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Purpose Bone Morphogenetic Protein-2 (BMP-2) may offer the potential to enhance allograft-host osseous union in limb-salvage surgery following osteosarcoma resection. However, there is concern regarding the effect of locally applied BMP-2 on tumor recurrence and metastasis. The purpose of this project was to evaluate the effect of exogenous BMP-2 on osteosarcoma migration and invasion across a panel of tumor cell lines in vitro and to characterize the effect of BMP-2 on pulmonary osteosarcoma metastasis within a xenograft model. Experimental design The effect of BMP-2 on in vitro tumor growth and development was assessed across multiple standard and patient-derived xenograft osteosarcoma cell lines. Tumor migration capacity, invasion, and cell proliferation were characterized. In addition, the effect on metastasis was measured using a xenograft model following tail-vein injection. The effect of exogenous BMP-2 on the development of metastases was measured following both single and multiple BMP-2 administrations. Results There was no significant difference in migration capacity, invasion, or cell proliferation between the BMP-2 treated and the untreated osteosarcoma cell lines. There was no significant difference in pulmonary metastases between either the single-dose or multi-dose BMP-2 treated animals and the untreated control animals. Conclusions In the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs.

INTRODUCTION The vascularized fibular graft prosthetic composite (VFGPC) is used for reconstruction after internal hemipelvectomy. The purpose of this study was to create a mathematical model that calculates the mechanical effects of the vascularized fibular graft on the VFGPC. METHODS The effects of the VFG positioning were calculated based on three-dimensional static analyzes to determine the direction, magnitude, and distribution of the forces through the prosthesis and VFG. The shear stress (SS) and cyclic loads to failure (CLF) were calculated. By varying the location of the VFG on the sacrum the zone of acceptable placement was calculated. RESULTS Utilization of the VFG decreased the forces through the implant by 15-35% and decreased SS 20-54%, depending on stance. The CLF improved by 94%. The zone of acceptable placement for the VFG was found to be between 0° and 15° of the vertical axis in the sagittal plane and 0° and 30° of the posterior axis in coronal plane. CONCLUSION Determining the position of the VFG pre-operatively allows for the creation of a customized cutting jig can be utilized to create graft allowing for accurate fibular osteotomies, minimization of ischemia time, and decreased intra-operative handling of the graft.

Over the past four decades there have been minimal improvements in outcomes for patients with osteosarcoma. New targets and novel therapies are needed to improve outcomes for these patients. We sought to evaluate the prevalence and clinical significance of the newest immune checkpoint, HHLA2, in osteosarcoma. HHLA2 protein expression was evaluated in primary tumor specimens and metastatic disease using an osteosarcoma tumor microarray (TMA) (n = 62). The association of HHLA2 with the presence of tumor infiltrating lymphocytes (TILs) and five-year-event-free-survival were examined. HHLA2 was expressed in 68% of osteosarcoma tumors. HHLA2 was expressed in almost all metastatic disease specimens and was more prevalent than in primary specimens without known metastases (93% vs 53%, p = 0.02). TILs were present in 75% of all osteosarcoma specimens. Patients whose tumors were ≥25% or ≥50% HHLA2 positive had significantly worse five-year event-free-survival (33% vs 64%, p = 0.03 and 14% vs 59%, p = 0.02). Overall, we have shown that HHLA2 is expressed in the majority of osteosarcoma tumors and its expression is associated with metastatic disease and poorer survival. Along with previously reported findings that HHLA2 is a T cell co-inhibitor, these results suggest that HHLA2 may be a novel immunosuppressive mechanism within the osteosarcoma tumor microenvironment.

Osteosarcoma patient survival has remained stagnant for 30 years. Novel therapeutic approaches are needed to improve outcomes. We examined the expression of Programmed Death Ligand 1 (PD-L1) and defined the tumor immune microenvironment to assess the prognostic utility in osteosarcoma. PD-L1 expression in osteosarcoma was examined in two patient cohorts using immunohistochemistry (IHC) (n = 48, n = 59) and expression was validated using quantitative real time PCR (n = 21) and western blotting (n = 9). IHC was used to determine the presence of tumor infiltrating lymphocytes and antigen-presenting cells (APCs) in the tumor. Expression of PD-L1 was correlated with immune cell infiltration and event-free-survival (EFS). The 25% of primary osteosarcoma tumors that express PD-L1 were more likely to contain cells that express PD-1 than PD-L1 negative tumors (91.7% vs 47.2%, p = 0.002). Expression of PD-L1 was significantly associated with the presence of T cells, dendritic cells, and natural killer cells. Although all immune cell types examined were present in osteosarcoma samples, only infiltration by dendritic cells (28.3% vs. 83.9%, p = 0.001) and macrophages (45.5% vs. 84.4%, p = 0.031) were associated with worse five-year-EFS. PD-L1 expression was significantly associated with poorer five-year-EFS (25.0%. vs. 69.4%, p = 0.014). Further studies in osteosarcoma are needed to determine if targeting the PD-L1:PD-1 axis improves survival.

Patients with relapsed and refractory solid tumors have a poor prognosis. Recent advances in genomic technology have made it feasible to screen tumors for actionable mutations, with the anticipation that this may provide benefit to patients. Pediatric oncologists were emailed an anonymous 34-question survey assessing their willingness to offer a rebiopsy to patients with relapsed disease for the purpose of tumor genomic profiling. They were presented with two scenarios evaluating morbidity and invasiveness of the procedures using the clinical examples of medulloblastoma and Ewing sarcoma. A total of 195 pediatric oncologists responded to the questionnaire. Morbidity and invasiveness of the procedure demonstrated significant differences in provider willingness to refer their patients for rebiopsy. The pretest probability was a major variable influencing provider willingness to offer a rebiopsy. Respondents were more likely to offer a rebiopsy if the likelihood was high that the results would have an impact on clinical management than if the biopsy was for histologic confirmation alone (mean 89 vs. 56 %; p = 0.017). Compared with the rate of a rebiopsy for histologic confirmation, significantly fewer providers were willing to offer a rebiopsy if they were led to believe the likelihood of finding an actionable mutation was low (mean 45 vs. 56 %; p = 0.021). The scenario showed that the pretest probability of finding an actionable mutation was influential in determining provider willingness to offer a rebiopsy for the purpose of tumor genomic profiling. Further research is warranted to evaluate the benefit of tumor genomic profiling in terms of patient outcomes.

Aim: To examine the effects of flavokawain B (FKB), a novel kava chalcone, on the growth of uterine leiomyosarcoma (LMS) cells and investigated its utility in the treatment of uterine LMS. Material and Methods: Uterine leiomyosarcoma (SK-LMS-1), endometrial adenocarcinoma (ECC-1) and the non-malignant, human endometrium fibroblast-like (T-HESC) cell lines were cultured and treated with different concentrations of FKB. Cell viability was determined by MTT assays and the IC50 was estimated. Fluorescent-activated cell sorting (FACS) analysis of apoptosis and cell cycle was performed. Real-time reverse-transcription polymerase chain reaction and western blot analysis were utilized to evaluate differences in the expression of apoptotic markers. Results: FKB preferentially inhibited the growth of SK-LMS-1 and ECC-1 cells compared to T-HESC control cells. FKB significantly increased both early and late apoptosis in SK-LMS-1 and ECC-1 cells relative to control. Cell cycle analysis illustrated an increase in the G2/M fraction in treated cell lines relative to control. Furthermore, FKB induced the expression of pro-apoptotic death receptor 5 (DR5), Bim, and Puma, and decreased expression of an inhibitor of apoptosis, survivin. FKB also acted synergistically when combined with docetaxel and gemcitabine (combination index = 0.260). Conclusion: FKB treatment results in cell cycle arrest and a robust induction of apoptosis in SK-LMS-1 and ECC-1 cell lines. This natural product deserved further investigation as a potential therapeutic agent in the treatment of uterine LMS.

Background: Chordoma is the most common primary malignant tumor of the spine. It is extremely rare and has been studied primarily in single-institution case series. Using data from a large, population-based cancer registry, we designed the present study to examine the outcome for patients with chordoma and to determine relevant prognostic factors. Methods: A retrospective analysis of the California Cancer Registry database was performed to identify patients with a diagnosis of chordoma in the years 1989 to 2007. Comparisons examined differences in demographics, disease characteristics, treatment, and survival. Survival analyses were performed with use of the Kaplan-Meier method with log-rank tests and Cox proportional hazards models. Results: Four hundred and nine patients with chordoma were identified; 257 (62.8%) were male and 152 (37.2%) were female. With regard to racial or ethnic distribution, 266 patients (65%) were white; ninety-three (22.7%), Hispanic; forty-three (10.5%), Asian or other; and seven (1.7%), black. The site of presentation was the head in 202 patients (49.4%), spine in 106 patients (25.9%), and pelvis and/or sacrum in 101 patients (24.7%). Hispanic race (p = 0.0002), younger age (less than forty years; p < 0.0001), and female sex (p = 0.009) were associated with cranial presentation, whereas older age (forty years or older; p < 0.0001) was associated with pelvic presentation. After adjustment for clinically relevant factors, a significantly decreased risk of death for chordoma-specific survival was seen for Hispanic race (hazard ratio = 0.51, 95% confidence interval [95% CI], 0.28 to 0.93; p = 0.03), high socioeconomic status (hazard ratio = 0.8, 95% CI, 0.67 to 0.95; p = 0.01), and local excision and/or debulking (hazard ratio = 0.38, 95% CI, 0.18 to 0.81; p = 0.01). Large tumor size was independently associated with an increased risk of death (hazard ratio = 2.05, 95% CI, 1.01 to 4.20; p = 0.048). Conclusions: In this study, the survival of patients with chordoma was significantly better for those who were Hispanic and had a small tumor, high socioeconomic status, and surgical intervention. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Our on-going mixed-methods study examines the relationship between wisdom and other variables such as religiosity, spirituality, and quality of life among 75 Canadians and 89 South Koreans (total 164) in two age groups: 106 younger adults [age 18–25], and 58 older adults [age 60–85]). Multiple regression and bivariate correlation analyses reveal that these variables predict wisdom in both age groups, although quality of life is the only significant variable to predict wisdom in both groups. Only quality of life is correlated to the total wisdom score in the younger groups, whereas quality of life, religious experience, and spirituality are positively related to wisdom in the older age groups. Interestingly though, the elders’ daily spiritual experience is negatively related to wisdom. The results show that elders in both countries who seek spirituality, religious experience and belief are more likely wise, and their wisdom may link to their quality of life.

Synovial sarcomas (SS) are soft tissue sarcomas with poor prognosis, displaying a lack of response to conventional cytotoxic chemotherapy. Although SS cell lines have moderate chemosensitivity to isofamide and doxorubicin therapy, the clinical prognosis is still poor. In this article, we showed that flavokawain B (FKB), a novel chalcone from kava extract, potently inhibits the growth of SS cell lines SYO-I and HS-SY-II through induction of apoptosis. Treatment with FKB increased caspase 8, 9, and 3/7 activity compared to vehicle-treated controls, indicating that both extrinsic and intrinsic apoptotic pathways were activated. Furthermore, FKB treatment of both cell lines resulted in increased mRNA and protein expression of death receptor-5 and the mitochondrial pro-apoptotic proteins Bim and Puma, while down-regulating the expression of an inhibitor of apoptosis, survivin in a dose-dependent manner. Our results suggest the natural compound FKB has a pro-apoptotic effect on SS cell lines. FKB may be a new chemotherapeutic strategy for patients with SS and deserves further investigation as a potential agent in the treatment of this malignancy.

Osteosarcoma is the most common primary bone malignancy, with a high propensity for local invasion, early metastasis and relapse. While the molecular mechanisms behind osteosarcoma development and metastasis have not yet been fully elucidated, research has highlighted an important role for Wnt signaling. Several Wnt ligands, receptors and coreceptors are highly expressed in osteosarcoma cell lines, while Wnt inhibitors are downregulated. As a result, research has begun to identify mechanisms with which to inhibit Wnt signaling. The use of Wnt pathway inhibitors and the targeting of c-Met, a Wnt regulated proto-oncogene, may be two possible mechanisms for treatment of osteosarcoma. In addition, as the Wnt signaling pathway is a regulator of stem cells, reagents that function as Wnt inhibitors are currently under investigation as inhibitors of cancer stem cell proliferation. Research involving the Wnt signaling pathway and cancer stem cells holds promise for novel treatment options in the future.

For this technology overview, the tools of evidence-based medicine were used to summarize information on the effectiveness and clinical outcomes related to the usage of bone void fillers- specifically, synthetic graft materials. Comprehensive literature searches were conducted to address five key questions, which the task force that prepared the report posed as follows. Question 1 addressed the use of synthetic bone void fillers alone. Question 2 was designed to determine whether synthetic bone void fillers could successfully serve as graft extenders and eliminate the need for iliac crest bone graft. Questions 3, 4, and 5 addressed the use of allografts as a comparison with synthetic fillers because clinical results with allografts are perceived as being much closer to autografts in these areas of the spine.

Flavokawain B, a chalcone isolated from kava root extracts, has been shown to inhibit the in vitro and in vivo growth of various cancer cell lines via induction of apoptosis. However, the mechanism of flavokawain B's action remains largely unknown. Here we have demonstrated that flavokawain B caused Skp2 degradation in an ubiquitin and proteasome dependent manner. In addition, flavokawain B inhibited NEDD8 conjugations to both Cullin1 and Ubc12 in PC3 cells and Ubc12 NEDDylation in an in vitro assay. Overexpression of dominant-negative cullin1 (1-452) or K720R mutant cullin1 rescued the effect of flavokawain B on Skp2 degradation, but further increased the expression of p27. However, siRNA knock-down of Skp1, CSN5, and UBC12 expression resulted in down-regulation of Skp2 expression and further enhanced the effect of flavokawain B on Skp2 degradation. siRNA knock-down of Cdh1, a known E3 ligase of Skp2 for targeted degradation, also didn't rescue the effect of flavokawain B on Skp2 degradation, but overexpression of F-box deleted Skp2 can reverse the effect of flavokawain B on Skp2 degradation. These results suggest that degradation of Skp2 by flavokawain B is involved in Cullin1. Furthermore, flavokawain B selectively inhibited the growth of pRb deficient cell lines and PC3 cells with Skp2 overexpression. Flavokawain B also acts synergistically with Bortezomib and MG132 to inhibit the growth of prostate cancer cell lines via down-regulation of Skp2 and up-regulation of p27 and p21 expression. These finding provide rationale for combination of flavokawain B and Bortezomib in treatment of prostate cancer. Citation Format: Xuesen Li, Victor Pham, Matthew Tippin, Shan Xu, Dongjun Fu, Liankun Song, Bang H. Hoang, Xiaolin Zi. Flavokawain B, a kava chalcone, acts synergistically with proteasome inhibitors (i.e., bortezomib and MG132) to reduce the growth of prostate cancer cells via downregulation of Skp2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 275.

Colorectal cancer (CRC) screening rates are lower in Vietnamese Americans than in non-Hispanic Whites. Most Vietnamese Americans have ethnically concordant physicians and are willing to have CRC screening if their physicians recommend it. We conducted two continuing medical education (CME) seminars with participants recruited from the Vietnamese Physician Association of Northern California to increase their CRC screening knowledge. We used pre- and post-CME surveys to evaluate the CMEs and per-item McNemar's tests to assess changes in knowledge. Correct responses increased significantly from pre- to post-CME for all five items on CRC burden and four of 11 items on screening guidelines and practices at the first CME and for five of seven items on screening guidelines and practices at the second CME. Continuing medical education seminars were effective in increasing CRC screening knowledge among Vietnamese American physicians. This increase may lead to physicians' recommending and their patients' completing CRC screening tests.

It has been reported that the progression of osteosarcoma was closely associated with the aberrant activation of canonical Wnt signaling. Wnt inhibitory factor-1 (WIF-1) is a secreted Wnt inhibitor whose role in human osteosarcoma remains unknown. In this study, WIF-1 expression in NHOst and osteosarcoma cell lines was determined by real-time reverse transcription-PCR, methylation-specific PCR, and Western blotting analysis. In addition, tissue array from patient samples was examined for WIF-1 expression by immunohistochemistry. Compared with normal human osteoblasts, WIF-1 mRNA and protein levels were significantly downregulated in several osteosarcoma cell lines. The downregulation of WIF-1 mRNA expression is associated with its promoter hypermethylation in these tested cell lines. Importantly, WIF-1 expression was also downregulated in 76% of examined osteosarcoma cases. These results suggest that the downregulation of WIF-1 expression plays a role in osteosarcoma progression. To further study the potential tumor suppressor function of WIF-1 in osteosarcoma, we established stable 143B cell lines overexpressing WIF-1. WIF-1 overexpression significantly decreased tumor growth rate in nude mice as examined by the s.c. injection of 143B cells stably transfected with WIF-1 and vector control. WIF-1 overexpression also markedly reduced the number of lung metastasis in vivo in an orthotopic mouse model of osteosarcoma. Together, these data suggest that WIF-1 exerts potent antiosteosarcoma effect in vivo in mouse models. Therefore, the reexpression of WIF-1 in WIF-1–deficient osteosarcoma represents a potential novel treatment and preventive strategy. Mol Cancer Ther; 9(3); 731–41

Diffuse optical spectroscopic imaging (DOSI) is an emerging near-infrared imaging technique that noninvasively measures quantitative functional information in thick tissue. This study aimed to assess the feasibility of using DOSI to measure optical contrast from bone sarcomas. These tumors are rare and pose technical and practical challenges for DOSI measurements due to the varied anatomic locations and tissue depths of presentation. Six subjects were enrolled in the study. One subject was unable to be measured due to tissue contact sensitivity. For the five remaining subjects, the signal-to-noise ratio, imaging depth, optical properties, and quantitative tissue concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipids from tumor and contralateral normal tissues were assessed. Statistical differences between tumor and contralateral normal tissue were found in chromophore concentrations and optical properties for four subjects. Low signal-to-noise was encountered during several subject's measurements, suggesting increased detector sensitivity will help to optimize DOSI for this patient population going forward. This study demonstrates that DOSI is capable of measuring optical properties and obtaining functional information in bone sarcomas. In the future, DOSI may provide a means to stratify treatment groups and monitor chemotherapy response for this disease.

In the present study, in vitro and in vivo studies were conducted to determine the relationship between innate substance P (SP) levels and alcohol-motivated behavior in alcohol-preferring (P) and nonpreferring (NP) rat lines. In Experiment 1, in situ hybridization and quantitative autoradiography were used to detect and measure SP mRNA levels in discrete brain loci of the P and NP rats. The results indicated significantly lower SP mRNA levels in the central nucleus of the amygdala (CeA) of P compared with those of NP rats. Experiment 2 evaluated the effects of SP, microinfused into the CeA, on alcohol (10%, v/v) and sucrose (2%, w/v) motivated responding in the P rat. The results revealed that, when infused into the CeA (1–8 μg), SP reduced alcohol responding by 48–85% of control levels, with no effects on sucrose responding. Neuroanatomical control infusions (1–8 μg) into the caudate putamen (CPu) also failed to significantly alter alcohol- or sucrose-motivated behaviors. Given the selective reductions on alcohol (compared to sucrose) responding by direct intracranial infusion of SP, the data suggest that deficits in SP signaling within the CeA (an anxiety regulating locus) are inversely associated with alcohol-motivated behaviors. Activation of SP receptors in the CeA may reduce anxiety-like behavior in the P rat and contribute to reductions on alcohol responding. The SP system may be a suitable target for the development of drugs to reduce alcohol-drinking behavior in humans. Synapse 63:972–981, 2009. © 2009 Wiley-Liss, Inc.

The John J. Fahey, MD, Memorial North American Traveling Fellowship (NATF) originated in 1968 at an American Orthopaedic Association (AOA) Executive Committee meeting. In 1969, the committee's proposal to create a fellowship program for orthopaedic surgeons to travel to orthopaedic centers around the United States and Canada was accepted. The tour's purpose is to promote clinical and scientific exchange and fellowship at each orthopaedic program visited. The 2007 tour was organized by Sohail Mirza, MD (University of Washington), and was coordinated by Lesley Coussis of the AOA office and Trinity Wittman of the Canadian Orthopaedic Association. The 2007 fellows, who hailed from diverse areas and orthopaedic specialties, were George Athwal, a shoulder and elbow surgeon from London, Ontario, Canada (University of Western Ontario); Bang Hoang, a musculoskeletal oncologist from Irvine, California (University of California, Irvine); Samir Mehta, a trauma surgeon from Philadelphia, Pennsylvania (University of Pennsylvania); Brett Owens, a sports medicine surgeon from El Paso, Texas (William Beaumont Army Medical Center); and Jennifer Wolf, a hand and elbow surgeon from Denver, Colorado (University of Colorado Health Sciences Center). We began our tour in Charlotte, North Carolina, where we were hosted by Edward Hanley Jr., MD, and Steven Frick, MD, of the Carolinas Medical Center. On October 1, 2007, the inaugural day of the North American Traveling Fellowship, the Department of Orthopaedics hosted an academic program in the morning. Later that day, the fellows had the opportunity to spend time with Dr. Hanley, who gave us many pearls of wisdom, including his philosophy of leadership and management as a chairman. The next day, each fellow spent the morning with members in their specific specialty, followed by a trip to the U.S. National Whitewater Center in Charlotte, where we had a thrilling few rides on the manmade training center's river, complete with …

Purpose: Two major systems exist for folate cell entry: the reduced folate carrier (RFC) and the folate receptor (FR). Although defective RFC-mediated transport was frequently identified as a mechanism of methotrexate (MTX) resistance in osteosarcoma, the status of FR and its role in this disease are unknown. Experimental Design: mRNA for FRα was measured in 107 osteosarcoma specimens using quantitative reverse transcription-PCR and was related to RFC expression. The effect of FRα overexpression on MTX resistance and natural folate uptake was studied using FRα non-expressing osteosarcoma 143B cells transfected with FRα cDNA in comparison with those transfected with sense or antisense RFC in the same genetic background. Results: Eighty-four samples (78.5%) had detectable FRα mRNA, and 29.9% had higher levels than the ovarian cancer cell line SKOV-3. No correlation was found between mRNA levels of FRα and RFC (r2 = 0.002). FRα overexpression had minor effects on the transport of MTX and sensitivity to this drug. Among the transfected 143B sublines, only the 143B-FRα was able to uptake 5-methyltetrahydrofolate when the extracellular concentration was reduced to 2 nmol/L, which conferred a growth advantage in physiologic folate concentrations compared with vector-only–transfected cells. Importantly, this was not similarly achieved by RFC overexpression. Conclusions: This study suggests that FRα plays a role in the uptake of 5-methyltetrahydrofolate when the concentration gradient is insufficient for RFC-mediated transport. FRα overexpression is unlikely secondary to the decreased RFC expression in osteosarcoma.

Osteosarcoma is the most common primary bone malignancy in children and is associated with rapid bone growth. Parathyroid hormone-related peptide (PTHrP) signaling via parathyroid hormone Type 1 receptor (PTHR1) is important for skeletal development and is involved in bone metastases in other tumors. The aim of this study was to investigate the status of PTHrP/PTHR1 and its possible role in osteosarcoma. In a preliminary screening, a higher level of PTHR1 mRNA, but not PTHrP, was found in 4 osteosarcoma xenografts as compared with 4 standard cell lines, or 5 patient derived cell lines (p < 0.05) using quantitative RT-PCR. It was therefore extended to 55 patient specimens, in which a significantly higher level of PTHR1 mRNA was detected in metastatic or relapsed samples than those from primary sites (p < 0.01). Cell behavior caused by PTHR1 overexpression was further studied in vitro using PTHR1 transfected HOS cell line as a model. Over-expression of PHTR1 resulted in increased proliferation, motility and Matrigel invasion without addition of exogenous PTHrP suggesting an autocrine effect. Importantly, the aggressiveness in PTHR1-expressing cells was completely reversed by RNAi mediated gene knockdown. In addition, PTHR1 over-expression led to delayed osteoblastic differentiation and upregulation of genes involved in extracellular matrix production, such as TGF-β1 and connective tissue growth factor. When cocultured with bone marrow derived monocytes, PTHR1 transfected HOS cells induced a greater number of osteoclasts. This study suggests that PTHR1 over-expression may promote osteosarcoma progression by conferring a more aggressive phenotype, and forming a more favorable microenvironment. © 2007 Wiley-Liss, Inc.

Based largely on a number of short-term administration studies, growing evidence suggests that central oxytocin is important in the regulation of energy balance. The goal of the current work is to determine whether long-term third ventricular (3V) infusion of oxytocin into the central nervous system (CNS) is effective for obesity prevention and/or treatment in rat models. We found that chronic 3V oxytocin infusion between 21 and 26 days by osmotic minipumps both reduced weight gain associated with the progression of high-fat diet (HFD)-induced obesity and elicited a sustained reduction of fat mass with no decrease of lean mass in rats with established diet-induced obesity. We further demonstrated that these chronic oxytocin effects result from 1) maintenance of energy expenditure at preintervention levels despite ongoing weight loss, 2) a reduction in respiratory quotient, consistent with increased fat oxidation, and 3) an enhanced satiety response to cholecystokinin-8 and associated decrease of meal size. These weight-reducing effects persisted for approximately 10 days after termination of 3V oxytocin administration and occurred independently of whether sucrose was added to the HFD. We conclude that long-term 3V administration of oxytocin to rats can both prevent and treat diet-induced obesity.

The purpose of this study was to better understand if a health educational presentation using culturally adapted materials was understandable and culturally appropriate, and that the content was retained, in an older Vietnamese American population. This study used cognitive interviewing. A convenient sampling was used to recruit eight participants by staff of a community-based organization from its client base. This is the first study to document that family eating style poses a challenge for estimating food intake among Vietnamese Americans. Participants who ate in a family eating style were not able to recall or estimate the number of servings of protein and vegetables. Some older Vietnamese Americans used food for healing and self-adjusted portion sizes from dietary recommendations. Cognitive interviewing is a useful method to improve comprehension, retention, and cultural appropriateness of health educational materials. Further nutrition research concerning intake measurement in ethnic groups that practice a family eating style is warranted.

Current therapy for osteosarcoma successfully treats 60% to 70% of patients. Attempts to identify patients who will respond poorly to therapy has focused on the use of new biologic markers or microarray cluster analysis. New potential therapeutic targets, including growth factors, chemokines, transcription factors, and angiogenic factors, are being evaluated for their roles in osteosarcoma. These new targets may provide mechanisms to treat the patients who would respond poorly to standard therapy.