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Fischer J.E.,Harvard University | Fischer J.E.,University of Cincinnati | Fischer J.E.,Beth Israel Deaconess Medical Center | Jones D.B.,Harvard University | And 9 more authors.
Fischer's Mastery of Surgery: Sixth Edition

The scope of Fischers Mastery of Surgery, Sixth Edition, is consistent with the broad training of a general surgeon, providing extensive coverage of vascular surgery as well as of common thoracic, breast, esophageal, endocrine, colorectal, gastric, pancreatic, liver, and biliary procedures. Each procedural chapter reviews the essentials of diagnosis, anatomy, and pre-operative planning, but focuses most heavily on step-by-step depictions and descriptions of procedures. Each chapter concludes, as is traditional for this classic text, with an editorial commentary which strives to put the chapter in a broad context and provide helpful critiques of the most recent literature. The sixth edition will include a dozen new chapters, including endovascular treatment of varicose veins, fasciotomy, and thoracic aortic transaction. The vascular section has been completely reorganized and will incorporate both open and endovascular procedures. For the first time, the sixth edition is in full color. © 2012 by LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER business. All rights reserved. Source

Suva L.J.,Winthrop P Rockefeller Cancer Institute | Washam C.,Winthrop P Rockefeller Cancer Institute | Nicholas R.W.,Winthrop P Rockefeller Cancer Institute | Griffin R.J.,University of Arkansas for Medical Sciences
Nature Reviews Endocrinology

The skeleton is one of the most common sites for metastatic cancer, and tumors arising from the breast or prostate possess an increased propensity to spread to this site. The growth of disseminated tumor cells in the skeleton requires tumor cells to inhabit the bone marrow, from which they stimulate local bone cell activity. Crosstalk between tumor cells and resident bone and bone marrow cells disrupts normal bone homeostasis, which leads to tumor growth in bone. The metastatic tumor cells have the ability to elicit responses that stimulate bone resorption, bone formation or both. The net result of these activities is profound skeletal destruction that can have dire consequences for patients. The molecular mechanisms that underlie these painful and often incurable consequences of tumor metastasis to bone are beginning to be recognized, and they represent promising new molecular targets for therapy. © 2011 Macmillan Publishers Limited. All rights reserved. Source

Batchu R.B.,Wayne State University | Batchu R.B.,John ngell Va Medical Center | Batchu R.B.,Virocan Therapeutics Pvt. Ltd | Gruzdyn O.V.,Wayne State University | And 11 more authors.

MAGE-A3 is highly expressed in epithelial ovarian cancer (EOC), making it a promising candidate for immunotherapy. We investigated whether dendritic cells (DCs) transduced with a rAAV-6 capsid mutant vector Y445F could elicit effective MAGE-A3-specific anti-tumor cytotoxic T lymphocyte (CTL) responses in vitro. MAGE-A3 was cloned and rAAV-6-MAGE-A3 purified, followed by proviral genome detection using real-time PCR. Immunofluorescence detection of rAAV-6-Y445F-MAGE-A3-transduced DCs demonstrated 60% transduction efficiency. Fluorescent in situ hybridization analysis confirmed chromosomal integration of rAAV vectors. Flow cytometric analysis of transduced DCs showed unaltered expression of critical monocyte-derived surface molecules with retention of allo-stimulatory activity. Co-culture of autologous T lymphocytes with MAGE-A3-expressing DCs produced CTLs that secreted IFN-γ, and efficiently killed MAGE-A3+ EOC cells. This form of rAAV-based DC immunotherapy, either alone or more likely in combination with other immune-enhancing protocols, may prove useful in the clinical setting for management of EOC. © 2013 Elsevier Ltd. Source

Johnson C.B.,University of Arkansas for Medical Sciences | Johnson C.B.,Winthrop P Rockefeller Cancer Institute | Boneti C.,University of Arkansas for Medical Sciences | Korourian S.,University of Arkansas for Medical Sciences | And 2 more authors.
Annals of Surgery

OBJECTIVE: Our objective is to prove that injection of technetium-99m (Tc99) sulfur colloid in a subareolar manner, after induction of anesthesia, is a safe and effective technique for sentinel lymph node identification in breast cancer patients. INTRODUCTION: Preoperative injection of Tc99 and lymphoscintigraphy is standardly performed before sentinel lymph node biopsy (SLNB) for breast cancer. Blue dye is often used to help guide and confirm the localization but tattoos the breast. This method is limited because of painful injections, variable identification rates, added costs and unnecessary scheduling delays. We hypothesized that intraoperative injection alone by the surgeon of dermal or subareolar Tc99 is practical for the identification of sentinel lymph node in breast cancer. METHODS: This is a prospective single institution study that was approved by our institutional review board. All patients with operable breast cancer that were eligible for a SLNB from October 2002 to October 2010 were included in our study population. After induction and before sterile preparation of the operative field 1 mCi of Tc-99 unfiltered was administered by a subareolar injection. In patients where the scar was in the periareolar region or in the upper outer quadrant a dermal injection using 0.25mCi was used. Confirmatory Lymphazurin was also injected early on in this series but became unnecessary later in the study. Site and type of injection, injection time, incision time, and extraction time along with other factors for the purposes of the study were recorded. Data comparing injection preoperative and intraoperative were collected. RESULTS: Six hundred ninty-nine patients were accrued for a SLNB with an average age 57.1 ± 12.8 (range 24-92). Seventy-six patients underwent 2 SLNB procedures for a total of 775 intraoperative Tc-99 injections. Six patients underwent intraoperative dermal injection with Tc-99. The average dose of Tc-99 administered was 1.157 ± 0.230 mCi. The sentinel node was localized in 98.6% of the cases (419/425) of subareolar radiotracer alone, 94.8% (326/344) in dual injection and 100% (6/6) in dermal injection. Average time from injection to incision was 41.20 ± 29.56 minutes for radiotracer injection in subareolar region only. For dermal injections it was 40.83 ± 39.64 minutes. For patients with dual injection of Lymphazurin and radiotracer it was 31.74 ± 24.86 minutes. The average ex vivo count was 6474 ± 8395 for dermal injection, 28,250 ± 69,932 for Tc-99 subareolar injection, and 35,501 ± 97,753 for dual subareolar injection. Intraoperative radiotracer alone incurred a charge of $189.00; Lymphazurin blue dye added $591.40, whereas preoperative injection had a charge of $1257.06 associated with imaging, injection, and interpretation of images. CONCLUSION: Intraoperative injection of Tc99 alone with a subareolar or dermal injection technique rapidly localizes the sentinel node in breast cancer, is an oncologically sound procedure, is cost effective and facilitates operative room time management. Copyright © 2011 by Lippincott Williams & Wilkins. Source

Ramani V.C.,University of Arkansas for Medical Sciences | Kaushal G.P.,University of Arkansas for Medical Sciences | Haun R.S.,University of Arkansas for Medical Sciences | Haun R.S.,Winthrop P Rockefeller Cancer Institute
Biochimica et Biophysica Acta - Molecular Cell Research

The gelatinases, matrix metalloproteinase (MMP)-9 and -2, are produced as latent, inactive enzymes that can be proteolytically activated by a number of proteases. In many normal and pathological conditions, where the expression of MMPs is deregulated, changes in the expression of other proteases have also been reported. Human kallikrein-related peptidase 7 (KLK7), a chymotryptic-like serine protease, is overexpressed in many different types of neoplastic conditions, which have also been shown to express high levels of both MMP-9 and -2. Since the activation of MMPs by KLK7 has never been examined, we sought to determine whether KLK7 can activate these MMPs. To test this hypothesis KLK7 was incubated with the recombinant MMPs and the products of the reaction were analyzed for their activity. Incubation of proMMP-9 with KLK7 resulted in the production of a novel truncated, active MMP-9 lacking the C-terminal hemopexin domains. In contrast, KLK7 degraded, but did not activate, proMMP-2. The novel activation of proMMP-9 by KLK7 was further confirmed using conditioned medium prepared from an MMP-9-expressing cell line, MDA-MMP-9. Our results clearly establish that KLK7 activates proMMP-9 to produce a novel truncated, active MMP-9 product not generated by other proteases. These findings suggest that KLK7 may play an important role in the activation of MMP-9 in tumors that express high levels of both these proteases and the resulting truncated MMP may possess altered substrate specificities compared with full-length MMP-9 activated by other proteases. © 2011 Elsevier B.V. Source

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