Abstract: Background. We report on 19 cases of giant cell tumor of bone (GCT) affecting the spine or sacrum and evaluate the outcome of different treatment modalities. Methods. Nineteen patients with GCT of the spine (n = 6) or sacrum (n = 13) have been included in this study. The mean followup was 51.6 months. Ten sacral GCT were treated by intralesional procedures of which 4 also received embolization, and 3 with irradiation only. All spinal GCT were surgically treated. Results. Two (15.4%) patients with sacral and 4 (66.7%) with spinal tumors had a local recurrence, two of the letter developed pulmonary metastases. One local recurrence of the spine was successfully treated by serial arterial embolization, a procedure previously described only for sacral tumors. At last followup, 9 patients had no evidence of disease, 8 had stable disease, 1 had progressive disease, 1 died due to disease. Six patients had neurological deficits. Conclusions. GCT of the axial skeleton have a high local recurrence rate. Neurological deficits are common. En-bloc spondylectomy combined with embolization is the treatment of choice. In case of inoperability, serial arterial embolization seems to be an alternative not only for sacral but also for spinal tumors.
Abstract: The aim of this study was to define the treatment criteria for patients with recurrent chondrosarcoma. We reviewed the data of 77 patients to examine the influence of factors such as the intention of treatment (curative/palliative), extent of surgery, resection margins, status of disease at the time of local recurrence and the grade of the tumour. A total of 70Â patients underwent surgery for recurrent chondrosarcoma. In seven patients surgery was not a viable option. Metastatic disease occurred in 41 patients, appearing synchronously with the local recurrence in 56% of cases. For patients without metastasis at the time of local recurrence, the overall survival at a mean follow-up after recurrence of 67 months (0 to 289) was 74% (5 of 27) compared with 19% (13 of 50) for patients with metastasis at or before the development of the recurrence. Neither the type/extent of surgery, site of tumour, nor the resection margins for the recurrent tumour significantly influenced the overall survival. With limited survival for patients with metastatic disease at the time of local recurrence (0% for patients with grade III and de-differentiated chondrosarcoma), palliative treatment, including local radiation therapy and debulking procedures, should be discussed with the patients to avoid long hospitalisation and functional deficits. For patients without metastasis at the time of local recurrence, the overall survival of 74% justifies an aggressive approach including wide resection margins and extensive reconstruction.
Abstract: Calcifying tendinitis is a common and painful disorder of the shoulder characterized by the presence of calcific deposits in the tendons of the rotator cuff. When nonoperative treatment over a prolonged period of time fails, surgical treatment should be considered. Midterm success rates are inconsistent, and the role of subacromial decompression is still unclear.
Abstract: INTRODUCTION: Over the last decade, proprioceptive function gained increasing attention in joint disorders such as instability of the shoulder. Common tests for evaluation of proprioception are limited by their complexity and high technical demands. Thus, they are hardly applicable during daily routine. Our hypothesis was that the simplified "laser-pointer assisted angle reproduction test" (LP-ART) presented here allows for clinically feasible assessment of proprioceptive shoulder function. METHODS: Active angle reproduction capability as an aspect of sensorimotor function was evaluated with the new method in patients with shoulder instability (n = 24) and healthy controls (n = 24). 15 patients had traumatic, 9 non-traumatic anterior instability (6 bilateral), 17 were treated surgically, 13 non-operatively. Tests were performed in flexion and abduction in different angles (55°, 90°, 125°) in randomized order. RESULTS: Angle reproduction capability was worst below shoulder level (55°) in all groups. Best results were achieved at shoulder level (90°). Healthy controls showed overall better results than patients with instability. Patients after surgical stabilization had better results in 55° and 90° abduction compared to instability patients before surgery. CONCLUSIONS: The new LP-ART presented here is a technically simple, yet effective instrument for evaluation of the proprioceptive function of the shoulder. In contrast to former test setups it is feasible in daily routine. Compared to healthy controls, patients with unstable shoulder joints show significant proprioceptive disorders that can be quantified by the LP-ART.
Abstract: ABSTRACT: BACKGROUND: Because of the lack of suitable in vivo models of giant cell tumor of bone (GCT), little is known about its underlying fundamental pro-tumoral events, such as tumor growth, invasion, angiogenesis and metastasis. There is no existing cell line that contains all the cell and tissue tumor components of GCT and thus in vitro testing of anti-tumor agents on GCT is not possible. In this study we have characterized a new method of growing a GCT tumor on a chick chorio-allantoic membrane (CAM) for this purpose. METHODS: Fresh tumor tissue was obtained from 10 patients and homogenized. The suspension was grafted onto the CAM at day 10 of development. The growth process was monitored by daily observation and photo documentation using in vivo biomicroscopy. After 6 days, samples were fixed and further analyzed using standard histology (hematoxylin and eosin stains), Ki67 staining and fluorescence in situ hybridization (FISH). RESULTS: The suspension of all 10 patients formed solid tumors when grafted on the CAM. In vivo microscopy and standard histology revealed a rich vascularization of the tumors. The tumors were composed of the typical components of GCT, including (CD51+/CD68+) multinucleated giant cells which were generally less numerous and contained fewer nuclei than in the original tumors. Ki67 staining revealed a very low proliferation rate. The FISH demonstrated that the tumors were composed of human cells interspersed with chick-derived capillaries. CONCLUSIONS: A reliable protocol for grafting of human GCT onto the chick chorio-allantoic membrane is established. This is the first in vivo model for giant cell tumors of bone which opens new perspectives to study this disease and to test new therapeutical agents.
Abstract: PURPOSE: The aim of this study was to validate the precision of navigated tunnel positioning using a fluoroscopy-based computer-assisted technique. METHODS: Ten human cadaveric knees were operated on under operating room conditions. After resection of the anterior cruciate ligament, referenced fluoroscopic images were acquired to plan the tunnel positions according to established radiologic measurement methods. Afterward, femoral and tibial K-wires were placed by use of navigated drill guides without arthroscopic control. Deviations between the planned and actually drilled tunnel positions at the joint level were analyzed by use of both navigated and radiologic assessment methods. RESULTS: Navigated analysis between planned and actually drilled tunnel position showed mean deviations of 0.4 mm (range, 0 to 1 mm; SD, 0.52 mm) at the femur and 0.5 mm (range, 0 to 1 mm; SD, 0.5 mm) at the tibia. The radiologic analysis showed mean deviations for the femoral tunnel of 0.83 mm for the depth (range, 0 to 1.46 mm; SD, 0.46 mm) and 0.54 mm for the height (range, 0 to 1.08 mm; SD, 0.41 mm). At the tibia, deviation of 0.74 mm (range, 0 to 1.2 mm; SD, 0.46 mm) was found. CONCLUSIONS: The fluoroscopy-based navigation system used in this study allows for precise tunnel positioning with deviations of 1 mm or less. CLINICAL RELEVANCE: This technique provides accurate tunnel placement in anterior cruciate ligament surgery.
Abstract: ABSTRACT: A 56-year-old man presented with a two month history of increasing anterior knee pain without previous trauma. As usual we recommended physiotherapy with stretching exercises of the quadriceps muscle. Since symptoms did not improve after 6 weeks MRI was performed. Surprisingly a hyperintense lobulated mass of the patella with small fluid-filled cavities at the inferior pole was revealed. We performed an open biopsy to exclude any malignancy and diagnosed an aneurysmal bone cyst. Further examination with CT scans showed an aggressive behaviour with cortical breakthrough.We performed an intralesional curettage with additional high-speed burring and bone cement packing. Sixteen months later the patient was free from any complaints and without signs of local recurrence.Primary bone tumors of the patella are extremely rare and occurrence of aneurysmal bone cysts in this localization is very uncommon. This case report indicates that although anterior knee pain is a very frequent and usually harmless symptom, it is essential to consider that it might also be caused by more severe disorders such as bone tumors.
Abstract: There is clinical evidence that a standardized management of trauma patients in the emergency room improves outcome. ATLS(R) is a training course that teaches a systematic approach to the trauma patient in the emergency room. The aims are a rapid and accurate assessment of the patient's physiologic status, treatment according to priorities, and making decisions on whether the local resources are sufficient for adequate definitive treatment of the patient or if transfer to a trauma center is necessary. Above all it is important to prevent secondary injury, to realize timing as a relevant factor in the initial treatment, and to assure a high standard of care. A standard operating procedure (SOP) exactly regulates the approach to trauma patients and determines the responsibilities of the involved faculties. An SOP moreover incorporates the organizational structure in the treatment of trauma patients as well as the necessary technical equipment and staff requirements. To optimize process and result quality, priorities are in the fields of medical fundamentals of trauma care, education, and fault management.SOPs and training courses increase the process and result quality in the treatment of the trauma patient in the emergency room. These programs should be based on the special demands of the physiology of the trauma as well as the structural specifics of the hospital. ATLS(R) does not equal an SOP but it qualifies as a standardized concept for management of trauma patients in the emergency room.
Abstract: ABSTRACT: BACKGROUND: The chick chorio-allantoic membrane (CAM) assay is a commonly used method for studying angiogenic or anti-angiogenic activities in vivo. The ease of access allows direct monitoring of tumour growth by biomicroscopy and the possibility to screen many samples in an inexpensive way. The CAM model provides a powerful tool to study effects of molecules, which interfere with physiological angiogenesis, or experimental tumours derived from cancer cell lines. We therefore screened eight osteosarcoma cell lines for their ability to form vascularized tumours on the CAM. FINDINGS: We implanted 3-5 million cells of human osteosarcoma lines (HOS, MG63, MNNG-HOS, OST, SAOS, SJSA1, U2OS, ZK58) on the CAM at day 10 of embryonic development. Tumour growth was monitored by in vivo biomicroscopy at different time points and tumours were fixed in paraformaldehyde seven days after cell grafting. The tissue was observed, photographed and selected cases were further analyzed using standard histology.From the eight cell lines the MNNG-HOS, U2OS and SAOS were able to form solid tumours when grafted on the CAM. The MNNG-HOS tumours showed the most reliable and consistent growth and were able to penetrate the chorionic epithelium, grow in the CAM stroma and induce a strong angiogenic response. CONCLUSIONS: Our results show that the CAM assay is a useful tool for studying osteosarcoma growth. The model provides an excellent alternative to current rodent models and could serve as a preclinical screening assay for anticancer molecules. It might increase the speed and efficacy of the development of new drugs for the treatment of osteosarcoma.
Abstract: ABSTRACT: Aplasia of both cruciate ligaments is a rare congenital disorder. A 28-year-old male presented with pain and the feeling of instability of his right knee after trauma. The provided MRI and previous arthroscopy reports did not indicate any abnormalities except cruciate ligament tears. He was referred to us for reconstruction of both cruciate ligaments. The patient again underwent arthroscopy which revealed a hypoplasia of the medial trochlea and an extremely narrow intercondylar notch. The tibia revealed a missing anterior cruciate ligament (ACL) footprint and a single bump with a complete coverage with articular cartilage. There was no room for an ACL graft. A posterior cruciate ligament could not be identified. The procedure was ended since a ligament reconstruction did not appear reasonable. A significant notch plasty if not a partial resection of the condyles would have been necessary to implant a ligament graft. It is most likely that this would not lead to good knee stability. If the surgeon would have retrieved the contralateral hamstrings at the beginning of the planned ligament reconstruction a significant damage would have occurred to the patient. Even in seemingly clear diagnostic findings the arthroscopic surgeon should take this rare abdnormality into consideration and be familiar with the respective radiological findings. We refer the abnormal finding of only one tibial spine to as the "dromedar-sign" as opposed to the two (medial and a lateral) tibial spines in a normal knee. This may be used as a hint for aplasia of the cruciate ligaments.
Abstract: BACKGROUND AND OBJECTIVES: The placement of megaprostheses in patients with bone sarcoma is associated with high rates of infection, despite prophylactic antibiotic administration. In individual cases, secondary amputation is unavoidable in the effort to cure infection. METHODS: The infection rate in 51 patients with sarcoma (proximal femur, n = 22; proximal tibia, n = 29) who underwent placement of a silver-coated megaprosthesis was assessed prospectively over a 5-year period, along with the treatment administered for infection. The infection rate was compared with the data for 74 patients in whom an uncoated titanium megaprosthesis (proximal femur, n = 33; proximal tibia, n = 41) was implanted. RESULTS: The infection rate was substantially reduced from 17.6% in the titanium to 5.9% in the silver group. Whereas 38.5% of patients in the titanium group ultimately had to undergo amputation when periprosthetic infection developed, these mutilating surgical procedures were not necessary in the study group. CONCLUSIONS: The use of silver-coated prostheses reduced the infection rate in the medium term. In addition, less aggressive treatment of infection was possible in the group with silver-coated prostheses. Further studies with longer term follow-up periods and larger numbers of patients are warranted in order to confirm these encouraging results.
Abstract: ABSTRACT: BACKGROUND: Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour which contains numerous osteoclast-like giant cells. GCTB frequently recurs and can produce metastatic lesions in the lungs. Bisphosphonates are anti-resorptive drugs which act mainly on osteoclasts. Method: In this study, we have examined clinical and radiological outcomes of treatment with aminobisphosphonates on 25 cases of aggressive primary, recurrent and metastatic GCTB derived from four European centres. We also analysed in vitro the inhibitory effect of zoledronic acid on osteoclasts isolated from GCTBs. Results: Treatment protocols differed with several different aminobisphosphonates being employed, but stabilisation of disease was achieved in most of these cases which were refractory to conventional treatment. Most inoperable sacral/pelvic tumours did not increase in size and no further recurrence was seen in GCTBs that had repeatedly recurred in bone and soft tissues. Lung metastases did not increase in size or number following treatment. Zoledronic acid markedly inhibited lacunar resorption by GCTB-derived osteoclasts in vitro. Conclusion: Our findings suggest that bisphosphonates may be useful in controlling disease progression in GCTB and that these agents directly inhibit GCTB - derived osteoclast resorption. These studies highlight the need for the establishment of standardised protocols to assess the efficacy of bisphosphonate treatment of GCTB.
Abstract: The surgical treatment of low-grade chondrosarcoma is controversial and the clinical course is difficult to predict. The purpose of this retrospective study was to review the authors' experience with the surgical treatment of 80 patients with grade I chondrosarcoma. Intralesional resection margins increased the rate of local recurrence statistically significant (p < 0.001). However, there was no influence of the resection margins on the overall survival (p > 0.05) or on the rate of metastasis (p > 0.05). Conservative surgery for special indications with adjuvant use of PMMA (poly-methylmethacrylate) offers satisfying local tumour control rates in the long bones. However, after intralesional tumour resection of pelvic chondrosarcoma, four out of four patients developed a local recurrence, whereas no patient treated with wide resection margins received a local relapse, which has been statistically significant (p < 0.001). In conclusion, intralesional resection of a grade I chondrosarcoma has a higher overall risk of local recurrence but is not associated with a poorer survival. This procedure can be recommended for stage I A tumours of the long bones of the extremities. However, in pelvic lesions it should be avoided because of a 100% recurrence rate.
Abstract: AIM: Today, megaendoprostheses--which were originally designed for osseous defect reconstructions in tumour surgery--are being more frequently used for extensive bone defects in revision arthroplasty. The purpose of this study was to assess the complication rate and the functional results associated with megaendoprosthesis reconstruction of the proximal femur in a non-oncological patient group. METHOD: 28 patients (average age 72; SD 10 years) with a proximal femur replacement were retrospectively (mean follow-up 43 months) evaluated regarding the complication rate. The Harris hip score was used to assess the outcome. The revision surgery was indicated because of large bone defects caused by implant-associated infection (n = 16), periprosthetic fracture (n = 8) or aseptic loosening (n = 4). RESULTS: Overall 8 patients (28.6 %) had to undergo 1 (n = 5) or more (2 n = 2, 4 n = 1) revision surgeries because of dislocation (n = 4), aseptic loosening of the stem (n = 2) and periprosthetic infection (n = 2). A significant pain relief could be achieved from on average 9.0 to 38.7 (according to the Harris hip score). All patients could be mobilised postoperatively, but walking aids were necessary for the majority of patients. CONCLUSION: A proximal femur replacement in revision arthroplasty should be regarded as a salvage procedure for restoration of extremity function. With this procedure it is possible to achieve a--limited--walking ability for patients who were immobilised preoperatively in most cases. Furthermore, pain relief can be achieved. However, the--mostly multimorbid--patients must be informed preoperatively about restrictions in daily life in order to avoid exorbitant expectations.
Abstract: In long-term survivors, oncologic surgeons are regularly faced with the problem of revising stem breakage of first generation Kotz modular femoral and tibial reconstruction system (KMFTR) prostheses. To avoid a whole prosthesis-exchange, we invented an adapter which allows connecting original KMFTR devices to new modular universal tumor and revision system (MUTARS) components. The adapter was used in 10 patients after a mean time span of 16.6 years after primary implantation of KMFTR prostheses. Reasons for revision included femoral stem breakage in five cases, breakage of tibial component in three cases and periprosthetic fracture in two cases (one femoral, one tibial). The femoral stem (three cases), the tibial stem (two cases) or the tibial plateau and body (two cases) were exchanged to MUTARS and connected to the remaining KMFTR parts. Three cases were converted to a total femur. Postoperative complications included one cone-dislocation and one aseptic loosening. In all patients, the pre-incidence function could be restored. The mean Musculoskeletal Tumor Society score was 81.7% of normal function. The presented adapter enables restoration of the long-term extremity function with relatively minor revision.
Abstract: BACKGROUND AND PURPOSE: Giant cell tumors (GCTs) of bone rarely affect the pelvis. We report on 20 cases that have been treated at our institution during the last 20 years. METHODS: 20 patients with histologically benign GCT of the pelvis were included in this study. 9 tumors were primarily located in the iliosacral area, 6 in the acetabular area, and 5 in the ischiopubic area. 8 patients were treated by intralesional curettage and 6 by intralesional resection with additional curettage of the margins. 3 patients with iliacal tumors were treated by wide resection. 2 patients were treated by a combination of external beam irradiation and surgery, and 1 patient solely by irradiation. In addition, 9 patients received selective arterial embolization one day before surgery. Of the 6 patients with acetabular tumors, 1 secondarily received an endoprosthesis and 1 was primarily treated by hip transposition. The patients were followed for a median time of 3 (1-11) years. RESULTS: 1 patient with a pubic tumor developed a local recurrence 1 year after intralesional resection and additional curettage of the margins. The recurrence presented as a small soft tissue mass within the scar tissue of the gluteal muscles and was treated by resection. No secondary sarcoma was detected and none of the patients developed pulmonary metastases or multicentricity. No major complication occurred during surgery. INTERPRETATION: We conclude that most GCTs of the pelvis can be treated by intralesional procedures. For tumors of the iliac wing, wide resection can be an alternative. Surgical treatment of tumors affecting the acetabular region often results in functional impairment. Pre-surgical selective arterial embolization appears to be a safe procedure that may reduce the risk of local recurrence.
Abstract: Modular tumor prostheses are well established today for the reconstruction of osseous defects after resection of malignant bone tumors. Almost every joint and even total bones (e.g., total femur or humerus) can be replaced with promising functional results, dramatically reducing the need for ablative procedures. Although the complication rate with the use of modern modular endoprostheses is constantly decreasing, the need for revision surgery is still significantly higher than in primary joint arthroplasty. In this review we present the modular endoprosthesis system developed in our institution, summarize the postoperative management, and discuss the indications, limits, and complications as well as the functional results.
Abstract: BACKGROUND: Although the recurrence rate of giant cell tumors of bone (GCTB) is relatively high exact data on treatment options for the recurrent cases is lacking. The possible surgical procedures range from repeated intralesional curettage to wide resection. METHODS: Two hundred and fourteen patients with histologically certified GCTB have been treated at the authors department from 1980 to 2007. Sixty-seven patients with at least one local recurrence were included in this study. The mean follow-up was 77.3 months. The data was evaluated according the re-recurrence rate with regard to the surgical procedure for the recurrence. RESULTS: The mean time until the first local recurrence was 22.0 months; the mean number of recurrences per patient was 1.4. The recurrence occurred in 69.7% (46 out of 66 patients) within the first 2 years. If after intralesional procedures (curettage or intralesional resection) no adjunct was used the re-recurrence rate was 58.8% (10 out of 17 patients) and decreased to 21.7% (5 out of 23 patients) if a combination of all adjuncts (PMMA + burring) was used. The likelihood of re-recurrence was reduced by the factor 5.508 which was clearly significant (P = 0.016). In case of wide resection no re-recurrence occurred. Seven patients (10.5%) developed pulmonary metastases. Fourteen patients (20.9%) finally received an endoprosthesis; 12 due to tumor recurrence, 2 due to secondary arthritis. CONCLUSION: Recurrent GCTB can be treated by further curettage with additional burring and cementing with an acceptable re-recurrence rate of 21.7%. The rate of patients finally needing an endoprosthesis is 20.9%. Due to the high rate of pulmonary metastases recurrent GCTB may be considered as a severe disease.
Abstract: A 72-year-old woman presented with pain, swelling, and decreased range of motion of the left knee joint after total knee arthroplasty in 2005. We performed standard x-rays, which were highly suspicious for an osteosarcoma of the distal femur; this was proven by open biopsy. Retrospectively, the x-rays taken before implantation of the prosthesis showed suspicious findings. Because the femur was tumor-contaminated, with the intramedullary adjustment far-reaching proximally, a limb salvage procedure was no longer possible. To improve function, we decided to perform a stump-lengthening procedure using a special implant. With regard to the dismal consequences, we recommend that every suspicious finding before an elective surgical procedure be examined with further diagnostics and, if necessary, histological confirmation.
Abstract: BACKGROUND: Two hundred and fourteen patients with benign giant cell tumor of bone (GCTB), treated from 1980 to 2007 at the Department of Orthopedics of the University of Muenster (Germany), were analyzed in a retrospective study. PATIENTS AND METHODS: The mean age was 33.3 years with a female-to-male ratio of 1.2 : 1. The mean follow up was 59.8 months. The recurrence rate of patients who received first treatment at our institution was 16.6%. The most common primary treatment was curettage (188 patients) usually followed by adjuvant local therapy. The effects of bone cement (PMMA), burring and hydrogen peroxide (H(2)O(2)) were statistically analyzed and the influence of a subchondral bone graft on the recurrence rate was evaluated. RESULTS: PMMA alone (n = 52) reduces the likelihood of recurrence by the factor 8.2, additional high-speed burring (n = 39) by the factor 3.9 (compared to PMMA only). H(2)O(2) (n = 42) seems to have an additional effect comparable to that of phenol although it did not reach statistical significance. CONCLUSION: The combination of all adjuncts (PMMA, burring, H(2)O(2) - n = 42) reduces the likelihood of recurrence by the factor 28.2 compared to curettage only and therefore should be recommended as a standard treatment. If the tumor reaches close to the articulating surface a subchondral bone graft (n = 42) can be performed without risking a higher recurrence rate. We add seven cases of pulmonary metastases and two cases of multicentricity to the literature. Bisphosphonates and interferon alpha may have a beneficial effect.
Abstract: Biological activities of vascular endothelial growth factor (VEGF) have been studied extensively in endothelial cells (ECs), but few data are available regarding its effects on pericytes. In murine embryoid body cultures, VEGF-induced expression of desmin and alpha-smooth muscle actin (alpha-SMA) in CD-31+ cells. The number of CD-31+/desmin+ vascular chords increased with VEGF treatment time and peaked during a differentiation window between 6 and 9 days after plating. In vivo, VEGF-induced elongation and migration of desmin-positive pericytes and coverage of angiogenic capillaries, as revealed by analysis of Sambucus nigra lectin-stained vascular beds of the chick chorioallantoic membrane. VEGF also caused significant decrease of intercapillary spaces, an indicator for intussusceptive vascular growth. These VEGF-mediated effects point at a more intricate interaction between ECs and pericytes cells than previously demonstrated and suggest that pericytes may be derived from EC progenitors in vitro and not only stabilize capillaries but also participate in vascular remodeling in vivo.
Abstract: Blocking angiogenesis is an attractive strategy to inhibit tumor growth, invasion, and metastasis. We describe here the structure and the biological action of a new cyclic peptide derived from vascular endothelial growth factor (VEGF). This 17-amino acid molecule designated cyclopeptidic vascular endothelial growth inhibitor (cyclo-VEGI, CBO-P11) encompasses residues 79-93 of VEGF which are involved in the interaction with VEGF receptor-2. In aqueous solution, cyclo-VEGI presents a propensity to adopt a helix conformation that was largely unexpected because only beta-sheet structures or random coil conformations have been observed for macrocyclic peptides. Cyclo-VEGI inhibits binding of iodinated VEGF165 to endothelial cells, endothelial cells proliferation, migration, and signaling induced by VEGF165. This peptide also exhibits anti-angiogenic activity in vivo on the differentiated chicken chorioallantoic membrane. Furthermore, cyclo-VEGI significantly blocks the growth of established intracranial glioma in nude and syngeneic mice and improves survival without side effects. Taken together, these results suggest that cyclo-VEGI is an attractive candidate for the development of novel angiogenesis inhibitor molecules useful for the treatment of cancer and other angiogenesis-related diseases.
