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Background: Surgical site infection (SSI) is a common complication following orthopedic implantation. We developed an iodine coating for titanium implants to reduce implant-related infections and conducted a prospective clinical study to evaluate the efficacy and potential drawbacks of iodine-supported implants. Patients and methods: Between July 2008 and July 2017, 653 patients (377 male and 27 female patients; mean age, 48.6) with postoperative infection or a compromised status were treated using iodine-loaded titanium implants. The mean follow-up period was 41.7 months. In 477 patients, iodine-supported implants were used to prevent infection and in 176 patients, to treat active infection (one-stage surgery, 89 patients; two-stage surgery, 87 patients). In the limbs and pelvis, the primary diagnoses included the following: 161 tumors, 92 deformities/shortening, 47 pseudarthrosis, 42 fractures, 32 infected TKA, 25 osteoarthritis, 21 pyogenic arthritis, 20 infected THA, and 6 osteomyelitis. In the spinal cases, there were 136 cases of tumors, 36 cases of pyogenic spondylitis, and 35 cases of degeneration. Five modes of implant failure were identified and classified as follows: soft tissue failure (type 1), aseptic loosening (type 2), structural failure (type 3), infection (type 4), and tumor progression (type 5). Results: The overall failure rate in our series was 26.3% (172/653). There were 101 mechanical failures, including 22 type 1, 20 type 2, and 59 type 3 failures. Non-mechanical causes accounted for 71 failures, including 45 type 4 and 26 type 5 failures. The overall incidence of infections was 6.8%. The mean time to the onset of infection after implantation was 9.1 months. The overall infection rate was 3.7% in the prevention cases and 15.3% in the treatment cases. There was no difference between one-stage replacement (14.6%) and two-stage replacement (16.0%). There were 11 cases of treatment for SSI of spine surgery, and the re-infection rate was 0% using iodine-coated instruments. Conclusions: The five modes of failure of the iodine-supported implant were satisfactory compared with previous reports. In particular, because the infection rate of iodine-coated implants used for compromised hosts is low compared with other methods, postoperative infection is more easily controlled. It can be considered highly effective for spinal infections that require one-stage revision surgery. Level of evidence IV. Trial registration Prospective, Observation study. [ABSTRACT FROM AUTHOR]

A long noncoding RNA, nuclear paraspeckle assembly transcript 1 (NEAT1) variant 1 (NEAT1v1), confers radioresistance to hepatocellular carcinoma (HCC) cells by inducing autophagy via γ-aminobutyric acid A receptor-associated protein (GABARAP). Radiation induces oxidative stress to damage cellular components and organelles, but it remains unclear how NEAT1v1 protects HCC cells from radiation-induced oxidative stress via autophagy. To address this, we precisely investigated NEAT1v1-induced autophagy in irradiated HCC cell lines. X-ray irradiation significantly increased cellular and mitochondrial oxidative stress and mitochondrial DNA content in HCC cells while NEAT1v1 suppressed them. NEAT1v1 concomitantly induced the phosphatase and tensin homolog-induced kinase 1 (PINK1)/parkin-mediated mitophagy. Interestingly, parkin expression was constitutively upregulated in NEAT1v1-overexpressing HCC cells, leading to increased mitochondrial parkin levels. Superoxide dismutase 2 (SOD2) was also upregulated by NEAT1v1, and GABARAP or SOD2 knockdown in NEAT1v1-overexpressing cells increased mitochondrial oxidative stress and mitochondrial DNA content after irradiation. Moreover, it was suggested that SOD2 was involved in NEAT1v1-induced parkin expression, and that GABARAP promoted parkin degradation via mitophagy. This study highlights the unprecedented roles of NEAT1v1 in connecting radioresistance and mitophagy in HCC. [ABSTRACT FROM AUTHOR]

Surgery for bone metastasis has two primary goals—palliative care to relieve pain, instability and paralysis, and tumor resection for curing the disease. Oncologically en bloc resection, followed by a reconstruction of the bone defect is the treatment of choice in single bone metastasis from renal cell carcinoma or thyroid cancer. Bone metastases may occur in the extremities, pelvis, or spine, and different resection and reconstruction methods depend on the regional anatomy. For instance, multiple options are available for reconstruction of the pelvis, especially for the acetabulum, including anatomical reconstruction using custom-made implants or recycled autologous bone grafting when a long-term prognosis is expected. Recently, for the spine, total en bloc spondylectomy is extensively performed despite the initial limitations of surgical invasiveness, such as blood loss. Principally, palliative surgery aims to maintain lasting bony stability with minimal surgical invasiveness. Intramedullary nails and plate fixation are frequently used in the extremities but the postoperative failure rate is relatively high. Therefore, surgeons should consider the use of long intramedullary nails and long-type stems for endoprosthesis reconstruction along with cement fixation to reduce the failure rate. Although short-term complications, such as dislocation, have been observed with endoprosthesis reconstruction, it is stable in the long-term follow-up. Percutaneous bone cement injection into the spine and pelvis is also effective and less invasive. [ABSTRACT FROM AUTHOR]

Renal fibrosis compromises kidney function, and it is a risk factor for chronic kidney disease (CKD). CKD ultimately progresses to end‐stage kidney disease that can be cured only by kidney transplantation. Owing to the increasing number of CKD patients, effective treatment strategies are urgently required for renal fibrosis. TGF‐β is a well‐established fibrogenic factor that signals through SMAD2/3 signaling pathway. It was shown that there is a cross‐talk between TGF‐β/SMAD and WNT/β‐catenin signaling pathways in renal tubular epithelial cells, and that a WNT/β‐catenin inhibitor, ICG‐001, ameliorates TGF‐β1induced renal fibrosis. IC‐2, a derivative of ICG‐001, has been shown to potently induce hepatocyte differentiation of human mesenchymal stem cells by inhibiting WNT/β‐catenin signaling. In the present study, we examined the effect of ICG‐001, IC‐2, and IC‐2 derivatives (IC‐2‐506‐1, IC‐2‐506‐2, IC‐2‐506‐3, IC‐2‐Ar‐Cl, IC‐2‐OH, IC‐2‐OTBS, and IC‐2‐F) on TGF‐β1–induced SMAD activation and fibrogenic response in immortalized human renal tubular epithelial HK‐2 cells. All these compounds inhibited LiCl‐induced WNT/β‐catenin reporter activation to a similar extent, whereas ICG‐001, IC‐2‐OTBS, and IC‐2‐F almost completely suppressed TGF‐β1–induced SMAD reporter activation without apparent cytotoxicity. Phosphorylation of SMAD2/3 by TGF‐β1 was more potently inhibited by IC‐2‐OTBS and IC‐2‐F than by ICG‐001 and IC‐2. IC‐2‐F suppressed TGF‐β1–induced COL1A1 protein expression, whereas IC‐2‐506‐1 and IC‐2‐OTBS suppressed TGF‐β1–induced epithelial‐mesenchymal transition. These results demonstrated that IC‐2 derivatives suppress the TGF‐β1–induced fibrogenic response of tubular epithelial cells and thus could be promising therapeutic agents for the treatment of renal fibrosis. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Cancer stem cells (CSCs) have attracted attention as a novel therapeutic target for cancer because they play important roles in the development and aggravation of cancer. CD44 is expressed as a standard isoform (CD44s) and several variant isoforms. CD44v is a major isoform expressed on CSCs of a variety of tumors and has been extensively studied. However, HCC tissues dominantly express CD44s, whose function in CSCs remains unclear. In the present study, we investigated the roles of CD44s in CSCs of HCC. Knock‐out of the CD44 gene in HuH7 HCC cells on which only CD44s is expressed resulted in decreased spheroid formation and increased drug sensitivity. The expression of CSC marker genes, including CD133 and EpCAM, was significantly downregulated in the spheroids of CD44‐deficient cells compared with those in the spheroids of HuH7 cells. In addition, CD44 deficiency impaired antioxidant capacity, concomitant with downregulation of glutathione peroxidase 1 (GPX1) and thioredoxin. Because GPX1 uses the reduced form of glutathione (GSH) to regenerate oxidized cellular components, GSH levels were significantly increased in the CD44‐deficient cells. We also found that NOTCH3 and its target genes were downregulated in the spheroids of CD44‐deficient cells. NOTCH3 expression in HCC tissues was significantly increased compared with that in adjacent nontumor liver tissues and was correlated with CD44 expression. These results suggest that CD44s is involved in maintenance of CSCs in a HCC cell line, possibly through the NOTCH3 signaling pathway. The present study demonstrates that the standard isoform of CD44 is involved in the maintenance of cancer stem cells of a hepatocellular carcinoma cell line. We also identified NOTCH3 and glutathione peroxidase 1, thioredoxin as possible target genes of CD44 standard isoform in hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Abstract External fixation has been widely used for the treatment of limb length discrepancy, deformity correction, and bone defect using distraction osteogenesis. We have been using this technique for the treatment of obstacles due to benign bone tumor and reconstruction after malignant bone tumor resection. In this paper, we introduce the usefulness of external fixation for the treatment of various benign bone tumors and limb salvage surgery for reconstruction after tumor resection using distraction osteogenesis, according to the tumor site. The advantages of external fixation for the treatment of benign bone tumor include a possibility of complex deformity correction without treating the tumor itself and reconstruction of the aggressive benign bone tumor as well as solid fixation with wires, even for weak bone due to benign bone tumors. The advantages of treating malignant bone tumor include regeneration of living bone of sufficient strength and durability, biological affinity, resistance against infection, and lifelong restored function. The disadvantages include delayed union at the docking site and pin-or wire-tract infection, patient's psychological stress, and the procedure is time consuming. We conclude that external fixation is very efficient for the treatment of benign and malignant bone tumors. [ABSTRACT FROM AUTHOR]

Deep infection associated with implants remains a serious complication of orthopedic surgery. We developed iodine coating for titanium implants. In this study, we performed a clinical trial of iodine-coated megaprostheses to evaluate its safety and antibacterial effects. Forty-seven patients with malignant bone tumor or pyogenic arthritis were treated using iodine-supported titanium megaprostheses between July 2008 and May 2013. The mean age was 53.6 years (range, 15–85 years). Twenty-six patients were males and 21 were females. The diagnoses included malignant bone tumor in 29 cases, infected total knee arthroplasty in 11 cases, chronic osteomyelitis due to pyogenic arthritis in six cases and loosening of total knee arthroplasty in one case. The iodine-supported implants used were 42 Kyocera Limb Salvage System and five KOBELCO K-MAX K-3. These megaprostheses were used to prevent infection in 21 patients, treat active infections in 26 patients. The mean follow-up period was 30.1 months (range, 8–50). Infection was prevented in 20 out of 21 patients. Only one patient had surgical site infection caused by Pseudomonas aeruginosa and was cured by intravenous administration of antibiotics alone without removal of the implant. In 26 treatment cases involving one- or two-stage revision surgery, infection subsided without any additional surgery. In all cases, there were no signs of infection at the time of the last follow-up. White blood cell and C-reactive protein levels returned to normal within four weeks after surgery. To confirm systemic effects of iodine, thyroid hormone levels in the blood were examined. Abnormalities of thyroid gland function were not detected. Loosening of the implants was not observed. Excellent bone ingrowth and ongrowth were found around iodine-supported megaprostheses. The iodine-supported titanium megaprostheses are highly effective and show promise for the prevention and treatment of infections in large bone defects. No cytotoxicity or adverse effects were detected with this treatment. [ABSTRACT FROM AUTHOR]

Background: Low-grade osteosarcoma, including low-grade central osteosarcoma and parosteal osteosarcoma, is an extremely rare variant, and the diagnosis is occasionally difficult. In this article we present cases of low-grade osteosarcomas that should be reviewed by a clinical oncologist. Patients and methods: Nine cases of histologically diagnosed Broder grade 1 osteosarcoma were retrospectively reviewed. The pathological diagnoses included parosteal osteosarcoma, low-grade central osteosarcoma, and low-grade chondroblastic osteosarcoma in four, four, and one cases, respectively. Results: Duration from initial surgical intervention including biopsy to final diagnosis as low-grade osteosarcoma was a mean of 9.4 months. The initial benign diagnoses on biopsy specimens included fibrous dysplasia in three cases, chondroblastoma in one case, and a giant cell tumor in one case. The average number of histological examinations was 1.8. Low-grade osteosarcomas are well suited for biological reconstruction: seven cases were reconstructed by frozen autografts, distraction osteogenesis, or vascularized bone grafts. Conclusion: Low-grade osteosarcomas can be misdiagnosed as benign lesions, especially fibrous dysplasia. If the diagnosis of a low-grade osteosarcoma is not established on the basis of radiologic findings, care should be exercised, even when a biopsy suggests a benign lesion. Low-grade osteosarcomas should be treated with wide excision, even after an intralesional excision. Biological reconstruction might be a better option for low-grade osteosarcomas. [ABSTRACT FROM AUTHOR]

Highlights: [•] We investigated the relationship between expression of resistin and PAI-1. [•] PAI-1 expression was significantly decreased by resistin knockdown. [•] PAI-1 expression was rescued by addition of resistin-containing medium. [•] We conclude that resistin regulates PAI-1 expression in 3T3-L1 adipocytes. [ABSTRACT FROM AUTHOR]

Resistin, an adipose-tissue-specific secretory factor, aggravates metabolic syndrome through impairment of glucose metabolism. Previously, we demonstrated that resistin expression was induced in both 3T3-L1 cells and primary pre-adipocytes derived from Zucker obese rats during the process of differentiation and maturation (Ikeda Y, Hama S, Kajimoto K, Okuno T, Tsuchiya H & Kogure K (2011) Biol Pharm Bull 34, 865-870). However, the biological function of resistin in adipocytes is poorly understood. In the present study, we examined the effects of resistin knockdown on the biological features of 3T3-L1 cells. We found that lipid content was significantly decreased in 3T3-L1 cells transfected with anti-resistin small interfering RNA (si RNA) after adipocyte differentiation. While expression of peroxisome proliferator activated receptor γ and CCAAT/enhancer-binding protein α was not affected, protein expression and transcriptional activity levels of carbohydrate response element binding protein (Ch REBP), which upregulates transcription of lipogenic genes, decreased after anti-resistin si RNA treatment. Moreover, gene expression of fatty acid synthase and acetyl-CoA carboxylase 2, which are known to be regulated by Ch REBP, were also suppressed by resistin knockdown. In contrast, activity of the fatty acid β-oxidation-regulating protein carnitine palmitoyltransferase 1 increased. These results suggest that resistin knockdown induces suppression of lipid production and activation of fatty acid β-oxidation. Consequently, resistin may affect lipid metabolism during adipocyte maturation. [ABSTRACT FROM AUTHOR]

A long noncoding RNA (lncRNA), nuclear enriched abundant transcript 1 (NEAT1) variant 1 (NEAT1v1), is involved in the maintenance of cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). CSCs are suggested to play important roles in therapeutic resistance. Therefore, we investigated whether NEAT1v1 is involved in the sensitivity to radiation therapy in HCC. Gene knockdown was performed using short hairpin RNAs, and NEAT1v1-overexpressing HCC cell lines were generated by stable transfection with a NEAT1v1-expressing plasmid DNA. Cells were irradiated using an X-ray generator. We found that NEAT1 knockdown enhanced the radiosensitivity of HCC cell lines and concomitantly inhibited autophagy. NEAT1v1 overexpression enhanced autophagy in the irradiated cells and conferred radioresistance. Gamma-aminobutyric acid receptor-associated protein (GABARAP) expression was downregulated by NEAT1 knockdown, whereas it was upregulated in NEAT1v1-overexpressing cells. Moreover, GABARAP was required for NEAT1v1-induced autophagy and radioresistance as its knockdown significantly inhibited autophagy and sensitized the cells to radiation. Since GABARAP is a crucial protein for the autophagosome-lysosome fusion, our results suggest that NEAT1v1 confers radioresistance to HCC by promoting autophagy through GABARAP. [ABSTRACT FROM AUTHOR]

Background: Clear cell sarcoma is a rare malignant tumor of soft tissue which is most commonly encountered in the extremities, especially in the foot and ankle. This tumor is slow-growing and looks like a benign tumor; it is therefore often treated inadequately and its high rate of recurrence and metastases results in a poor prognosis. Caffeine has been used as a chemotherapy potentiator that inhibits DNA damage repair and enhances the cytocidal effects of anti-cancer drugs. This study reports the effect of caffeine-potentiated chemotherapy for clear cell sarcoma in five patients. Methods: Caffeine-potentiated chemotherapy was administered to five patients with clear cell sarcoma. Three to five courses of intra-arterial chemotherapy using cisplatin, doxorubicin and caffeine were administered preoperatively, at 3-week intervals. Conservatively, wide margin surgery was performed following the preoperative chemotherapy. Intravenous cisplatin and doxorubicin with caffeine were administered three to six times to the patients who responded to the preoperative chemotherapy. This study evaluated the response to chemotherapy, recurrence, metastasis and the overall prognosis in these five patients. Results: Four of the eligible patients responded to preoperative chemotherapy. Local recurrence occurred in only one of the five patients. Distant metastasis newly developed in one patient. All five patients survive. Conclusion: Caffeine-potentiated chemotherapy can be effective treatment for clear cell sarcoma not only as initial therapy, but also as salvage therapy. [ABSTRACT FROM AUTHOR]

The incidence of advanced hepatocellular carcinoma (HCC) is increasing worldwide, and its prognosis is extremely poor. Interferon-alpha (IFN-α)/5-fluorouracil (5-FU) therapy is reportedly effective in some HCC patients. In the present study, to improve HCC prognosis, we identified the genes that are sensitizing to these agents. The screening strategy was dependent on the concentration of ribozymes that rendered HepG2 cells resistant to 5-FU by the repeated transfection of ribozymes into the cells. After 10 cycles of transfection, which was initiated by 5,902,875 sequences of a ribozyme library, three genes including protein kinase, adenosine monophosphate (AMP)-activated, gamma 2 non-catalytic subunit (PRKAG2); transforming growth factor-beta receptor II (TGFBR2); and exostosin 1 (EXT1) were identified as 5-FU-sensitizing genes. Adenovirus-mediated transfer of TGFBR2 and EXT1 enhanced IFN-α/5-FU-induced cytotoxicity as well as 5-FU, although the overexpression of these genes in the absence of IFN-α/5-FU did not induce cell death. This effect was also observed in a tumor xenograft model. The mechanisms of TGFBR2 and EXT1 include activation of the TGF-β signal and induction of endoplasmic reticulum stress, resulting in apoptosis. In HCC patients treated with IFN-α/5-FU therapy, the PRKAG2 mRNA level in HCC tissues was positively correlated with survival period, suggesting that PRKAG2 enhances the effect of IFN-α/5-FU and serves as a prognostic marker for IFN-α/5-FU therapy. In conclusion, we identified three genes that chemosensitize the effects of 5-FU and IFN-α/5-FU on HCC cells and demonstrated that PRKAG2 mRNA can serve as a prognostic marker for IFN-α/5-FU therapy. [ABSTRACT FROM AUTHOR]

Background: Postoperative infection associated with implants remains a serious complication in orthopedic surgery. Several biomaterial surface treatments have been proposed as a means of reducing the incidence of implant-associated infections. In this study, a clinical trial was performed using an iodine-supported titanium that suppresses the microbial activities. Methods: A total of 222 patients with postoperative infection or compromised status were treated using iodine-supported titanium implants. The mean age of the patients was 49.4 years (range 5-85 years). One hundred twenty-seven patients were male and 95 were female. In 158 patients, iodine-supported implants were used to prevent infection, such as compromised hosts and conditions, and in 64 patients to treat active infection. White blood cell (WBCs) and C-reactive protein (CRP) levels were measured pre- and postoperatively in all patients. To confirm whether iodine from the implant affected physiological functions, thyroid hormone levels in the blood were examined. Both examinations were conducted sequentially for a year. Radiological evaluations were performed regularly after the operation. The chronological changes of the iodine amount were evaluated using half pins removed after completion of external fixation. Results: The mean follow-up period was 18.4 months (range 3-44 months). Acute infection developed in three tumor cases among the 158 patients on preventive therapy. All three recovered without removal of the implants. Infection was cured in all 64 patients with infection. Median WBC levels were in the normal range, and median CRP levels returned to <0.5 within 4 weeks after surgery. Abnormalities of thyroid gland function were not detected. None of the patients experienced loosening of the implants. There were two patients with mechanical implant failure, which was treated by re-implantation. Excellent bone ingrowth and ongrowth were found around all hip and tumor prostheses. One year later, the amount of iodine on external fixation pins remained about 20-30 %. Conclusions: Iodine-supported titanium implants can be very effective for preventing and treating infections after orthopedic surgery. Cytotoxicity and adverse effects were not detected. [ABSTRACT FROM AUTHOR]

Bone sarcoma often occurs in childhood, as well as in adolescents and young adults (AYAs). AYAs differ from pediatric patients in that their bone is skeletally mature and the physis has almost disappeared with the completion of growth. Although AYAs spend less time outside, they often participate in sports activities, as well as driving, working, and raising a family, which are natural activities in daily living. Multidisciplinary approaches involving imaging, multi-agent chemotherapy, surgical procedures, and careful postoperative care has facilitated an increase in limb-sparing surgery for bone sarcoma. In addition, recent advances in imaging modalities and surgical techniques enables joint-preservation surgery, preserving the adjacent epiphysis, for selected patients following the careful assessment of the tumor margins and precise tumor excision. An advantage of this type of surgery is that it retains the native function of the adjacent joint, which differs from joint-prosthesis replacement, and provides excellent limb function. Various reconstruction procedures are available for joint-preserving surgery, including allograft, vascularized fibula graft, distraction osteogenesis, and tumor-devitalized autografts. However, procedure-related complications may occur, including non-union, infection, fracture, and implant failure, and surgeons should fully understand the advantages and disadvantages of these procedures. The longevity of the normal limb function for natural activities and the curative treatment without debilitation from late toxicities should be considered as a treatment goal for AYA patients. This review discusses the concept of joint-preservation surgery, types of reconstruction procedures associated with joint-preservation surgery, and current treatment outcomes. [ABSTRACT FROM AUTHOR]

Abstract: We observed that neonates who cried during bathing on day 2 still cried on days 3 and 4. The correlation coefficient, for example, between day 2 and day 3 was r =0.410, p <0.001, n =100. Neonates may already have a distinct temperament (withdrawal and adaptability) as early as day 2 after birth. [Copyright &y& Elsevier]

The article describes the case of a 14-year-old Japanese female patient who was diagnosed with high-grade undifferentiated pleomorphic sarcoma of pelvis. The patient complained of a two-week history of pain in her right hip after falling on an icy road. Physical and radiographic tests on the patient revealed osteolytic lesion around the right acetabulum. The patient received caffeine-potentiated chemotherapy and underwent curettage and bone graft.

Imaging with fluorescent proteins has been revolutionary and has led to the new field of in vivo cell biology. Many new applications of this technology have been developed. Green fluorescent protein (GFP)-labeled or red fluorescent protein (RFP)-labeled HT-1080 human fibrosarcoma cells were used to determine clonality of metastasis by imaging of metastatic colonies after mixed implantation of the red and green fluorescent cells. Resulting pure red or pure green colonies were scored as clonal, whereas mixed yellow colonies were scored as nonclonal. Dual-color fluorescent cancer cells expressing GFP in the nucleus and RFP in the cytoplasm were engineered. The dual-color cancer cells enable real-time nuclear-cytoplasmic dynamics to be visualized in living cells in vivo, including mitosis and apoptosis. The nuclear and cytoplasmic behavior of dual-color cancer cells in real time in blood vessels was observed as they trafficked by various means or extravasated in an abdominal skin flap. Dual-color cancer cells were also visualized trafficking through lymphatic vessels where they were imaged via a skin flap. Seeding and arresting of single dual-color cancer cells in the lung, accumulation of cancer-cell emboli, cancer-cell viability, and metastatic colony formation were imaged in real time in an open-chest nude mouse model using assisted ventilation. Novel treatment was evaluated in these imageable models. UVC irradiation killed approximately 70% of the dual-color cancer cells in a nude mouse model. An RFP-expressing glioma was transplanted to the spinal cord of transgenic nude mice expressing nestin-driven green fluorescent protein (ND-GFP). In ND-GFP mice, GFP is expressed in nascent blood vessels and neural stem cells. ND-GFP cells staining positively for neuronal class III-β-tubulin or CD31 surrounded the tumor, suggesting that the tumor stimulated both neurogenesis and angiogenesis. The tumor caused paralysis and also metastasized to the brain. The Salmonella typhimurium A1-R tumor-targeting bacterial strain was administered in the orthotopic spinal cord glioma model. The treated animals had a significant increase in survival and decrease in paralysis. S. typhimurium A1-R was effective against primary bone tumor and lung metastasis expressing RFP in a nude mouse model. S. typhimurium A1-R was effective against both axillary lymph and popliteal lymph node metastases of human dual-color pancreatic cancer and fibrosarcoma cells, respectively, as well as lung metastasis of the fibrosarcoma in nude mice. Imaging with fluorescent proteins will reveal mechanisms of cancer progression and provide visual targets for novel therapeutics. [ABSTRACT FROM AUTHOR]

Background: Giant-cell tumor (GCT) of bone is a common primary benign tumor with high local recurrence and potential distant metastasis or malignant transformation. We have investigated the clinical behavior of recurrent GCT of bone in the extremities. Methods: We retrospectively reviewed 110 patients with recurrent GCTs of bone in the extremities treated by the Eastern Asian Musculoskeletal Oncology Group. The factors that affected the number of recurrences and distant metastasis were analyzed. Results: The median interval between initial surgery and the first recurrence of GCT was 16 months (2-180 months). All patients received additional surgery for first recurrence. Twenty-five patients had a second recurrence and 6 patients had a third recurrence. The mean interval between the initial surgery and the first recurrence correlated with the eventual number of recurrences-14.1 months for the repeated recurrence groups (two and three recurrences) and 28.3 months for the single recurrence group ( p = 0.016). Campanacci grade did not correlate with repeated recurrence ( p = 0. 446). The venue of the initial surgery did not correlate with recurrence but did affect preservation of the adjacent joint (chi-squared test; p = 0.046). Campanacci grade II and III also correlated with sacrifice of the adjacent joint ( p = 0.020). The incidence of lung metastasis and malignant transformation were 7.5% (8 out of 107 patients) and 2.7% (3 out of 110 patients), respectively. Repeat recurrence was associated with lung metastasis ( p = 0.018). Conclusions: Early local recurrence of GCT is a risk factor for repeat recurrence. Repeat recurrence also correlates with lung metastasis. Recurettage with meticulous adjuvant treatment to completely preclude recurrent lesions is a reasonable method for preserving the adjacent joint. However, a continuous careful follow-up is mandatory. [ABSTRACT FROM AUTHOR]

Background: Several reports suggest diffusion of anticancer agents from bone cement may suppress tumor growth. New drug delivery systems have been developed that incorporate anticancer drugs into calcium phosphate cement (CPC) to maintain high concentrations of anticancer drugs at local sites. We investigated whether CPC implants containing anticancer drugs and caffeine, which enhance the cytocidal effect of anticancer drugs, would enhance their antitumor effects on rat osteosarcomas (SOSN2 cells). Methods: We calculated the release of cisplatin (CDDP) and caffeine from the CPC and bone cement. The following CPCs were prepared: CPC-only, CPC containing caffeine, CPC containing cisplatin, and CPC containing cisplatin and caffeine. We performed cell growth inhibition assays on SOSN2 cells using culture media previously used to incubate each CPC. We transplanted SOSN2 cells into the tibias of rats, excised the tumor 3 days after transplantation, implanted each CPC and observed subsequent tumor growth. Results: The in vitro sustained-release test demonstrated greater amounts and more persistent release of CDDP and caffeine from CPC than from bone cement and also showed CPC could release the majority of its loaded CDDP and caffeine. Culture media containing CDDP and caffeine inhibited in vitro proliferation of SOSN2 cells, and this inhibitory effect was greater than the inhibition resulting from CDDP alone. Experiments with an in vivo rat model demonstrated greater tumor growth inhibition with CPC containing CDDP and caffeine than with CPC containing CDDP alone. Conclusions: The study results suggest CPC containing CDDP and caffeine potentiate antitumor effects and may be effective as a local chemotherapeutic method of treating malignant bone tumors. [ABSTRACT FROM AUTHOR]

We have recently reported that hyperdynamic state of retinoid metabolism, which may lead to the shortage of retinoid, is observed in patients with non-alcoholic fatty liver disease (NAFLD). Hepatic iron overload, which causes production of reactive oxygen species (ROS), is also frequently seen in NAFLD patients. The aim of the study is to examine iron state and retinoid metabolic state simultaneously, and to clarify the relationship between two disorders. Thirty-six persons, comprising 17 patients with simple steatosis (SS), 11 with NASH, and 8 normal controls (N), were examined on hepatic expression of iron metabolism-related genes including hemojuvelin (HJV), hepcidin (HEPC), transferrin receptor 1 and 2 (TfR1, TfR2), ferroportin (FPN), neogenin (NEO) and ferritin heavy chain (FtH) and hepatic iron contents in addition to expression 51 genes which is involved in retinoid metabolism and antioxidative action. In patients with NAFLD, expression of HJV, TfR2, FPN, TfR1, FtH, SOD and catalase was increased, compared with that in N. In addition, hepatic iron content, which was increased in NASH, was correlated with expression level of TfR2. Expression of cellular retinoid binding protein ( CRBP1), alcohol dehydrogenase 1 ( ADH1) and cytochrome P450 26A1( CYP26A1) was significantly correlated with that of HJV, TfR2 and FPN, respectively. The results of the present study suggest that the reasons responsible for iron accumulation in NASH in the present study may partly be due to enhanced expression of TfRs, especially TfR2, and hyperdynamic state of retinoid metabolism is closely related to iron metabolism in the disease. [ABSTRACT FROM AUTHOR]

Aims: Although bone marrow cells are reported to migrate to the liver under circumstances of severe liver injury, the bone marrow cell type and the mechanisms in this process, remain to be clarified. We examined the involvement of hepatocyte growth factor (HGF) in this process and the cell type of migrated hematopoietic cells by HGF. Methods: The CD34+ cells and colony forming cells in the peripheral blood were examined in HGF transgenic, recombinant HGF-administered, and HGF-expressing adenovirus-administered mice. The cell type mobilized by HGF was examined by the percentages of donor cells in the peripheral blood of the recipient mice transplanted with Lin-c-kit+Sca-1+CD34+ cells and those with Lin-c-kit+Sca-1+CD34- cells. Expression of stem cell factor (SCF) was examined after the addition of HGF in MS-5 stromal cells. The numbers of the cells which were mobilized from bone marrow and recruited into liver by HGF were assessed using green fluorescence fluorescent (GFP)-chimera mice. Results: Mobilized CD34+ cells and colony forming cells in the peripheral blood were increased by HGF treatment. The cells mobilized by HGF were mostly Lin-c-kit+Sca-1+CD34+ cells. Recruitment of bone marrow cells into liver was not suppressed in MMP-9-/- mice. Expression of SCF was induced by HGF in MS-5 stromal cells. However, expression of CXCR4, SDF-1, MMP-9 or VCAM-1 was not changed. The numbers of GFP-positive cells in liver 1 month after treatment by HGF was greater than that by G-CSF. Conclusion: The results of the present study suggest that HGF mobilizes and recruits hematopoietic progenitor cells from bone marrow into the liver through SCF-mediated mechanism. [ABSTRACT FROM AUTHOR]

Standardizing limb salvage surgery for malignant bone tumors should result in improved limb function after tumor excision and reconstruction. Recently, we developed and clinically applied a method of biological reconstruction using tumor-bearing autografts treated with liquid nitrogen. We report this newly modified technique using pedicle frozen autografts to save the continuity of anatomical structures. We treated 33 malignant bone tumor patients. Diagnoses of the tumors were 17 osteosarcomas, 11 metastatic tumors, 2 Ewing’s sarcomas, 2 chondrosarcomas, and 1 undifferentiated pleomorphic sarcoma. The sites of the tumors were 23 femurs, 5 tibias, 4 humeri, and 1 calcaneus. Operative procedures consisted of exposing the tumor, performing one-site osteotomy or joint dislocation, rotating and freezing the tumor lesion in liquid nitrogen for 20 min, and reconstruction using intramedullary nailing, plates, or composite arthroplasty. Postoperative function was excellent in 25 patients (75.7%), good in 5 patients (15.1%), and fair in 3 patients (9.0%). At the final follow-up, 8 patients had died at a mean of 17 months postoperatively, and 18 patients remained disease-free for a mean follow-up period of 30 months (range 7–69 months). Seven patients were alive but with disease. Complications were encountered in 12 patients, including 4 deep infections, 3 fractures, 3 local recurrences from surrounding soft tissue, 2 nonunions, and 1 collapse. All were managed successfully. The pedicle frozen autograft, which was newly developed to solve drawbacks of previously reported free frozen autografts, achieved success for reconstruction of malignant bone tumors. This is a new, simple, effective surgical technique for biological reconstruction that is still investigated but has potential for development. [ABSTRACT FROM AUTHOR]

Abstract: CD437, a synthetic retinoid, has a potent antitumor activity, in which an RAR-independent mechanism may be involved. Our previous study showed that CD437 transcriptionally upregulates the expression of thioredoxin-binding protein 2 (TBP2), leading to c-Jun N-terminal kinase 1 (JNK1)-mediated apoptosis. In the present study, we addressed the mechanism, by which CD437 induces TBP2 mRNA expression. CD437 efficiently caused the cell death of human osteosarcoma cells via apoptosis. CD437 also induced JNK1 activation through the upregulation of TBP2 mRNA, in consistent with our previous observation. A luciferase reporter assay for TBP2 promoter activation suggested that CD437-regulated TBP2 mRNA transcription requires the region between −400 and −300, which contains multiple possible ETS-binding sites. Finally, we demonstrated CD437-dependent recruitment of ETS1 transcription factor to this region by chromatin immunoprecipitation assay. These data suggest that ETS1 is involved in CD437-induced TBP2 mRNA expression in human osteosarcoma MG-63 cells. [Copyright &y& Elsevier]

Infections following limb-saving surgeries still happen frequently and are refractory to treatment, even though the treatment of massive bone defects caused by bone resection of bone tumors has improved gradually. Once infections become intractable, they generally result in amputations in spite of all kinds of treatment. We report the case of a patient who developed an intractable infection after limb-saving surgery utilizing a massive frozen autograft and a tumor prosthesis, but whose limb was finally successfully salvaged by multiple surgical interventions. We conclude that continued perseverance in treatment after infections may enable preservation of the limb and restoration of good function. [ABSTRACT FROM AUTHOR]

Correction of deformities about knee joint may prevent or delay the onset of osteoarthritis or mitigate its effects. Accurate correction of such deformities without production of secondary deformities depends on precise localization and quantification of the deformities. We corrected deformities around the knee using acute correction with focal dome osteotomy in 21 segments (15 patients). Five segments underwent limb lengthening postoperatively. The mean correction angle was 16.0°. We were able to correct all segments. In the five lengthening cases, the mean external fixation index (EFI) was 70.9 days/cm, which is much higher than the generally reported EFI. There were eight complications, all but one of which occurred in lengthening cases. We believe that acute correction with focal dome osteotomy is very useful for cases of alignment correction, but is not indicated for cases of alignment correction with lengthening, due to a high risk of complications related to poor callus formation. [ABSTRACT FROM AUTHOR]

We performed correction for bowing deformity of the lower extremities due to vitamin D-resistant hypophosphatemic rickets of three adults, six segments. The operative method was gradual correction and lengthening using distraction osteogenesis by Ilizarov external fixator or Heidelberg external fixator. The orders of the corrections were simultaneous correction of the bilateral femur for one patient, simultaneous correction of the ipsilateral leg for one patient, and diagonal correction of the bilateral leg for one patient. The mean correction angle was 30.5°. The mean external fixation period was 146 days. Each orders of the corrections had its merits and demerits. All patients obtained a physiological alignment and good bone formation by taking Vitamin D and oral phosphate supplements even an adult patient. All the patients had articular pain, such as hip, knee, and ankle, however, these pains healed up. All the patients were satisfied with the outcomes at the time of the final follow-up interview in terms of their cosmetic improvement. Distraction osteogenesis for bowing deformity of the lower extremities due to vitamin D-resistant hypophosphatemic rickets was very effective method and could be applied to adult patients. However, the order of the corrections should be considered carefully depending on each patient. [ABSTRACT FROM AUTHOR]

A 606-base single-stranded (ss) DNA fragment, prepared by restriction enzyme digestion of ss phagemid DNA, corrects a hygromycin resistance and enhanced green fluorescent protein (Hyg-EGFP) fusion gene more efficiently than a PCR fragment, which is the conventional type of DNA fragment used in gene correction. Here, a tailed duplex, obtained by annealing an oligonucleotide to the ss DNA fragment, was used in the correction. The tailed duplex may be a good substrate for the RAD51 protein, an important enzyme in homologous recombination, which could be the gene correction pathway. The annealing of the oligonucleotides enhanced the correction efficiency of the Hyg-EGFP gene, especially when annealed in the 3′-region of the ss DNA fragment. Both the length and backbone structure of the oligonucleotides affected the gene correction efficiency. This type of gene correction device was also effective for another target gene, the rpsL gene. The results obtained in this study indicate that tailed duplex DNA fragments are effective nucleic acids for gene correction. [ABSTRACT FROM AUTHOR]

Abstract: Retinoids play an important role in the regulation of cell growth and death. Synthetic retinoid CD437 reportedly induces apoptosis in various cancer cell lines. However, the mechanism of inducing apoptosis in hepatocellular carcinoma (HCC) cells by this agent remains to be clarified. In this study, we investigated the signaling pathway by which CD437 induces apoptosis in HCC cell lines. Apoptosis of six human HCC cell lines was induced by treatment with CD437. Caspase-3 and -9 were activated by CD437, suggesting that the apoptosis is mediated by mitochondrial pathways. Consistent with these findings, the treatment with CD437 upregulated Bax protein, downregulated Bcl-2 protein and released cytochrome c into the cytoplasm. Moreover, rhodamine123 staining revealed mitochondrial depolarization in the cells treated with CD437. These data of the present study suggest that CD437 induces apoptosis in HCC cells via mitochondrial pathways. [Copyright &y& Elsevier]

Abstract: A synthetic retinoid, CD437, has been shown to exert potent anti-tumor activity against various types of cancer cell lines, regardless of their sensitivities to natural retinoids. We herein demonstrate that CD437 induces endoplasmic reticulum (ER) stress, including the up-regulation of CHOP, BIP and GADD34 mRNA through ER stress transducer (PERK and IRE1α) activation in an ovarian adenocarcinoma cell line, SKOV3. It was also shown that CD437 induced the CHOP and GADD34 expressions in another four ovarian adenocarcinoma cell lines, indicating that CD437 functions as an ER stress inducer in these cell lines. Moreover, the siRNA-mediated knockdown of inducible CHOP expression prevented the cytotoxic effect of CD437. These results suggest that ER stress plays an important role in the mechanism by which CD437 induces apoptosis in ovarian adenocarcinoma cells. [Copyright &y& Elsevier]

Abstract: Since damage to DNA and other cellular molecules by reactive oxygen species ranks high as a major culprit in the onset and development of colorectal cancer, the aim of the present study is to clarify the role of antioxidant seleonoproteins including glutathione peroxidase (GPx), thioredoxin reductase (TXR) and selenoprotein P (SePP), and the effect of oxidative stress on the progression of colorectal cancer. Expression of 14 oxidative stress-related molecules in both tumorous and non-tumorous tissues in 41 patients was examined by immunohistochemistry and Western blot analysis. Expression levels of proteins modified by 4-hydroxy-2-nonenal (4-HNE), malonyldialdehyde (MDA) and 4-hydroxy-2-hexenal (4-HHE), and the positive rate of 8-hydroxy-2’-deoxyguanosine (8-OHdG) in tumorous tissues were much higher than those in non-tumorous tissues. Glutathione (GSH) content in tumor tissues was much lower than that in non-tumorous tissues. Expression level of selenoproteins such as GPx-1, GPx-3, and SePP, which are rapidly degraded during selenium deprivation, was significantly decreased in tumorous tissues, whereas that of GPx-2, which is resistant to selenium deprivation, was increased. Expression of SePP was decreased at stage III and IV, compared to that of stage II. These data suggest that contrasting expression pattern of the antioxidant selenoproteins plays an important role in the progression of colorectal cancer. [Copyright &y& Elsevier]

Abstract: The mechanisms of prevention of the development of liver cancer by NIK-333, an acyclic retinoid (ACR), were investigated. The transgenic mice expressing the dominant negative form of retinoic acid receptor α (RARE mice), that produce reactive oxygen species and lead to development of liver tumor were used. The effect of NIK-333 on hepatocarcinogenesis in RARE mice was studied. The RARE mice were examined after feeding 0.03% and 0.06% NIK-333 diets at 12 months of age. In the mice fed 0.06% NIK-333 diet, tumor incidence was greatly suppressed, compared to that of wild type mice (0/9 versus 5/9, P <0.05), but not in the mice fed 0.03% NIK-333 diet. In addition, expression of cytochrome p450 4a14 and acyl-CoA oxidase was normalized, and the percentages of positive cells for 8-hydroxy-2′-deoxyguanosine, 4-hydroxy-2-nonenal and proliferating cell nuclear antigen were decreased. Furthermore, expression of β-catenin and cyclin D1 was also depressed. These data suggest that NIK-333 suppressed liver tumor in association with repression of oxidative stress. [Copyright &y& Elsevier]

Abstract: Retinoids have several biological functions including cell growth, differentiation and apoptosis. In liver, retinoids are known to be associated with regeneration, fibrosis and carcinogenesis. The facts that retinoid droplets in stellate cells are lost with progression of liver disease and that effectiveness of an acyclic retinoid on second primary liver cancer suggest the importance of liver as a target organ of retinoids. Our recent work has indicated that retinoids have antioxidant effects in association with regulation of fatty acid metabolism. In this review article, we discussed the important function of retinoids in liver, mainly from molecular aspects. [Copyright &y& Elsevier]

Background: Hearing loss is one of the most common abnormalities present at birth. The authors examined the frequency of newborn hearing disturbance at a single obstetric hospital to exclude technical varieties or varieties of subjects which are inevitable in multiple institutional cooperative studies. Methods: The newborns were examined with an automated auditory brainstem response screener, the ALGO 2e, on day 4 post-partum. This Screener uses 35 dB near hearing level click stimuli and provides a PASS/REFER result that requires no interpretation. The PASS result is accepted as adequate evidence of hearing and REFER result as required further diagnostic testing to determine hearing status. Screenings of REFER outcomes were repeated at 1 month of age. Comparisons were made of the results and the Japanese multiple institutional trials by Mann–Whitney U-test. Results: The authors screened 8979 out of 13 494 neonates born from July 1999 to October 2004. The neonates with unilateral or bilateral REFER outcomes were 37 cases (0.41% of the total examined) on day 4, and 31 cases (0.35%) at 1 month of age. Five of the 31 neonates had PASS outcomes at 6 months of age. Among the 31 REFER neonates, eight (25.8%) had otolaryngeal complications. Conclusion: In the present study, screening results at 1 month of age resembled the final diagnosis obtained at 6 months of age; out of 31 REFER cases, 26 cases were diagnosed with hearing loss. In contrast, in the multiple institutional study, both unilateral and bilateral REFER rates were much higher than the rates of final hearing loss. Concerning the final diagnoses of bilateral hearing loss, the authors’ results (0.10%) and the multiple institutional studies’ results (0.05% in low-risk and 2.19% in high-risk neonates) were comparable to the results reported in the USA. To expand the newborn hearing screening program, it is crucial that authority and institutions concerned promote the development of a national or prefecture-based early hearing loss identification and intervention network. [ABSTRACT FROM AUTHOR]

We describe a 47-year-old man with a giant cell tumor of bone involving the acetabulum treated with curettage and bone grafting which resulted in good remodeling of the hip joint. The patient had a 15 × 18-cm2 mass lesion extending from the right ischium to the acetabulum. Treatment included curettage, phenol, and ethanol application as an adjuvant, and cancellous bone allografting was performed on the subchondral area of the acetabulum. The posterior column of the acetabulum was disappeared by tumor invasion. Despite central migration of the femoral head, adequate hip joint repair was achieved without surgery 5.5 years postoperatively and with no tumor recurrence. The patient could walk without pain or ambulation aids; hip range of motion was 100° for flexion, 0° for extension, 30° for abduction, 45° for external rotation, and 10° for internal rotation, and the functional result was 93.3% in the Enneking scoring system. We performed intralesional curettage with phenol and ethanol adjuvant therapy for pelvic giant cell tumor without tumor recurrence, and good repair of a hip joint adaptation can be achieved even in an adult patient. [ABSTRACT FROM AUTHOR]

Abstract: A 606-nt single-stranded (ss) DNA fragment, prepared by restriction enzyme digestion of ss phagemid DNA, improves the gene correction efficiency by 12-fold as compared with a PCR fragment, which is the conventional type of fragment used in the small fragment homologous replacement method [H. Tsuchiya, H. Harashima, H. Kamiya, Increased SFHR gene correction efficiency with sense single-stranded DNA, J. Gene Med. 7 (2005) 486–493]. To reveal the characteristic features of this gene correction with the ss DNA fragment, the effects on the gene correction in CHO-K1 cells of the chain length, 5′-phosphate, adenine methylation, and transcription were studied. Moreover, the possibility that the ss DNA fragment is integrated into the target DNA was examined with a radioactively labeled ss DNA fragment. The presence of methylated adenine, but not the 5′-phosphate, enhanced the gene correction efficiency, and the optimal length of the ss DNA fragment (∼600 nt) was determined. Transcription of the target gene did not affect the gene correction efficiency. In addition, the target DNA recovered from the transfected CHO-K1 cells was radioactive. The results obtained in this study indicate that length and adenine methylation were important factors affecting the gene correction efficiency, and that the ss DNA fragment was integrated into the double-stranded target DNA. [Copyright &y& Elsevier]

We tested the efficacy of 4 local agents for protection against tumor growth after tumor contamination and tumor bloc inoculation. Tumors were prepared by injecting human HT-1080 fibrosarcoma cells into the subcutaneous tissue of 6–9 week old male athymic nude mice (BALB/c nu/nu). When the tumors reached the desired size, the nude mice were sacrificed, and the tumors were harvested en bloc. Then the tumors were used in either contamination group or tumor inoculation group. In the contamination group, 34 tumors were cut by Gigli saw (Group G) and 35 tumors were cut by No. 11 scalpel (Group S). The cut surface of the tumor was rubbed into the subcutaneous tissues of non-tumor bearing nude mice for 10 seconds. Then, the nude mice from the S and G groups were randomized into either one of five subgroups: groups S–N and G–N: no local agent was used, groups S–S and G–S: lavage by saline, groups S–P and G–P: lavage by povidone iodine 10%, groups S–H and G–H: lavage by hydrogen peroxide 3%, groups S–C and G–C: lavage by cisplatin and distilled water. In the tumor inoculation group, a tumor weight of 100 mg was inoculated into 32 non-tumor bearing nude mice. Then, the nude mice were randomized into either of 5 subgroups: group B–N: no local agent was used, group B–S: lavage by saline, group B–P: lavage by povidone iodine 10%, group B–H: lavage by hydrogen peroxide, group B–C: lavage by cisplatin and distilled water. For lavage, the fluid was kept in the wound for 5 minutes apart from the cisplatin which was kept in the wound for 2.5 minutes and then the wound was filled with distilled water for the next 2.5 minutes. Tumor growth occurred in S–N, S–S, S–H, S–P and S–C groups in 33.3%, 67.7%, 16.7%, 16.7%, and 0% respectively. Tumor growth occurred in G–N, G–S, G–H, G–P, and G–C groups in 50%, 67.7%, 33.3%, 33.3%, and 0%, respectively. The total growth incidence after tumor contamination in the no-agent, saline, hydrogen peroxide, povidone iodine and cisplatin groups were 41.7%, 58.3%, 25%, 25% and 0%, respectively. Growth occurred in 100% of B–N and B–S groups, 83% of B–H and B–P groups and 33.3% of the B–C group. Cisplatin used for 2.5 minutes followed by distilled water for 2.5 minutes is effective for protection against local tumor recurrence due to tumor contamination. It also has a reasonable effect against tumor blocks. [ABSTRACT FROM AUTHOR]

Abstract: Unmethylated CpG dinucleotides in DNA contribute to a rapid inflammatory response in mammals. Here we show that N6-methyladenine (N6-MeA), a bacterium-specific modified base, also causes cytokine production. An oligodeoxyribonucleotide (ODN) containing N6-MeA induced cytokines when injected into mice. Co-injection of N6-MeA and CpG ODNs enhanced cytokines 2- to 3-fold, as compared with the injection of a CpG ODN alone. Plasmid DNA containing N6-MeA, complexed with cationic lipids, induced IL-12. These results indicate that the bacterium-specific base, in addition to the unmethylated CpG motif, triggers the mammalian immune response, and suggest that N6-MeA-containing DNA could be useful for cellular immunotherapy and DNA vaccine. [Copyright &y& Elsevier]

We investigated the effects of low-intensity pulsed ultrasound (LIPUS; 30 mW/cm2 spatial and temporal average) on the timing of LIPUS treatment in distraction osteogenesis. Lengthening of the right tibia was performed in 75 male Japanese white rabbits using unilateral fixators (waiting period, 7 days; distraction rate, 1.5 mm/day; distraction period, 7 days). Rabbits were divided into four groups according to the timing of the LIPUS treatment. Control group had no stimulation. Waiting group was treated with a daily 20-min session of LIPUS during a 7-day latency period. Lengthening group was treated during the lengthening period. Maturation group was treated for the first 7 days after completion of distraction. We evaluated the distraction site by radiography and histology every week for 4 weeks. Bone mineral density (BMD) and mechanical strength were tested and microfocus X-ray computed tomography was performed on specimens 2 weeks after completion of distraction. The lengthening group had greater BMD and mechanical strength than the other groups, bone regeneration was enhanced more in the maturation group than in the control or waiting groups. Histologically, endochondral bone formation in the lengthening and the maturation groups occurred earlier than in the control or waiting groups. These results suggest the LIPUS effect is mediated via endochondral pathways. We concluded that LIPUS stimulates bone formation in distraction osteogenesis and is most effective during the lengthening phase. [Copyright &y& Elsevier]

Spondylectomy for extripation of spinal tumors would be performed through piecemeal excision or by totalen bloc spondylectomy with cutting at the neural arch by the threadwire saw (T-saw) that is sometimes inevitably intralesional. The purpose of this study was to compare the potential for tumor growth after rubbing of the cut surface of tumors cut by either T-saw or blunt instrument against the subcutaneous tissues of nude mice. Tumors were prepared by subcutaneous injection of human HT 1080 fibrosarcoma cells in nude mice. The animals were sacrificed, and tumors were harvesteden bloc and cut with either a T-saw or artery forceps. A 3-cm wound was created on the backs of other (plain) nude mice. The tumor's cut surface was rubbed for 10 seconds against the subcutaneous tissue of one of these nude mice. The wounds were then sutured. Tumor blocks were inoculated into other nude mice. Nude mice were followed for occurrence of tumor growth. Tumor growth occurred in all nude mice after block inoculation. The incidence of tumor growth after rubbing with the tumor surfaces cut with T-saw and artery forceps were 16.7% and 58.3% respectively (P = 0.035). Onset of tumor growth after tumor rubbing and inoculation of tumor blocks were 30.1 ± 25 and 12.2 ± 5 days respectively (P = (0.015). Rubbing of T-saw-cut tumor surface)has less possibility of causing tumor growth than rubbing of surface of bluntly-cut tumors. [ABSTRACT FROM AUTHOR]

Background: Soft-tissue metastasis of carcinoma is rare. In the present study, we investigated the surgical indications and clinical features of patients with soft tissue metastases of carcinoma. Methods: In this retrospective cohort study, we enrolled 26 patients with soft tissue carcinoma metastasis referred to our department for treatment. Sex, age, location, size, depth, pain due to the tumor, primary origin, serum C-reactive protein (CRP) level, MRI examinations, diagnosis by a previous physician, carcinoma markers from blood, history of carcinoma, other metastases, performance status (PS), and surgical procedures were documented. Associations between variables and surgery were statistically analyzed. Results: The primary cancer origin was found to be the lung (n = 10), kidney (n = 7), esophagus (n = 2), stomach (n = 1), breast (n = 1), liver (n = 1), ureter (n = 1), anus (n = 1), and unknown (n = 2). The mean CRP level of all patients was 2.3 mg/dL. Seven tumors (26.9%) were originally suspected to be soft tissue metastases of carcinoma, while 19 tumors (73.1%) were considered soft tissue sarcomas or inflammatory lesions by the previous treating physician. Twenty patients (76.9%) had other metastases. The PS of the 12 patients (46.2%) was zero. Eleven patients (42.3%) underwent surgery for soft tissue metastases. Diagnosis of soft tissue metastasis by a previous physician and good PS (p < 0.05) were significantly associated with surgery. Conclusion: Overall, the present results show that surgical indications for soft tissue metastasis of carcinoma include diagnosis by the referring physician or good PS of the patients. [ABSTRACT FROM AUTHOR]

The current guidelines for the treatment of non-small cell lung cancer encourage local curative treatment for selected patients with oligometastases. This study evaluated the surgical results of total en bloc spondylectomy (TES) for isolated spinal metastases originating from lung cancer in carefully selected patients. We retrospectively reviewed 14 patients (7 men and 7 women) who underwent TES for spinal metastases originating from lung cancer between 2000 and 2017. The primary outcome measure was the postoperative overall survival time. The histological types included adenocarcinoma (n = 12), pleomorphic carcinoma (n = 1), and small cell lung carcinoma (SCLC) (n = 1 patient). We assessed postoperative survival using Kaplan–Meier analysis and the log-rank test. The median postoperative survival time was 83.0 months (6–162 months) in 13 patients with non-small cell lung carcinoma (NSCLC) and 6 months in 1 patient with SCLC. The 3-, 5-, and 10-year overall survival rates in patients with NSCLC were 61.5%, 53.8%, and 15.4%, respectively. Poor postoperative performance status (PS) and Frankel grade, and preoperative irradiation to the vertebrae to be resected were significantly associated with short-term survival after TES in patients with NSCLC (p < 0.05). The surgical results of TES for spinal metastases of lung cancer were relatively favorable among carefully selected patients. TES may be indicated for spinal metastases of lung cancer in patients with controlled primary lung cancer, NSCLC histology, prospect of good postoperative PS, and preferably no irradiation to the target vertebrae. [ABSTRACT FROM AUTHOR]

Although there are limited treatment options for sarcoma patients, recent studies have demonstrated promising therapeutic targets, anticancer agents, and combinations of these treatments. Although the incidence of sarcomas accounts for less than 1% of all malignancies, they are classified into more than 50 different subtypes with different biological behaviours. Chondrosarcoma, the second most common primary bone sarcoma, is characterised by the production of cartilaginous matrix and accounts for approximately 30% of malignant bone tumours. [Extracted from the article]

CD44, a cancer stem cell (CSC) marker, is required for maintaining CSC properties in hepatocellular carcinoma (HCC). Nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), is an oncogenic driver in HCC. In the present study, we investigated the significance of the NEAT1 gene in association with CD44 expression in liver CSCs of human HCC cell lines. The CSC properties were evaluated by spheroid culture, CSC marker expression, and sensitivity to anti-cancer drugs. The expression of both NEAT1 variant 1 (NEAT1v1) and variant 2 (NEAT1v2) as well as CD44 was significantly increased in the spheroid culture, compared with that in monolayer culture. Overexpression of Neat1v1, but not Neat1v2, enhanced the CSC properties, while knockout of the NEAT1 gene suppressed them. CD44 expression was increased by the overexpression of Neat1v1 and abrogated by NEAT1 knockout. The overexpression of NEAT1v1 restored the CSC properties and CD44 expression in NEAT1-knockout cells. NEAT1v1 expression in HCC tissues was correlated with poor prognosis and CD44 expression. These results suggest that NEAT1v1 is required for CD44 expression. To our surprise, NEAT1v1 also restored the CSC properties even in CD44-deficient cells, suggesting that NEAT1v1 maintains the properties of CSCs in a CD44-independent manner. [ABSTRACT FROM AUTHOR]

Unconventional prefoldin RNA polymerase II subunit 5 interactor (URI1) has emerged as an oncogenic driver in hepatocellular carcinoma (HCC). Although the hepatitis B virus (HBV) represents the most common etiology of HCC worldwide, it is unknown whether URI1 plays a role in HBV-related HCC (HCC-B). In the present study, we investigated URI1 expression and its underlying mechanism in HCC-B tissues and cell lines. URI1 gene-promoter activity was determined by a luciferase assay. Human HCC-B samples were used for a chromatin immunoprecipitation assay. We found that c-MYC induced URI1 expression and activated the URI1 promoter through the E-box in the promoter region while the HBx protein significantly enhanced it. The positivity of URI1 expression was significantly higher in HCC-B tumor tissues than in non-HBV-related HCC tumor tissues, suggesting that a specific mechanism underlies URI1 expression in HCC-B. In tumor tissues from HCC-B patients, a significantly higher level of c-MYC was recruited to the E-box than in non-tumor tissues. These results suggest that HBx and c-MYC are involved in URI1 expression in HCC-B. URI1 expression may play important roles in the development and progression of HCC-B because HBx and c-MYC are well-known oncogenic factors in the virus and host, respectively. [ABSTRACT FROM AUTHOR]

Background: Recently, the T2 alpha nailing system (Stryker, Inc.), which has advanced locking screws that can attach a screw to a rod, has been used worldwide and is expected to improve fracture fixation. We analyzed two cases of supracondylar femoral fractures in older adult patients, in which intraoperative fractures occurred during the insertion of advanced locking screws of the T2 alpha femur retrograde intramedullary nail. Case presentation: A 93-year-old and an 82-year-old woman each underwent T2 alpha femur retrograde nail fixation for supracondylar femur fractures at separate hospitals, and advanced locking screws were used as the proximal transverse locking screws. In both patients, a fracture line was observed at the proximal screw postoperatively, and the fractures were refixed with distal cable wiring and/or femoral distal plates. The patients were subsequently discharged from the same facility with no remarkable pain. Conclusions: When inserting advanced locking screws, it is necessary to enlarge the screw hole in the near-bone cortex with a counterbore drill, which might add torque to the bone cortex that could result in fractures. If the sleeve is distant from the bone, the counterbore drill will not reach the bone, the screw hole will not expand, and the insertion of advanced locking screws will apply a strong torque to the bone cortex and may result in fracture. Moreover, it is important to confirm that the counterbore drill is securely inserted under fluoroscopy and to carefully enlarge the bony foramen manually to prevent fractures during screw insertion. [ABSTRACT FROM AUTHOR]

Background: In patients with conjoined nerve roots, hemilaminectomy with sufficient exposure of the intervertebral foramen or lateral recess is required to prevent destabilization and ensure correct mobility of the lumbosacral spine. To the best of our knowledge, no case reports have detailed the long-term course of conjoined nerve roots after surgery. Case presentation: We report the case of a 51-year-old Japanese man with a conjoined nerve root. The main symptoms were acute low back pain, radiating pain, and right leg muscle weakness. Partial laminectomy was performed with adequate exposure to the conjoined nerve root. The symptoms completely resolved immediately after surgery. However, the same symptoms recurred 7 years postoperatively. The nerve root was compressed because of foraminal stenosis resulting from L5–S disc degeneration. L5–S transforaminal lumbar interbody fusion was performed on the contralateral side because of an immobile conjoined nerve root. At 44 months after the second surgery, the patient had no low back pain or radiating pain, and the muscle weakness in the right leg had improved. Conclusions: This is the first report of the long-term course of conjoined nerve root after partial laminectomy. When foraminal stenosis occurs after partial laminectomy, transforaminal lumbar interbody fusion from the contralateral side may be required because of an immobile conjoined nerve root. [ABSTRACT FROM AUTHOR]