with the biosensor, the electrochemical signal was re-promoted. Therefore, the as-synthesized biosensor could realize the sensitive detection of trypsin by virtue of the specific recognition between trypsin and peptide. As a result, the developed peptide-based exhibited a linear range from 10-10 to 10-4 mg mL-1 with an ultralow detection limit of 10-10 mg mL-1, providing sensitive analytical performance and acceptable application potential in clinical test and disease diagnosis due to its high stability, excellent selectivity, acceptable reproducibility and accurate signal output.

The clinical significance of the Ezrin gene and circulating tumor cells in osteosarcoma.

PURPOSE: The aim of this study was to investigate the clinical significance of circulating tumor cells (CTCs) in the peripheral blood of an osteosarcoma and the Ezrin gene expressed in CTCs. PATIENTS AND METHODS: CTC enrichment was done with CanPatrol™ CTC enrichment technique in 41 patients with osteosarcoma. The characterization of CTCs was performed using a multiple messenger RNA in situ analysis (MRIA). The expression of the Ezrin gene in CTCs was detected by RNA probe technology. The correlations of CTC counts, cell type and the expression level of the Ezrin gene with clinical stage and metastasis of osteosarcoma were analyzed using SPSS 16.0 software. RESULTS: The CTC counts correlated significantly with Enneking stage (P<0.001). The ratio of mesenchymal CTCs correlated with the distant metastases (P<0.001). Ezrin gene expression in CTCs correlated significantly with distant metastases (χ2=152.51, P=0.000). CONCLUSION: The ratio of mesenchymal CTCs in the peripheral blood of osteosarcoma correlates with distant metastases. High expression of Ezrin gene in CTCs correlates with distant metastases.

Exosomes mediated pentose phosphate pathway in ovarian cancer metastasis: a proteomics analysis.

Epithelial ovarian cancer is the most lethal gynecological malignancies for readily metastasis. Exosomes have played an influential role in carcinogenicity and cancer progression. Our aim is to discover exosome-related mechanisms in ovarian cancer progress and explore potential diagnostic biomarkers and therapeutic targets of ovarian cancer. We initially presented the proteomic profiles of exosomes derived from two late-stage ovarian cell lines, OVCA429 and HO8910PM. A total of 2940 exosomal proteins were recorded by MS. FunRich appropriately processed these exosomal proteins, manifesting some superiority in contrast to Blast2go. Moreover, we demonstrated the pentose phosphate pathway was a dominant mechanism in exosome mediated intracellular communication. Glucose-6-phosphate dehydrogenase, transketolase and transaldolase 1, three key enzymes regulated pentose phosphate pathway, were all marked in the same exosomal parts of proteins between two ovarian cell lines. Moreover, these key proteins might become diagnostic, prognostic biomarkers and therapeutic targets of ovarian cancer.

[Total hip arthroplasty for treatment of Crowe type IV congenital dysplasia of hip with dislocation in adults].

OBJECTIVE: To study the effectiveness and acetabular prosthesis selection of the total hip arthroplasty (THA) for Crowe type IV congenital dysplasia of the hip with dislocation in adults. METHODS: Between June 2008 and May 2012, 8 adult patients (8 hips) with Crowe type IV congenital dysplasia of the hip with dislocation underwent THA. They were all female, aged 20-35 years with a mean age of 25 years. The left hip was involved in 5 cases and the right hip in 3 cases. The Harris score of involved hip was 53.9 +/- 6.6. The shortened length of involved extremity was 4-6 cm (mean, 4.8 cm). The X-ray films showed complete dislocation in all cases. The acetabular prosthesis with diameter of 42-44 mm and S-ROM femoral prosthesis were used in THA. RESULTS: The incisions healed by first intention. There was no hip dislocation events and sciatic nerve injury during the follow-up. Femoral nerve injury occurred in 1 case and asymptomatic venous thrombosis of the leg muscle occurred in 2 cases. All the patients were followed up 1-5 years (mean, 3 years). All cases showed obvious improvement of claudication and could restore to work. At 6 months after operation, the mean length difference between affected and contralateral extremities was 0.4 cm (range, 1.0-0.6 cm); the Harris score was significantly increased to 87.6 +/- 0.3 (t = 1.77, P = 0.00). The X-ray films showed that all cases got bony union at 3-6 months after operation and stable interface between acetabular prosthesis and bone. No revision was involved during the follow-up. CONCLUSION: THA with small acetabular cup and subtrochanteric osteotomy is an effective method in the treatment of Crowe type IV congenital dysplasia of the hip with dislocation in adults. The early effectiveness is satisfactory. The long-term survival rate of prosthesis needs to be followed up.

[Extra-large uncemented acetabular components for hip revision].

OBJECTIVE: To investigate the early-term effectiveness of extra-large uncemented acetabular components for hip revision in the treatment of extensive acetabular bone defect. METHODS: Between September 2008 and May 2012, 13 patients (13 hips) with extensive acetabular bone defect underwent first hip revision using extra-large uncemented acetabular components (Jumbo cup). The diameter of Jumbo cup was larger than or equal to 64 mm for male and 60 mm for female. There were 4 males and 9 females with an average age of 64.7 years (range, 58-84 years). The period from primary arthroplasty to revision was 3-16 years (mean, 9.6 years). According to Paprosky classification, acetabular bone defect was rated as stage IIA in 2 cases, as stage IIB in 5 cases, as stage IIC in 4 cases, and as stage IIIA in 2 cases. The preoperative vertical distance from the center of involved femoral head to interteardrop line was (21.2 +/- 6.1) mm longer than that of normal side. The Harris score and the rotation center of hip were evaluated preoperatively and postoperatively. RESULTS: Healing of incision by first intention was obtained in all patients, and no complication of dislocation, infection, and injury of sciatic nerve or femoral nerve occurred. The duration of follow-up ranged from 13 to 40 months (mean, 23.5 months). Partial or complete pain relief was achieved in all patients. The other patients could walk independently and restored to their routine jobs except for 1 case of hemiplegia caused by acute cerebral infarction at 3 months after surgery. In 5 patients with bone implantation, with the prolonging follow-up, the allograft could integrate with the host bone without absorption, and the bone fusion time was 9-35 months (mean, 14.5 months). At last follow-up, the X-ray films revealed that the vertical distance from the center of involved femoral head to interteardrop line was (6.0 +/- 3.1) mm longer than that of normal side, which was significantly reduced when compared with preoperative value (t=11.13, P=0.00). No periprosthetic transparent region, prosthesis displacement, or screw breakage occurred. The Harris score was significantly increased from 30.4 +/- 8.8 preoperatively to 85.1 +/- 3.2 at last follow-up (t-22.11, P=0.00). CONCLUSION: The application of extra-large uncemented acetabular components could be an effective technique for the reconstruction of extensive acetabular bone defect, and gain a good early-term effectiveness. The long-term survival rate of prostheses needs to be followed up.