Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells.

BACKGROUND: Osteopontin is a secreted phosphoglycoprotein that is expressed by a number of normal cells as well as a variety of tumor cells. With respect to breast cancer, osteopontin has been implicated in regulating tumor cell proliferation and migration/metastasis and may serve as a prognostic indicator. However it remains unclear whether osteopontin has the same impact in all breast cancer subtypes and in particular, osteopontin's effects in claudin-low breast cancer are poorly understood. METHODS: cDNA microarrays and qRT-PCR were used to evaluate osteopontin expression in mammary tumors from MTB-IGFIR transgenic mice and cell lines derived from these tumors. siRNA was then used to determine the impact of osteopontin knockdown on proliferation, apoptosis and migration in vitro in two murine claudin-low cell lines as well as identify the receptor mediating osteopontin's physiologic effects. RESULTS: Osteopontin was expressed at high levels in mammary tumors derived from MTB-IGFIR transgenic mice compared to normal mammary tissue. Evaluation of cell lines derived from different mammary tumors revealed that mammary tumor cells with claudin-low characteristic expressed high levels of osteopontin whereas mammary tumor cells with mixed luminal and basal-like features expressed lower levels of osteopontin. Reduction of osteopontin levels using siRNA significantly reduced proliferation and migration while increasing apoptosis in the claudin-low cell lines. Osteopontin's effect appear to be mediated through a receptor containing ITGAV and not through CD44. CONCLUSIONS: Our data suggests that mammary tumors with a mixed luminal/basal-like phenotype express high levels of osteopontin however this osteopontin appears to be largely produced by non-tumor cells in the tumor microenvironment. In contrast tumor cells with claudin-low characteristics express high levels of osteopontin and a reduction of osteopontin in these cells impaired proliferation, survival and migration.

The fate of meniscal tears after anterior cruciate ligament reconstruction.

OBJECTIVE: To investigate the incidence of meniscal pathology and subsequent treatment at an index arthroscopically assisted reconstruction of acute ACL tears (<3 weeks after injury) and to determine the outcome of meniscal pathology. DESIGN: Cohort study with average postoperative follow-up of 40 months (range, 24-76 months). SETTING: University-based sports medicine center. PATIENTS: Series of 162 patients admitted between January 1989 and July 1993. Follow-up was obtained for 105 patients. MAIN OUTCOME MEASURES: Initial presence, location, and treatment of meniscal tears. Subsequent surgery performed and further investigation or surgery being planned. RESULTS: Approximately 40% of patients had meniscal pathology at the index procedure. Most tears were in the lateral meniscus (34 of 45). All posterolateral tears and most other small tears were left untreated (25 of 45). Partial meniscectomies were performed on 17 large, complex, or radial tears that were not amenable to meniscal resuturing. Three meniscal repairs were performed on large, unstable tears. Most patients achieved good functional results. Of the five patients who required late meniscal surgery, three had normal menisci at the index procedure. The other two were asymptomatic until experiencing a reinjury. Despite ACL reconstruction in the acute phase, only two patients required treatment for postoperative arthrofibrosis. Three patients required revision ACL reconstruction after return to full activities and experiencing reinjuries. CONCLUSIONS: Stable tears of both lateral and medial menisci remain asymptomatic at 2 to 6 years' follow-up if treated conservatively. Those requiring further surgery had de novo tears or tears that were asymptomatic before reinjury. Although repair may be of benefit for large flap or bucket-handle tears, it does not appear necessary for most tears and may increase the incidence of postoperative stiffness.

Evaluation of cartilage lesions by magnetic resonance imaging at 0.15 T: comparison with anatomy and concordance with arthroscopy.

Recent evidence suggests that pharmacological treatment may alter the rate of progression of cartilage damage in osteoarthritis (OA). However, a lack of accurate and precise noninvasive assessments of cartilage structure makes it difficult to answer this question directly with prospective clinical trials, prevents early diagnosis of OA and restricts assessment of treatment to evaluation of symptoms or joint function. It is important, therefore, to develop precise, noninvasive methods both for diagnosis of early OA before damage is extensive and irreversible and for evaluation of therapeutic effectiveness. Magnetic resonance imaging (MRI) allows for noninvasive, multiplanar body imaging which depends on proton density, flow, and the T1 and T2 relaxation times. Because these variables differ markedly among joint tissues, cartilage erosions are visible with MRI and it should be possible to quantify them. Our objective was to compare MRI with arthroscopy for assessing the depth of lesions in the articular cartilage of human knees to help develop and validate MRI for use in clinical trials designed to assess the effect of therapy on cartilage structure. In the first part of our study, the effect of the MRI pulse sequence variables on the images was evaluated by varying them systematically and comparing the anatomy seen with MRI with that seen at arthroscopy or arthrotomy and with the histology. In the second part, 31 patients were assessed with MRI before arthroscopy. The MRI were graded on a 4-point ordinal scale by 2 observers who were unaware of the clinical diagnosis and compared with findings at arthroscopy which were graded using the same scale.(ABSTRACT TRUNCATED AT 250 WORDS)

Semitendinosus repair augmentation of acute anterior cruciate ligament rupture.

The semitendinosus tendon has been used since 1980 by the senior author (J.P.M) to augment anterior cruciate ligament repair surgery in cases of acute rupture. There are two major criticisms of this technique: first, the semitendinosus tendon lacks adequate tensile strength functionally to replace the normal anterior cruciate ligament; and second, the semitendinosus is an important hamstring muscle, the loss of which has the potential to weaken the dynamic control of the knee. Objective measurement of success or failure of this procedure is provided by KT1000 arthrometer laxity testing for static recovery of stability, and by Cybex isokinetic dynamometer testing of peak torque and fatigue index to evaluate muscular rehabilitation. Thirty-seven patients were examined using these techniques in a standardized protocol at least two years after surgery. Results show excellent return of static stability and near-normal recovery of strength and endurance of quadriceps and hamstring muscles.

Cysts of the lateral meniscus: arthroscopy versus arthroscopy plus open cystectomy.

A retrospective analysis was performed on 32 knees in 31 patients with the diagnosis of cyst of the lateral meniscus. Average follow-up was 41 months, with a range of 16-72 months. Surgical and histological examination demonstrated pathology varying from large meniscal tears with minimal cyst formation to large cysts with no demonstrable meniscal tear. Two theories of etiology emerged: (a) The tear begins in the meniscus and spreads through the periphery. (b) The lesion begins as a compression injury to the vascular periphery and spreads centrally, producing a meniscus tear, or peripherally, producing a cyst, or both. In our series, 20 patients managed by arthroscopic partial meniscectomy and open cystectomy had 80% excellent-good results versus 50% excellent-good results in 12 patients treated with arthroscopy and partial meniscectomy without extraarticular cystectomy. We recommend the following treatment: arthroscopy with a diligent search for a lateral meniscal tear, especially peripherally. If none is found, proceed to extraarticular cystectomy. If a tear is found, remove all unstable meniscal fragments, leaving a rim, if possible, especially adjacent to the popliteus recess, and then proceed to open cystectomy.

Magnetic resonance imaging of the ligaments and menisci of the knee.

Although the technique is still developing and the data are preliminary, MRI will likely be the best noninvasive method for evaluating the ligaments and menisci of the knee. It can provide valuable and accurate information, especially in the acutely injured knee. The presence, extent, and exact location of cruciate ligament disruption can be visualized. This is useful in patients in whom the clinical diagnosis is uncertain and provides valuable information in preoperative planning. Equally important is the ability of MRI to provide diagnostic information about associated injuries to the collateral ligaments, capsule, menisci, articular cartilage, and subchondral bone. Proper pulse sequence selection is important. T2-weighted spin-echo sequences are best for visualizing injuries to the ligaments and menisci, and T1-weighted sequences (inversion-recovery or spin-echo with a short TR and a short TE) are more helpful in evaluating cartilaginous and bony abnormalities.

Sensitivity response of channel electron multipliers and channel plates to the polarization of VUV radiation.

It is demonstrated that both channel electron multipliers and channel plates may display pronounced polarization sensitivity when VUV radiation is being detected. Photon angle of incidence is demonstrated to be an important parameter for channel plates.