Gr-1+CD11b+ cells are responsible for tumor promoting effect of TGF-β in breast cancer progression

One great challenge in our understanding of TGF-β cancer biology and the successful application of TGF-β-targeted therapy is that TGF-β works as both a tumor suppressor and a tumor promoter. The underlying mechanisms for its functional change remain to be elucidated. Using 4T1 mammary tumor model that shares many characteristics with human breast cancer, particularly its ability to spontaneously metastasize to the lungs, we demonstrate that Gr-1+CD11b+ cells or myeloid derived suppressor cells are important mediators in TGF-β regulation of mammary tumor progression. Depletion of Gr-1+CD11b+ cells diminished the antitumor effect of TGF-β neutralization. Two mechanisms were involved: first, treatment with TGF-β neutralization antibody (1D11) significantly decreased the number of Gr-1+CD11b+ cells in tumor tissues and premetastatic lung. This is mediated through increased Gr-1+CD11b+ cell apoptosis. In addition, 1D11 treatment significantly decreased the expression of Th2 cytokines and Arginase 1. Interestingly, the number and property of Gr-1+CD11b+ cells in peripheral blood/draining lymph nodes correlated with tumor size and metastases in response to 1D11 treatment. Our data suggest that the efficacy of TGF-β neutralization depends on the presence of Gr-1+CD11b+ cells, and these cells could be good biomarkers for TGF-β-targeted therapy.     

Sonography in identification of abdominal wall lesions presenting as palpable masses.

OBJECTIVE: Abdominal wall lesions often present as palpable masses. The purpose of this presentation is to provide an overview of the sonographic appearances of different abdominal wall lesions. METHODS: Patients were scanned with high-frequency (5- to 12-MHz) linear transducers. Extended or panoramic views were recorded often to show the lesion in perspective to adjacent structures in the abdominal wall. RESULTS: The different layers of the abdominal wall could be clearly shown on high-frequency sonography, and the abdominal wall abnormalities were recognized in all the patients. CONCLUSIONS: Hernias are the most common abdominal wall lesions. Herniated bowel loops have variable appearances depending on their air-fluid content and degree of obstruction. Localized fluid collections in the abdominal wall (seromas, liquefying hematomas, and abscesses) can be well visualized. More infrequently, tumors or vascular lesions can be identified in the abdominal wall.     

Hepatic perivascular mesenchymal stem cells with myogenic properties

Pericytes are multipotent mesenchymal stem cells located on the walls of blood vessels in various organs and are characterized as CD146⁺ cells. In this study, we first immunohistochemically detected pericytes in the perivascular regions of liver from two mouse genotypes, namely wild‐type (WT) and myostatin null (Mstn^?/?). We further isolated pericytes using sorting as CD146⁺ CD34^? CD56^? CD45^? cells. The main finding of this study involves the contrasting fibrogenic vs. myogenic behaviour of liver pericytes from WT and Mstn^?/? mice, respectively. Sorted CD146⁺ liver pericytes (WT and Mstn^?/?) expressed PDGFRβ, NG2, vimentin, adult stem cell markers CD73, CD105, CD44 and could be readily differentiated into adipogenic, osteogenic and chondrogenic lineages. Furthermore, these CD146⁺ cells from WT and Mstn^?/? livers did not express myostatin, in contrast to the total liver tissue of WT. The absence of αSMA and GFAP made these cells easily distinguishable from hepatic stellate cells. When subjected to standard myogenic differentiation with low serum the CD146⁺ cells from WT liver differentiated into myofibroblasts (fibrogenic) and the CD146⁺ cells from Mstn^?/? liver differentiated into multinucleated myotubes (myogenic). Finally, we transplanted CD146⁺ pericytes into tibialis anterior muscle of dystrophic mice and established the generation of novel myofibres, thereby proving their cell therapy potential. The liver tissue microenvironment with myostatin in WT and the absence of myostatin in Mstn^?/? conditions might exert a paracrine effect in determining the fate of pericyte‐like cells in the liver.     

Cost and efficacy of immunosuppression using generic products following living donor liver transplantation in India

Background  

Cost of post liver transplant immunosuppression is a major financial burden to patients in developing countries. In India, generic varieties of various immunosuppressants are often used without any definite evidence to their efficacy. This study was aimed at studying the dosage, side effect profile and cost of post-liver transplant immunosuppression using generic products in Indian population following living donor liver transplantation (LDLT).     

Clinical and Radiologic Outcome of Gamma Knife Radiosurgery on Nonfunctioning Pituitary Adenomas

Objective To elucidate the role of Gamma Knife radiosurgery (GKRS) in the management of nonfunctioning pituitary adenomas (NFAs). Materials and Methods A retrospective review of 57 consecutive patients spanning 2000 to 2013 with NFAs was performed. Of 57 patients, 53 patients had recurrent or residual tumors after microsurgical resection. The study population was evaluated clinically and radiographically after GKRS treatment. The median follow-up time was 45.57 months. Results GKRS in pituitary adenomas showed significant variations in tumor growth control (decreased in 32 patients [56.1%], arrested growth in 21 patients [36.1%], and increased tumor size in 4 patients [7%]). Progression-free survival after GKRS at 3, 7, and 10 years was 100%, 98%, and 90%, respectively. The neurologic signs and symptoms were significantly improved after GKRS (14% versus 107%) compared with pretreated signs and symptoms (p < 0.0001). Five patients (8.8%) required additional treatment. Conclusion Recent follow-up revealed that GKRS offers a high rate of tumor control and preservation of neurologic functions in both new and recurrent patients with NFAs. Thus GKRS is an effective treatment option for recurrent and residual as well as newly diagnosed patients with NFAs.     

Occipitocervical Fusion Surgery: Review of Operative Techniques and Results

Objective Varying types of clinicoradiologic presentations at the craniovertebral junction (CVJ) influence the decision process for occipitocervical fusion (OCF) surgery. We discuss the operative techniques and decision-making process in OCF surgery based on our clinical experience and a literature review. Material and Methods A total of 49 consecutive patients who underwent OCF participated in the study. Sagittal computed tomography images were used to illustrate and measure radiologic parameters. We measured Wackenheim clivus baseline (WCB), clivus-canal angle (CCA), atlantodental distance (ADD), and Powers ratio (PR) in all the patients. Results Clinical improvement on Nurick grading was recorded in 36 patients. Patients with better preoperative status (Nurick grades 1–3) had better functional outcomes after the surgery (p = 0.077). Restoration of WCB, CCA, ADD, and PR parameters following the surgery was noted in 39.2%, 34.6%, 77.4%, and 63.3% of the patients, respectively. Complications included deep wound infections (n = 2), pseudoarthrosis (n = 2), and deaths (n = 4). Conclusion Conventional wire-based constructs are superseded by more rigid screw-based designs. Odontoidectomy is associated with a high incidence of perioperative complications. The advent of newer implants and reduction techniques around the CVJ has obviated the need for this procedure in most patients.     

Johann Christian Rosenmüller (1771-1820): A Historical Perspective on the Man behind the Fossa

Introduction The fossa of Rosenmüller, also known as the lateral pharyngeal recess, is a well-established site of origin of nasopharyngeal carcinoma. It is located in the lateral pharyngeal wall behind the cartilaginous portion of the Eustachian tube, the torus tubarius, and is named after Johann Christian Rosenmüller (JCR).Objective We present a history on the life and extensive works of Johann Christian Rosenmüller, a German physician and anatomist.Results Johann Christian Rosenmüller was a dedicated anatomist. In addition to identifying the fossa of Rosenmüller, his influence extends to various other anatomic subjects, including the Rosenmüller gland, the palpebral portion of the lacrimal gland, and the organ of Rosenmüller (i.e., the caudal remnant of the mesonephric duct). He was also an avid speleologist, studying the composition of caves and their life forms. For his contributions to this field, he had a cave in Germany and an extinct species named after him—Rosenmüllerhöhle and Ursus spelaeus Rosenmüller, respectively.Conclusion The fossa of Rosenmüller plays an important role in the growth and surgical treatment of nasopharyngeal carcinoma. We present a brief glimpse into the life of Johann Christian Rosenmüller, for whom it was named.     

Long-Term Outcome of Gamma Knife Radiosurgery for Vestibular Schwannoma

Objective We evaluated the long-term outcome of vestibular schwannoma (VS) treated with gamma knife radiosurgery (GKRS) as a primary treatment as well as an adjunct therapy. Materials and Methods We performed a retrospective review (2000–2012) of 82 patients with VS who received GKRS. Of 82 patients, 20 patients with prior resection received GKRS treatment as an adjunct therapy. The remainder of the patients (62) received GKRS as a primary treatment. Results GKRS for VS showed significant variations in tumor growth control (decreased in 44 patients [54%], arrested growth in 30 patients [36%], and increased tumor size in 8 patients [10%]). Progression-free survival rates after GKRS at 3, 5, and 10 years were 98%, 95%, and 95%, respectively. Hearing, facial nerve function, and Karnofsky performance scale were significantly improved after GKRS compared with pretreated status (79 versus 90). Two patients (2.5%) required resection again due to tumor progression and worsening of signs and symptoms. Conclusion Long-term follow-up demonstrated that GKRS offers a high rate of tumor control, preservation of multiple nerve functions, and a good quality of life in both new and recurrent patients with VS.