Semaphorin 7a exerts pleiotropic effects to promote breast tumor progression.

Understanding what drives breast tumor progression is of utmost importance for blocking tumor metastasis; we have identified that semaphorin 7a is a potent driver of ductal carcinoma in situ (DCIS) progression. Semaphorin 7a is a glycophosphatidylinositol membrane-anchored protein that promotes attachment and spreading in multiple cell types. Here, we show that increased expression of SEMA7A occurs in a large percentage of breast cancers and is associated with decreased overall and distant metastasis-free survival. In both in vitro and in vivo models, short hairpin-mediated silencing of SEMA7A reveals roles for semaphorin 7a in the promotion of DCIS growth, motility and invasion as well as lymphangiogenesis in the tumor microenvironment. Our studies also uncover a relationship between COX-2 and semaphorin 7a expression and suggest that semaphorin 7a promotes tumor cell invasion on collagen and lymphangiogenesis via activation of ß1-integrin receptor. Our results suggest that semaphorin 7a may be novel target for blocking breast tumor progression.

XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer.

The limitations of cancer cell lines have led to the development of direct patient-derived xenograft models. However, the interplay between the implanted human cancer cells and recruited mouse stromal and immune cells alters the tumor microenvironment and limits the value of these models. To overcome these constraints, we have developed a technique to expand human hematopoietic stem and progenitor cells (HSPCs) and use them to reconstitute the radiation-depleted bone marrow of a NOD/SCID/IL2rg(-/-) (NSG) mouse on which a patient's tumor is then transplanted (XactMice). The human HSPCs produce immune cells that home into the tumor and help replicate its natural microenvironment. Despite previous passage on nude mice, the expression of epithelial, stromal and immune genes in XactMice tumors aligns more closely to that of the patient tumor than to those grown in non-humanized mice-an effect partially facilitated by human cytokines expressed by both the HSPC progeny and the tumor cells. The human immune and stromal cells produced in the XactMice can help recapitulate the microenvironment of an implanted xenograft, reverse the initial genetic drift seen after passage on non-humanized mice and provide a more accurate tumor model to guide patient treatment.

Arthroscopic repair of partial-thickness tears of the rotator cuff.

Management of partial-thickness tears of the rotator cuff should include consideration of tear size, tear depth, patient age and activity level, and tear etiology. We present an arthroscopic technique for repair of articular surface partial-thickness tears that may promote healing by closing the tendon side-to-side, placing the debrided tendon end in contact with an abraded humeral surface. By repairing selected partial-thickness tears, progression of the tear and the need for subsequent repair may be prevented. Our preliminary results in 28 patients are encouraging and suggest that this technique is a useful adjunct to tendon debridement for articular surface partial-thickness tears of the rotator cuff.

Laser-assisted capsulorrhaphy for multidirectional instability of the shoulder.

PURPOSE: The purpose of this study was to review the clinical results of laser-assisted capsulorrhaphy performed on 27 shoulders in 26 patients for multidirectional shoulder instability with minimum follow-up of 2 years. TYPE OF STUDY: Prospective case series. METHODS: Laser shrinkage was performed on the entire capsule. In patients in whom the rotator interval did not shrink, suture plication of this area was performed. All patients were evaluated with respect to the incidence of recurrent instability, need for reoperation, and ability to return to their previous level of activity or sports participation. In addition, all patients were rated as satisfactory or unsatisfactory using criteria established by Neer. RESULTS: Twenty-six of 27 shoulders (96%) remained stable and asymptomatic a minimum of 2 years after surgery. Of 14 athletes in the study group, 12 (86%) returned to their previous level of sports participation. CONCLUSION: Our results suggest that laser-assisted capsulorrhaphy is an effective treatment alternative for multidirectional instability.

The use of a modular rotating hinge component in salvage revision total knee arthroplasty.

Revision total knee arthroplasty (TKA) using a second-generation modular rotating hinge design was performed on 16 knees in 15 patients over a 5-year period. Follow-up of 2 to 6 years (mean, 51 months) was obtained in 14 knees in 13 patients. Indications for revision were aseptic loosening of a hinged prosthesis (8 knees), loosening and bone loss associated with chronic extensor mechanism disruption (2 knees), component instability with chronic medial collateral ligament disruption (3 knees), and comminuted distal femur fracture (1 knee). Clinical and radiographic results were reviewed and compared with 87 patients who underwent revision TKA using a standard condylar revision design during the same period. Early results showed comparable postoperative knee scores and range of motion between the 2 groups despite the use of the rotating hinge component in more complex revision cases. No patient has exhibited radiographic evidence of definite component loosening. Alignment of 5 degrees to 10 degrees of valgus in the frontal plane and within 2 degrees of neutral in the sagittal plane was achieved consistently. Short-term clinical and radiographic results are encouraging and suggest that a second-generation modular rotating hinge component can be used successfully in selected salvage revision cases.

Basics of elbow arthroscopy.

With more innovation in arthroscopic equipment and surgical technique, elbow arthroscopy will continue to evolve and new indications will emerge. Strict adherence to the principles outlined above will allow the use of arthroscopy to treat a variety of elbow disorders in a safe and effective manner.

Archeological methodology and remote sensing.

We have shown that the different spectral surveying techniques and the resultant imagery vary in their applicability to archeological prediction and exploration, but their applications are far broader than we have indicated. Their full potential, to a considerable extent, still remains unexplored. Table 1 is a chart of the more common sensor systems useful to archeological investigators. Several kinds of photography, thermal infrared imagery, and radar imagery are listed. Checks in various categories of direct and indirect utility in archeological research indicate that the different systems do provide varying degrees of input for studies in these areas. Photography and multispectral photography have the broadest applications in this field. Standard black-and-white aerial photography generally serves the purposes of archeological exploration and site analysis better than infrared scanner imagery, radar, or color photography. However, the real value of remotesensing experimentation lies in the utilization of different instruments and in the comparison and correlation of their data output. It can be stated without doubt that there is no one all-purpose remotesensing device on which the archeologist can rely that will reveal all evidence of human occupations. Remote-sensing data will not replace the traditional ground-based site survey, but, used judiciously, data gathered from aerial reconnaissance can reveal many cultural features unsuspected from the ground. The spectral properties of sites distinguishable by various types of remote sensors may perhaps be one of their most characteristic features, and yet the meaning of the differential discrimnination of features has not been determined for the most part, since such spectral properties are poorly understood at this date. The difficulty in isolating the causes of acceptable definition in certain portion of the spectrum and the lack of acceptable definition in others suggests that the evaluation of remote-sensing devices discussed in this article is not always applicable to all environmental zones at all times and for all types of cultural features. The uncontrollable variables of terrain, ground cover, weather, types of archeological manifestations, and other factors all play an important role in the utility of the imagery to the archeologist. Factors within the control of the photographer or archeolgist, such as altitude, position of the sun, and the direction of flight, can greatly influence the utility of the sensor data. In addition, the variables should not be considered solely as they affect resolution. Resolution, per se, although an important photogrammetric parameter of remote-sensing imagery, is by no means the only important factor in data analysis. The synoptic overview, which is provided by aerial imagery, is frequently as necessary in interpretation as the spotting and identification of individual cultural features. Stated more simply, we might say: "To understand, one most certainly must see the forest as well as the individual trees." For maximum data retrieval, it is necessary that the archeologist attempt to utilize as many different types of remote-sensing devices under as many variable seasonal and climatic conditions as his resources and skill will allow. Only then he can select the most efficient system for the purpose in his area of study.