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Find video protocols related to scientific articles indexed in Pubmed.
Outcomes and complications of reconstruction using tumor-bearing frozen autografts in patients with metastatic bone tumors.
Anticancer Res.
PUBLISHED: 10-03-2014
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Tumor-bearing frozen autografts have been used for reconstruction of bone defects after resection of bone tumors. In the present study, outcomes and complications of reconstruction using frozen autografts were assessed to determine indications for this procedure in patients with metastatic bone lesions.
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Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice.
Oncotarget
PUBLISHED: 09-13-2014
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Bone metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high bone-metastatic variant of breast cancer, all untreated mice had bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely prevented the appearance of bone metastasis of the high metastatic variant in nude mice (P < 0.001). After injection of the highly bone-metastatic breast cancer variant to the tibia of nude mice, S. typhimurium A1-R treatment significantly reduced tumor growth in the bone (P < 0.001). These data indicated that S. typhimurium A1-R is useful to prevent and inhibit breast cancer bone metastasis and should be of future clinical use for breast cancer in the adjuvant setting.
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Fluorescence-guided surgery improves outcome in an orthotopic osteosarcoma nude-mouse model.
J. Orthop. Res.
PUBLISHED: 08-19-2014
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In order to develop a model for fluorescence-guided surgery (FGS), 143B human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the intramedullary cavity of the tibia in nude mice. The fluorescent areas of residual tumors after bright-light surgery (BLS) and FGS were 10.2?±?2.4?mm(2) and 0.1?±?0.1?mm(2) , respectively (p?
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Conservative treatment for patients with osteoid osteoma: a case series.
Anticancer Res.
PUBLISHED: 07-02-2014
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Osteoid osteoma is one type of benign bone tumor that may respond to conservative treatment.
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Impact of a single nucleotide polymorphism upstream of the IL28B gene in patients positive for anti-HCV antibody in an HCV hyperendemic area in Japan.
J. Med. Virol.
PUBLISHED: 07-01-2014
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The influence of genetic variation at the interleukin-28B (IL28B) locus on the natural course of hepatitis C virus (HCV) infection has not been fully investigated. The goal of this study was to examine whether an IL28B polymorphism (rs8099917) is associated with natural clearance of HCV and with disease parameters of HCV infection in an HCV hyperendemic area of Japan. The patients were 502 anti-HCV antibody-positive residents who participated in liver disease screening program from 2002 to 2004. Patients who underwent interferon-based therapy or had hepatocellular carcinoma were excluded. Of these patients, 149 were negative for HCV RNA (prior infection) and 353 were positive for HCV RNA or HCV core antigen (HCV carriers). In multivariate analysis, the IL28B TT genotype was a predictor for prior HCV infection. In addition, nine of the patients with prior HCV infection were positive for anti-HCV antibody with positive for HCV core antigen or HCV RNA before 2001, and these nine patients all had the IL28B TT genotype. Furthermore, the IL28B TT genotype was associated independently with higher HCV core antigen levels in HCV carriers. In contrast, the IL28B genotype did not affect the biochemical markers, such as alanine aminotransferase, hepatic fibrosis markers, and ?-fetoprotein, and the degree of hepatic fibrosis assessed by transient elastography in HCV carriers. We concluded that IL28B polymorphism (TT genotype) is associated with spontaneous clearance of HCV and conversely with high viral loads in HCV carriers. In contrast, the IL28B genotype does not affect disease progression such as hepatic fibrosis.
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Synovial sarcoma in knee joint, mimicking low-grade sarcoma confirmed by molecular detection of SYT gene split.
Anticancer Res.
PUBLISHED: 06-13-2014
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A 10-year-old boy underwent arthroscopic curettage for an intra-articular mass in knee joint. The tumor was diagnosed as low-grade fibrous sarcoma. Five years later, the patient presented with a recurrent tumor. The patient underwent a marginal excision with knee joint preservation and without adjuvant therapy. Two years after the last surgery, the patient is thriving with no evidence of recurrent or metastatic disease. The final diagnosis was synovial sarcoma confirmed via a SYT gene split performed with fluorescent in situ hybridization (FISH), although the tumor appeared as a low-grade fibrous type in a hematoxylin-eosin section. The first curetted specimen was also confirmed to bear a SYT gene split. Synovial sarcoma has been conventionally recognized as a high-grade sarcoma. Our patient had a tumor that exhibited the characteristics of both a histologically and clinically low-grade tumor. From the present case, we consider that low-grade variants of synovial sarcoma do exist although their existence remains controversial.
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Fluorescence-guided surgery of prostate cancer bone metastasis.
J. Surg. Res.
PUBLISHED: 02-12-2014
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The aim of this study is to investigate the effectiveness of fluorescence-guided surgery (FGS) of prostate cancer experimental skeletal metastasis.
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Factors that influence functional outcome after total or subtotal scapulectomy: Japanese Musculoskeletal Oncology Group (JMOG) study.
PLoS ONE
PUBLISHED: 01-01-2014
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Scapulectomy requires not only joint resection but also wide resection of the shoulder girdle muscles. Even the significance of reconstruction has not yet been determined because of the difficulties in comparing the different conditions. The purpose of this study was to investigate factors that influence functional outcomes after scapulectomy in a multicenter study.
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A novel method to apply osteogenic potential of adipose derived stem cells in orthopaedic surgery.
PLoS ONE
PUBLISHED: 01-01-2014
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A number of publications have reported that adipose derived stem cells (ADSCs) have the capacity to be induced to differentiate into osteoblasts both in vitro and in vivo. However, it has been difficult to use separate ADSCs for cortical bone regeneration and bone reconstruction so far. Inspired by the research around stromal stem cells and cell sheets, we developed a new method to fabricate ADSCs sheets to accelerate and enhance the bone regeneration and bone reconstruction.
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Anatomical basis of distally based anterolateral thigh flap.
J Plast Surg Hand Surg
PUBLISHED: 11-21-2013
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Abstract Soft tissue coverage around the knee has persisted as a challenge for plastic and reconstructive surgeons. The distally-based anterolateral thigh flap is often used for coverage. Nevertheless, few anatomical studies have investigated the retrograde vascular pedicle. This report clarifies the anatomy of the connection between the descending branch of the lateral circumflex femoral artery and the lateral superior genicular artery. This study examined 38 lower limbs from cadavers and recorded the numbers and locations of perforating vessels. Proximal and distal pivot points were also recorded. The proximal pivot point was 1.0-12.1 cm (average = 6.0 cm) from the inguinal ligament. The distal pivot point, found under the vastus lateralis muscle in all 38 specimens, was 4.0-13.6 cm (average = 9.8 cm) from the lateral superior edge of the patella. The most distal perforator was 8.2-28.0 cm (average = 18.9 cm) from the proximal pivot point. The most proximal perforator was 3.0-19.5 cm (average = 8.7 cm) from the distal pivot point. Details of the anastomosis of the descending branch and the superior lateral genicular artery were clarified. The distally-based anterolateral thigh flap presents one option for reconstruction around the knee.
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Development of a new evaluation method for gelatin film sheets.
Int J Pharm
PUBLISHED: 08-05-2013
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Gelatin film sheets are often used to form the shell in soft capsules prepared using the rotary die method. Examination of the film sheet properties is extremely important when materials other than gelatin are used. We examined the relationship between the width and the tensile strength of the gelatin film sheet in order to establish the required indexes of the gelatin film sheets. The coefficients of correlation (R) of the linear regressions 4 and 15min after preparation of the gelatin film sheets were 0.9858 and 0.9167, respectively. These results suggest that the tensile strength decreased when the width of the gelatin film sheet increased. Subsequently, we examined the relationship between time and the tensile strength. We observed new phenomenon: the tensile strength of the gelatin sheets increased with time, following two phases. The first phase corresponded to over phase transition point at 4, 8, and 15min and the second phase corresponded to under transition point at 15, 30, and 60min. The R values were 0.9952 (4, 8, 15min) and 0.9494 (15, 30, 60min).
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Diagnosis and treatment of low-grade osteosarcoma: experience with nine cases.
Int. J. Clin. Oncol.
PUBLISHED: 06-26-2013
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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.
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Imaging UVC-induced DNA damage response in models of minimal cancer.
J. Cell. Biochem.
PUBLISHED: 05-09-2013
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We have previously demonstrated that the ultraviolet (UV) light is effective against a variety of cancer cells in vivo as well as in vitro. In the present report, we imaged the DNA damage repair response of minimal cancer after UVC irradiation. DNA-damage repair response to UV irradiation was imaged on tumors growing in 3D culture and in superficial tumors grown in vivo. UV-induced DNA damage repair was imaged with GFP fused to the DNA damage response (DDR)-related chromatin-binding protein 53BP1 in MiaPaCa-2 human pancreatic cancer cells. Three-dimensional Gelfoam® histocultures and confocal imaging enabled 53BP1-GFP nuclear foci to be observed within 1?h after UVC irradiation, indicating the onset of DNA damage repair response. A clonogenic assay showed that UVC inhibited MiaPaCa-2 cell proliferation in a dose-dependent manner, while UVA and UVB showed little effect on cell proliferation. Induction of UV-induced 53BP1-GFP focus formation was limited up to a depth of 40?µm in 3D-culture of MiaPaCa-2 cells. The MiaPaCa-2 cells irradiated by UVC light in a skin-flap mouse model had a significant decrease of tumor growth compared to untreated controls. Our results also demonstrate that 53BP1-GFP is an imageable marker of UV-induced DNA damage repair response of minimal cancer and that UVC is a useful tool for the treatment of residual cancer since UVC can kill superficial cancer cells without damage to deep tissue.
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Single cell time-lapse imaging of focus formation by the DNA damage-response protein 53BP1 after UVC irradiation of human pancreatic cancer cells.
Anticancer Res.
PUBLISHED: 04-09-2013
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We have previously demonstrated that ultraviolet (UV) light treatment is effective against various types of cancer cells expressing fluorescent proteins. In order to further understand the efficacy of UV treatment of cancer cells, we determined the kinetics of focus formation by imaging of a DNA damage-response (DDR) protein after UVC irradiation of human pancreatic cancer cells. A fusion protein consisting of the DDR protein 53BP1 and green fluorescent protein (GFP) (GFP-53BP1) was used as a live-cell imaging marker for cellular response after UVC irradiation. GFP-53BP1 foci were observed after UVC irradiation of MiaPaCa-2 human pancreatic cancer cells. During live-cell imaging, GFP-53BP1 foci were observed in the cells within 15 min after UVC irradiation, and some of the foci remained stable for at least three hours. GFP-53BP1 focus formation was observed in the pancreatic-cancer cells irradiated by 25-200 J/m(2) UVC. Our results indicate that an early response to DNA damage caused by UVC irradiation can be visualized by increased GFP-53BP1 focus formation by pancreatic cancer cells.
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Dynamic color-coded fluorescence imaging of the cell-cycle phase, mitosis, and apoptosis demonstrates how caffeine modulates cisplatinum efficacy.
J. Cell. Biochem.
PUBLISHED: 03-21-2013
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Caffeine enhances the effect of certain anticancer drugs, but the mechanism of modulation is poorly understood. In this study, modulation of cisplatinum efficacy induced by caffeine was visualized at the subcellular level by real-time fluorescent-protein imaging. Mitotic and apoptotic changes were observed by imaging 143B human osteosarcoma dual-color cells, in which GFP is expressed in the nucleus and RFP is expressed in the cytoplasm. Modulation of the cell cycle was imaged using time-lapse imaging of HeLa cells expressing a fluorescent ubiquitination-based cell cycle indicator (FUCCI) in the nucleus. Clonogenic assays showed that caffeine increased the inhibition by cisplatinum on cell proliferation. Subcellular imaging demonstrated that cisplatinum decreased mitosis and induced apoptosis in 143B cells. The combination of cisplatinum and caffeine enhanced mitosis and subsequently increased apoptosis. Time-lapse imaging showed that cisplatinum strongly induced cell-cycle arrest in the S/G2 phase in HeLa-FUCCI cells. Caffeine overcame the cell-cycle arrest induced by cisplatinum, thereby increasing its efficacy, since cisplatinum is ineffective against quiescent cells. The data in this report indicate that caffeine modulates the cell cycle in cancer cells, thereby enhancing efficacy of cell-cycle-dependent anticancer drugs such as cisplatinum.
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Pedicle versus free frozen autograft for reconstruction in malignant bone and soft tissue tumors of the lower extremities.
J Orthop Sci
PUBLISHED: 03-06-2013
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Of the biological reconstruction methods for malignant bone and soft tissue tumors, reconstruction with liquid nitrogen has the advantage of maintaining continuity on the distal side of the tumor bone site (pedicle freezing procedure; PFP). This method is expected to result in early blood flow recovery, with early union and low complication rate. The purpose of this study was to compare the outcomes of the PFP and free freezing procedure (FFP) in the lower extremities.
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Impact of antibody to hepatitis B core antigen on the clinical course of hepatitis C virus carriers in a hyperendemic area in Japan: A community-based cohort study.
Hepatol. Res.
PUBLISHED: 01-14-2013
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AIM: Subjects positive for antibody to hepatitis B core antigen (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are considered to have occult hepatitis B virus (HBV) infection. The aim of this study was to determine the impact of occult HBV infection on aggravation of the clinical course in hepatitis C virus (HCV) carriers. METHODS: A prospective cohort study was performed in 400 subjects who were positive for anti-HCV antibody and negative for HBsAg. Among these subjects, 263 were HCV core antigen positive or HCV RNA positive (HCV carriers). We examined whether the presence of HBcAb affected the clinical course in these HCV carriers from 1996-2005. RESULTS: The HBcAb positive rates were 53.6% and 52.6% in HCV carriers and HCV RNA negative subjects, respectively. There were no differences in the incidence of hepatocellular carcinoma (HCC) and cumulative mortality associated with liver-related death between HCV carriers who were positive and negative for HBcAb. In multivariate analysis, age (?65 years) and alanine aminotransferase level (?31?IU/L) emerged as independent risk factors for HCC development and liver-related death, but the HBcAb status was not a risk factor. In addition, increased serum hepatic fibrosis markers (measured from 2001-2004) were not associated with HBcAb status. CONCLUSION: In our cohort study, the presence of HBcAb had no impact on HCC development, liver-related death and hepatic fibrosis markers in HCV carriers. Thus, our results indicate that occult HBV infection has no impact on the clinical course in HCV carriers.
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Prognostic value of histological response to chemotherapy in osteosarcoma patients receiving tumor-bearing frozen autograft.
PLoS ONE
PUBLISHED: 01-01-2013
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A variety of surgical procedures are now available for tissue reconstruction after osteosarcoma excision, and an important prognostic factor is the evaluation of response to chemotherapy using histology. Although tumor-bearing autografts are useful tools for reconstruction, re-use of the primary tumor may make it difficult to assess the histological response to chemotherapy, since the entire tumor cannot be analyzed. Here, we analyzed the prognostic value of the histological response in the patients who received frozen tumor-bearing autografts for reconstruction.
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Prognostic value of radiological response to chemotherapy in patients with osteosarcoma.
PLoS ONE
PUBLISHED: 01-01-2013
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Chemotherapy is essential to improve the prognosis of the patients with osteosarcoma, and the response to chemotherapy is an important prognostic factor. In this study, the impact of various radiological examinations on overall survival (OS) and event-free survival (EFS) was evaluated.
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Comparison of cancer-cell seeding, viability and deformation in the lung, muscle and liver, visualized by subcellular real-time imaging in the live mouse.
Anticancer Res.
PUBLISHED: 11-24-2011
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The comparison of cancer cell seeding, deformation and viability in the lung, muscle and liver of nude mice in real-time is reported here. The mice were intubated to support ventilation with positive end-respiratory pressure (PEEP) for imaging on the lung. Human fibrosarcoma cells with green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm (dual-color HT-1080 cells) were injected into the tail vein for lung imaging, the portal vein for liver imaging or the abdominal aorta for muscle imaging which was performed with an Olympus OV100 Small Animal Imaging System. The length of the cytoplasm and nuclei in 20 seeded cancer cells were measured. A large number of cells initially arrested in the lung capillaries and many cells formed aggregates. The cell number decreased rapidly at 6 and 24 h. There was no significant difference in cancer cell survival when immunocompetent C57BL/6 mice were used in place of the nude mice, suggesting that T cell reaction is not very important in the first 24 h after seeding of cancer cells in the lung. In the lung and liver, little cancer cell deformation occurred. In contrast in the muscle, the cytoplasm and nuclei of the seeded cells were highly deformed and many fragmented cells were observed. The rate of cancer cell death was highest in the lung and lowest in the muscle. In each organ, single disseminated cells tended to die earlier than aggregated cells. The results of this study suggest that the early steps of metastasis are different in the lung, liver and muscle.
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Cryotreatment against metastatic renal cell bone tumour reduced multiple lung metastases.
Anticancer Res.
PUBLISHED: 08-27-2011
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Metastatic renal cell carcinoma (RCC) has a poor response to anticancer chemotherapy and radiotherapy. While immunotherapy and molecular targeted drugs have been used as first-line therapy for RCC metastasis, the response rate to these agents is low. We report the case of a patient with lung and bone metastases of RCC whose lung metastases disappeared after reconstruction using the resected specimen treated by liquid nitrogen for the bone metastasis. This 60-year-old female had a left RCC with multiple lung metastases and a left femoral bone metastasis at the time of diagnosis. After left nephrectomy followed by immunotherapy, we performed tumour excision and reconstruction with frozen recycled autograft. The lung metastases had disappeared by 10 months after surgery, while serum levels of interferon-gamma and interleukin-12 had increased. We postulate that the antitumour activity resulted from immunotherapy plus cryotreatment of her bone metastasis and believe that this case supports continued research into immunotherapy for cancer.
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[Educational usefulness of lung auscultation training with an auscultation simulator].
Nihon Kokyuki Gakkai Zasshi
PUBLISHED: 07-09-2011
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We examined the educational usefulness of lung auscultation training with an auscultation simulator "Mr. Lung".
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Caffeine-potentiated chemotherapy for clear cell sarcoma: a report of five cases.
Int. J. Clin. Oncol.
PUBLISHED: 05-20-2011
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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.
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Activity of bone morphogenetic protein-7 after treatment at various temperatures: freezing vs. pasteurization vs. allograft.
Cryobiology
PUBLISHED: 05-15-2011
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Insufficient bone union is the occasional complication of biomechanical reconstruction after malignant bone tumor resection using temperature treated tumor bearing bone; freezing, pasteurization, and autoclaving. Since bone morphogenetic protein (BMP) plays an important role in bone formation, we assessed the amount and activity of BMP preserved after several temperature treatments, including -196 and -73°C for 20 min, 60 and 100°C for 30 min, 60°C for 10h following -80°C for 12h as an allograft model, and 4°C as the control. The material extracted from the human femoral bone was treated, and the amount of BMP-7 was analyzed using an enzyme-linked immunosorbent assay. Then, the activity of recombinant human BMP-7 after the treatment was assessed using a bioassay with NIH3T3 cells and immunoblotting analysis to measure the amount of phospho-Smad, one of the signaling substrates that reflect the intracellular reaction of BMPs. Both experiments revealed that BMP-7 was significantly better preserved in the hypothermia groups. The percentages of the amount of BMP-7 in which the control group was set at 100% were 114%, 108%, 70%, 49%, and 53% in the -196, -73, 60, 100°C, and the allograft-model group, respectively. The percentages of the amount of phospho-Smad were 89%, 87%, 24%, 4.9%, and 14% in the -196, -73, 60, 100°C, and the allograft-model group, respectively. These results suggested that freezing possibly preserves osteoinductive ability than hyperthermia treatment.
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Functional outcomes after total scapulectomy for malignant bone or soft tissue tumors in the shoulder girdle.
Int. J. Clin. Oncol.
PUBLISHED: 03-17-2011
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The shoulder girdle is a common site for malignant bone and soft tissue tumors. Total scapulectomy represents an attractive alternative to amputation when the whole scapula is invaded with tumor and the neurovascular bundle can be preserved during tumor resection. The purpose of this study was to investigate functional outcomes after total scapulectomy.
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Potentiation of the antitumor effect of calcium phosphate cement containing anticancer drug and caffeine on rat osteosarcoma.
J Orthop Sci
PUBLISHED: 03-01-2011
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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).
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Caffeine activates tumor suppressor PTEN in sarcoma cells.
Int. J. Oncol.
PUBLISHED: 02-09-2011
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The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Akt activation exerts a strong anti-apoptotic effect and inhibits key pro-apoptotic proteins. We investigated the effect of caffeine in the prevention of tumor cell proliferation and induction of cell death. We found that caffeine induced increased intracellular cAMP levels, PTEN activation and Akt inactivation, which together prevented proliferation of human osteosarcoma cells (MG63) and fibrosarcoma cells (HT1080). PTEN knockdown by siRNA reduced the effects of caffeine on Akt inactivation in osteosarcoma cells. These results indicate that the tumor suppressor PTEN signaling pathway contributes to the growth-inhibitory effect of caffeine on sarcoma cells. Our data suggest that caffeine and other drugs that act on this pathway could have promising therapeutic effects in the treatment of sarcoma patients.
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Use of 99mTc-MIBI scintigraphy in the evaluation of the response to chemotherapy for osteosarcoma: comparison with 201Tl scintigraphy and angiography.
Int. J. Clin. Oncol.
PUBLISHED: 01-19-2011
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In the treatment of osteosarcoma, the chemotherapeutic effect influences decisions regarding the surgical margin, continuation of chemotherapy, and choice of anticancer drugs for further chemotherapy. Therefore, it is necessary to evaluate the response to chemotherapy in the middle of the chemotherapy course. In this study, we investigated the use of (99m)Tc-hexakis-2-methoxyisobutyl-isonitrile ((99m)Tc-MIBI) scintigraphy in evaluating the response to chemotherapy of patients with osteosarcoma in comparison with (201)Tl scintigraphy and angiography.
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Desmoplastic small round cell tumour successfully treated with caffeine-assisted chemotherapy: a case report and review of the literature.
Anticancer Res.
PUBLISHED: 10-15-2010
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Desmoplastic small round cell tumour (DSRCT) is a rare tumour, usually arising in the abdominal cavity. DSRCT remains an aggressive malignancy, with a poor prognosis despite multi-modality treatments. In the published literature, there has been no patient who lived for three years or more without surgical excision. This report describes a case of DSRCT arising from the brachial plexus and successfully treated with caffeine-assisted chemotherapy. A 29-year-old male presented with pain and numbness in his left forearm. Radiological findings were suggestive of malignant tumour. Histology, immunohistochemical stain and fluorescence in situ hybridisation (FISH) results confirmed the diagnosis of DSRCT. He underwent caffeine-potentiated chemotherapy and the tumour disappeared. The tumour was not removed surgically as it was intertwined in the brachial plexus. Four years after the initial diagnosis, no local relapse and no distant metastases have been observed. Therefore, it is concluded that caffeine-assisted chemotherapy should be one of the treatment options for DSRCT.
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UV light killing efficacy of fluorescent protein-expressing cancer cells in vitro and in vivo.
J. Cell. Biochem.
PUBLISHED: 05-28-2010
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We investigated the cell-killing efficacy of UV light on cancer cells expressing GFP in the nucleus and RFP in the cytoplasm (dual-color cells). After exposure to various doses of UVA, UVB, or UVC, apoptotic and viable cells were quantitated under fluorescence microscopy using dual-color 143B human osteosarcoma cells, HT-1080 human fibrosarcoma cells, Lewis lung carcinoma (LLC), and XPA-1 human pancreatic cancer cells in vitro. UV-induced cancer cell death was wave-length and dose dependent, as well as cell-line dependent. After UVA exposure, most cells were viable even when the UV dose was increased up to 200 J/m(2). With UVB irradiation, cell death was observed with irradiation at 50 J/m(2). For UVC, as little as 25 J/m(2) UVC irradiation killed approximately 70% of the 143B dual-color cells. This dose of UVB or UVA had almost no effect on the cancer cells. UV-induced cancer cell death varied among the cell lines. Cell death began about 4 h after irradiation and continued until 10 h after irradiation. UVC exposure also suppressed cancer cell growth in nude mice in a model of minimal residual cancer (MRC). No apparent side effects of UVC exposure were observed. This study opens up the possibility of UVC treatment for MRC after surgical resection.
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Pedicle frozen autograft reconstruction in malignant bone tumors.
J Orthop Sci
PUBLISHED: 01-21-2010
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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.
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Comparison of the contents of kampo decoctions containing ephedra herb when prepared simply or by re-boiling according to the traditional theory.
J Nat Med
PUBLISHED: 08-31-2009
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Herbal formulas containing ephedra herb (mao-zai) are among the most important medicinal prescriptions in Japanese traditional kampo medicine to treat cold symptoms, bronchial asthma, arthralgia, and rheumatism. Shokan-zatsubyo-ron (Shanghan zabing lun in Chinese), a classical textbook of kampo medicine published in 220 A.D., describes that when herbal formulas containing ephedra herb (stem of Ephedra sinica) such as maoto (mahuang-tang) and kakkonto (gegen-tang) are prepared, ephedra herb is first boiled alone, the scum is removed, and then other crude drugs are added and decocted. In the present study, we evaluated evidence for the benefit of boiling ephedra herb prior to other crude drugs by analyzing the contents of the extract and four ephedrine alkaloids (ephedrine, methylephedrine, pseudoephedrine, and norephedrine), which are considered the main active ingredients in ephedra herb. We prepared two different decoctions of maoto and kakkonto: one decoction was prepared by boiling all the crude drugs at the same time and the other decoction was prepared according to the classical textbook. In both decoctions of maoto and kakkonto, neither alkaloid contents in the extract nor extracting ratio of four ephedrine alkaloids exhibited significant difference. As far as the ephedrine alkaloid content goes, there is no evidence for the benefit of the boiling method for ephedra herb described in the classical textbook of kampo medicine.
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In vivo internal tumor illumination by telomerase-dependent adenoviral GFP for precise surgical navigation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-17-2009
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Cancer surgery requires the complete and precise identification of malignant tissue margins including the smallest disseminated lesions. Internal green fluorescent protein (GFP) fluorescence can intensely illuminate even single cells but requires GFP sequence transcription within the cell. Introducing and selectively activating the GFP gene in malignant tissue in vivo is made possible by the development of OBP-401, a telomerase-dependent, replication-competent adenovirus expressing GFP. This potentially powerful adjunct to surgical navigation was demonstrated in 2 nude mouse models that represent difficult surgical challenges--the resection of widely disseminated cancer. HCT-116, a model of intraperitoneal disseminated human colon cancer, was labeled by virus injection into the peritoneal cavity. A549, a model of pleural dissemination of human lung cancer, was labeled by virus administered into the pleural cavity. Only the malignant tissue fluoresced brightly in both models. In the intraperitoneal model of disseminated cancer, fluorescence-guided surgery enabled resection of all tumor nodules labeled with GFP by OBP-401. The data in this report suggest that adenoviral-GFP labeling tumors in patients can enable fluorescence-guided surgical navigation.
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In vivo gene transfer between interacting human osteosarcoma cell lines is associated with acquisition of enhanced metastatic potential.
J. Cell. Biochem.
PUBLISHED: 07-23-2009
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We report here in vivo gene transfer between cancer cells is associated with acquisition of high metastatic behavior. The 143B-GFP cell line with high metastatic potential and the MNNG/HOS-RFP cell line with low metastatic potential, both derived from the TE85 human osteosarcoma cell line, were either co-transplanted or transplanted alone in the tibia in nude mice. Upon mixed transplantation of the two differently labeled sublines, resulting metastatic colonies are single colored either red or green, thereby demonstrating their clonality and enabling facile color-coded quantification. When MNNG/HOS-RFP and 143B-GFP were co-transplanted in the tibia, the number of lung metastases of MNNG/HOS-RFP increased eight-fold compared to MNNG/HOS-RFP transplanted alone (P < 0.01). In contrast, no enhancement of MNNG/HOS-RFP metastases occurred when MNNG/HOS-RFP and 143B-GFP were transplanted separately in the right and left tibiae, respectively. This result suggests that the presence of 143B-GFP increased the metastatic potential of MNNG/HOS-RFP within the mixed tumor. We observed transfer of the Ki-ras gene from 143B-GFP to MNNG/HOS-RFP after they were co-implanted suggesting the Ki-ras played a role in increasing the metastatic potential of MNNG/HOS-RFP in the presence of 143B-GFP. These data suggest the possible role of in vivo gene transfer in enhancing the metastatic potential of cancer cells. The data also further demonstrated the power of color-coded imaging to visualize cancer-cell/cancer-cell interactions in vivo.
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Increased rate of death related to presence of viremia among hepatitis C virus antibody-positive subjects in a community-based cohort study.
Hepatology
PUBLISHED: 07-09-2009
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The overall mortality of patients infected with hepatitis C virus (HCV) has not been fully elucidated. This study analyzed mortality in subjects positive for antibody to HCV (anti-HCV) in a community-based, prospective cohort study conducted in an HCV hyperendemic area of Japan. During a 10-year period beginning in 1995, 1125 anti-HCV-seropositive residents of Town C were enrolled into the study and were followed for mortality through 2005. Cause of death was assessed by death certificates. Subjects with detectable HCV core antigen (HCVcAg) or HCV RNA were considered as having hepatitis C viremia and were classified as HCV carriers; subjects who were negative for both HCVcAg and HCV RNA (i.e., viremia-negative) were considered as having had a prior HCV infection and were classified as HCV noncarriers. Among the anti-HCV-positive subjects included in the analysis, 758 (67.4%) were HCV carriers, and 367 were noncarriers. A total of 231 deaths occurred in these subjects over a mean follow-up of 8.2 years: 176 deaths in the HCV carrier group and 55 in the noncarrier group. The overall mortality rate was higher in HCV carriers than in noncarriers, adjusted for age and sex (hazard ratio, 1.53; 95% confidence interval, 1.13-2.07). Although liver-related deaths occurred more frequently among the HCV carriers (hazard ratio, 5.94; 95% confidence interval, 2.58-13.7), the rates of other causes of death did not differ between HCV carriers and noncarriers. Among HCV carriers, a higher level of HCVcAg (>or=100 pg/mL) and persistently elevated alanine aminotransferase levels were important predictors of liver-related mortality. Conclusion: The presence of viremia increases the rate of mortality, primarily due to liver-related death, among anti-HCV-seropositive persons in Japan.
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The complement component C3a fragment is a potential biomarker for hepatitis C virus-related hepatocellular carcinoma.
J. Gastroenterol.
PUBLISHED: 07-01-2009
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Hepatocellular carcinoma (HCC) has a high mortality rate, and early detection of HCC improves patient survival. However, the molecular diagnostic markers for early HCC have not been fully elucidated. The aim of this study was to identify novel diagnostic markers for HCC.
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Efficacy of a genetically-modified Salmonella typhimurium in an orthotopic human pancreatic cancer in nude mice.
Anticancer Res.
PUBLISHED: 06-17-2009
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We report here a tumor-targeting strategy for pancreatic cancer using a modified auxotrophic strain of Salmonella typhimurium. The genetically-modified strain of S. typhimurium requires the amino acids arginine and leucine. These mutations preclude growth in normal tissue but do not reduce bacterial virulence in tumor cells. The tumor-targeting strain of S. typhimurium, termed A1-R and expressing green fluorescent protein (GFP), was administered to an orthotopic human pancreatic tumor expressing red fluorescent protein (RFP) in nude mice. After 7 days of treatment, the pancreatic cancer had regressed without the need of chemotherapy or any other treatment. This new strategy demonstrates the clinical potential of bacterial targeting for pancreatic cancer.
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Histological examination of frozen autograft treated by liquid nitrogen removed after implantation.
J Orthop Sci
PUBLISHED: 04-22-2009
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Several oncological sterilization methods involving autoclaving, irradiation, or pasteurization have been developed for limb reconstruction of large bone defects following tumor excision. Studies involving histological examinations of these autografts have all found that osteogenesis occurs slowly. We have used frozen autografts treated by liquid nitrogen for limb reconstruction and have achieved excellent results for bone union. To determine if frozen autografts exhibit early bone remodeling, we investigated the repair processes of the frozen bones.
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Caffeine-potentiated chemotherapy for metastatic osteosarcoma.
J Orthop Sci
PUBLISHED: 04-15-2009
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The prognosis for patients with metastatic osteosarcoma is still poor despite the development of effective adjuvant and neoadjuvant chemotherapy regimens. We have developed caffeine-potentiated chemotherapy for treatment of high-grade bone and soft tissue sarcomas based on the ability of caffeine to enhance the cytocidal effects of anticancer drugs. We report results of caffeine-potentiated chemotherapy for patients with osteosarcoma with pulmonary metastases.
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Systemic targeting of primary bone tumor and lung metastasis of high-grade osteosarcoma in nude mice with a tumor-selective strain of Salmonella typhimurium.
Cell Cycle
PUBLISHED: 03-20-2009
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We report here a new targeting strategy for primary bone tumor and lung metastasis with a modified auxotrophic strain of Salmonella typhimurium. We have previously developed the genetically-modified strain of S. typhimurium, selected for tumor targeting and therapy in vivo. Normal tissue is cleared of these bacteria even in immunodeficient athymic mice with no apparent side effects. In this study, the tumor-targeting strain of S. typhimurium, termed A1-R, was administered i.v. to nude mice which have primary bone tumor and lung metastasis. Primary bone tumor was obtained by orthotopic intra-tibial injection of 5 x 10(5) 143B-RFP (red fluorescent protein) human osteosarcoma cells. One group of mice was treated with A1-R expressing GFP (green fluorescent protein) and another group was used a as control. A1-R (5 x 10(7) colony-forming units) was injected in the tail vein three times on a weekly basis. On day 28, lung samples were excised and observed with the Olympus OV100 Small Animal Imaging System. The size of the primary tumor and RFP intensity of lung metastasis were measured. Primary bone tumor size (fluorescence area [mm(2)]) was 232 +/- 70 in the untreated group and 95 +/- 23 in the treated group (p < 0.05). RFP intensity of the lung metastasis was 3 +/- 1.5 x 10(6) in the untreated group and 0.42 +/- 0.33 x 10(6) in the treated group (p < 0.05). Therefore, bacterial treatment was effective for both primary bone tumor and lung metastasis.
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Occlusive dressing for large soft tissue defects following soft tissue tumor excision.
J Orthop Sci
PUBLISHED: 03-13-2009
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Reconstructive surgery using pedicles or free muscle-skin flaps and skin grafting reduces wound complications and promotes favorable limb function; however, the sacrifice of normal tissue remains problematic and complicated. Occlusive dressings are widely employed for management of injuries, burns, and surgical wounds. However, their effectiveness for treating soft tissue defects following a soft tissue tumor excision has not been fully elucidated. The purpose of this study was to evaluate the effectiveness and safety of an occlusive dressing treatment method for soft tissue defects following soft tissue tumor excisions.
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Impact of serum caffeine monitoring on adverse effects and chemotherapeutic responses to caffeine-potentiated chemotherapy for osteosarcoma.
J Orthop Sci
PUBLISHED: 02-18-2009
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Caffeine can safely enhance the cytocidal effects of anticancer drugs through its DNA repair-inhibiting effect. We have demonstrated in several studies that caffeine-potentiated chemotherapy induces a high complete response rate in patients with osteosarcoma. The present study focused on monitoring and adjusting serum caffeine levels during caffeine-potentiated chemotherapy to reduce adverse effects.
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Cancer metastasis directly eradicated by targeted therapy with a modified Salmonella typhimurium.
J. Cell. Biochem.
PUBLISHED: 02-10-2009
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Cancer metastasis is the life-threatening aspect of cancer and is usually resistant to standard treatment. We report here a targeted therapy strategy for cancer metastasis using a genetically-modified strain of Salmonella typhimurium. The genetically-modified strain of S. typhimurium is auxotrophic for the amino acids arginine and leucine. These mutations preclude growth in normal tissue but do not reduce bacterial virulence in cancer cells. The tumor-targeting strain of S. typhimurium, termed A1-R, and expressing green fluorescent protein (GFP), was administered to both axillary lymph and popliteal lymph node metastasis of human pancreatic cancer and fibrosarcoma, respectively, as well as lung metastasis of the fibrosarcoma in nude mice. The bacteria were delivered via a lymphatic channel to target the lymph node metastases and systemically via the tail vein to target the lung metastasis. The cancer cells expressed red fluorescent protein (RFP) in the cytoplasm and GFP in the nucleus linked to histone H2B, enabling color-coded real-time imaging of the bacteria targeting the metastatic tumors. After 7-21 days of treatment, the metastases were eradicated without the need of chemotherapy or any other treatment. No adverse effects were observed. This new strategy demonstrates the clinical potential of targeting and curing cancer metastasis with engineered bacteria without the need of toxic chemotherapy.
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Fluorescent LYVE-1 antibody to image dynamically lymphatic trafficking of cancer cells in vivo.
J. Surg. Res.
PUBLISHED: 01-15-2009
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The lymphatic system is a major route for cancer cell dissemination, and a potential target for antitumor therapy. Despite ongoing interest in this area of research, the real-time behavior of cancer cells trafficking in the lymphatic system is poorly understood due to lack of appropriate tools to image this process.
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Monotherapy with a tumor-targeting mutant of S. typhimurium inhibits liver metastasis in a mouse model of pancreatic cancer.
J. Surg. Res.
PUBLISHED: 01-07-2009
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Cancer of the exocrine pancreas is the fourth leading cause of cancer deaths in the United States. Currently, surgical resection is the only hope for cure. The majority of patients present with locally-advanced or metastatic disease. The most common site for distant metastasis is the liver. We report here a modified auxotrophic strain of S. typhimurium that can target and inhibit the growth of liver metastasis in a mouse model of pancreatic cancer. This strain of S. typhimurium is auxotrophic (leucine-arginine dependent) but apparently receives sufficient nutritional support from tumor tissue. To increase tumor targeting ability and tumor killing efficacy, this strain was further modified by re-isolation from a tumor growing in a nude mouse and termed A1-R. In the present study, we demonstrate the efficacy of locally- as well as systemically-administered A1-R on liver metastasis of pancreatic cancer. Mice treated with A1-R given locally via intrasplenic injection or systemically via tail vein injection had a much lower hepatic and splenic tumor burden compared with control mice. Systemic treatment with intravenous A1-R also increased survival time. All results were statistically significant. This study suggests the clinical potential of bacterial treatment of a critical metastatic target of pancreatic cancer.
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TNF-? and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors.
PLoS ONE
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Dendritic cells (DCs) play a pivotal role in the immune system. There are many reports concerning DC-based immunotherapy. The differentiation and maturation of DCs is a critical part of DC-based immunotherapy. We investigated the differentiation and maturation of DCs in response to various stimuli.
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Over 10-year follow-up of functional outcome in patients with bone tumors reconstructed using distraction osteogenesis.
J Orthop Sci
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The aim of this study was to investigate the long-term functional capabilities of patients who underwent bone distraction for the treatment of bone defects caused by bone tumor excision.
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Caffeine induces apoptosis of osteosarcoma cells by inhibiting AKT/mTOR/S6K, NF-?B and MAPK pathways.
Anticancer Res.
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We previously reported that caffeine-assisted chemotherapy improved the treatment of malignant bone and soft tissue tumours such as osteosarcoma. Caffeine affects tumour cells through various pathways, including phosphatase and tensin homolog deleted on chromosome 10 (PTEN), AKT, Bcl-2-associated X protein (BAX), caspase-3 and p53, and has therefore been indicated as being useful for the treatment of malignant tumours. Here, the effects of caffeine on the proliferation of HOS osteosarcoma cells were assessed by WST-8 assay, and the effects on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B), mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) pathways were assessed by western blot analyses. Caffeine inhibited proliferation of HOS cells and suppressed NF-?B, AKT, mTOR/S6K and ERK activities. Our results support those from previous studies relating to the use of caffeine in the treatment of osteosarcoma.
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Uncultured adipose-derived regenerative cells promote peripheral nerve regeneration.
J Orthop Sci
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We examined whether or not peripheral nerves can be regenerated using uncultured adipose-derived regenerative cells (ADRCs). We also searched for humoral factors that might promote the proliferation or migration of Schwann cells.
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Difference in serum complement component C4a levels between hepatitis C virus carriers with persistently normal alanine aminotransferase levels or chronic hepatitis C.
Mol Med Rep
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Certain hepatitis C virus (HCV) carriers exhibit persistently normal alanine aminotransferase (ALT) levels (PNALT) (? 30 IU/l) accompanied by normal platelet counts (? 15 x 10(4)/µl); these individuals show milder disease activity and slower progression to cirrhosis. This study aimed to elucidate the characteristics of HCV carriers with PNALT using serum proteomics. The first group of subjects, who underwent clinical evaluation in the hospital, consisted of 19 HCV carriers with PNALT (PNALT-1) and 20 chronic hepatitis C (CHC-1) patients. The second group of subjects was part of a cohort study on the natural history of liver disease, and included 37 PNALT (PNALT-2) and 30 CHC (CHC-2) patients. Affinity bead-purified serum protein was subjected to matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis. Serum proteomics showed that 6 protein peaks with mass-to-charge ratios ranging from 1,000 to 3,000 differed significantly between the PNALT-1 and CHC-1 groups. Among these peaks, a 1738-m/z peak protein was identified as a fragment of complement component 4 (C4) and correlated significantly with serum C4a concentrations as determined by enzyme immunoassay. Serum C4a levels were also significantly higher in the PNALT-2 group compared to the CHC-2 group and healthy volunteers. Furthermore, in the PNALT-2 group, serum C4a levels negatively correlated with transaminase levels, but not with other biochemical tests, HCV core antigen levels, peripheral blood cell counts or serum hepatic fibrosis markers. This study indicates that host factors such as C4a not only differ between HCV carriers with PNALT and CHC, but that proteomic approaches could also contribute to the elucidation of factors in PNALT as more differences are discovered.
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Treatment strategies for well-differentiated liposarcomas and therapeutic outcomes.
Anticancer Res.
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This study examined 45 patients with well-differentiated liposarcoma who were surgically treated at our hospital (initial surgery in 41 patients and reoperation in 4). Only one patient had recurrence among patients who underwent initial surgery, and the recurrence was localised in the retroperitoneal space. For patients who underwent reoperation, the mean time between the initial surgery and the recurrence was 16.5 years. None of the 45 patients developed distant metastasis. It is important to preserve not only neurovascular bundles but also lower limb muscles in order to maintain ambulatory ability in the elderly patients. For well-differentiated liposarcomas of the limbs, it is important to establish a surgical margin beyond the marginal resection border and to perform muscle resection to the extent that would not greatly reduce the muscle strength.
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A novel combined radiological method for evaluation of the response to chemotherapy for primary bone sarcoma.
J Surg Oncol
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In the treatment of bone sarcoma, evaluation of chemotherapeutic effects is extremely important. In this study, we compared radiological evaluations and histological response, and developed a combined radiological scoring system for assessing the response to chemotherapy.
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Imaging the inhibition by anti-?1 integrin antibody of lung seeding of single osteosarcoma cells in live mice.
Int. J. Cancer
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Integrins play a role in tumor growth and metastasis. However, the effect of integrin inhibition has not been visualized on single cancer cells in vivo. In this study, we used a powerful subcellular in vivo imaging model to demonstrate how an anti-integrin antibody affects seeding and growth of osteosarcoma cells on the lung. The 143B human osteosarcoma cell line, expressing red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nucleus, was established. Such double-labeled cells enable imaging of apoptosis and mitosis and other nuclear-cytoplasmic dynamics. Using the double-labeled osteosarcoma cells, single cancer-cell seeding in the lung after i.v. injection of osteosarcoma cells was imaged. The anti-?1 integrin monoclonal antibody, AIIB2, greatly inhibited the seeding of cancer cells on the lung (experimental metastasis) while a control antibody had no effect. To image the efficacy of the anti-integrin antibody on spontaneous metastasis, mice with orthotopically-growing 143B-RFP cells in the tibia were also treated with AIIB2 or control anti-rat IgG1 antibody. After 3 weeks treatment, mice were sacrificed and primary tumors and lung metastases were evaluated with fluorescence imaging. AIIB2 significantly inhibited spontaneous lung metastasis but not primary tumor growth, possibly due to inhibition of lung seeding of the cancer cells as imaged in the experimental metastasis study. AIIB2 treatment also increased survival of mice with orthotopically growing 143B-RFP.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.