Adjuvant chemo-radiotherapy in patients with gastric cancer

Background: The role of adjuvant therapy in gastric cancer has been controversial. Aim : In this study, we report our experience with adjuvant chemotherapy and radiotherapy in patients with non-metastatic gastric cancer. Settings and Design : Fifty patients were reviewed and assigned to three therapeutic groups. Materials and methods: Twenty patients received radiotherapy with concomitant administration of 5-fluorouracil and leucovorin on the first and last three days of radiotherapy; 20 patients received a five-day cycle 5-fluorouracil and leucovorin followed four to five weeks later by radiotherapy concomitant with the administration of fluorouracil on the first and the last three days of radiotherapy. Four weeks after radiotherapy two more five-day cycles of chemotherapy were administered; 10 patients received three cycles of cisplatin/docetaxel followed by radiotherapy and three additional cycles of chemotherapy after the completion of radiotherapy. Statistical Analysis : Patients were evaluated for treatment-related toxicity, local recurrences, distant metastases and deaths. We also aimed to make any possible comparisons between different chemo-radiation protocols. Results : Within a median follow-up of 21,5 months seven patients developed local recurrence and 17 patients developed distant metastases. The overall death proportion was 42% (95% CI 28.2-56.8%). Despite the limited number of patients, no statistically significant differences in local recurrences, distant metastases and deaths were observed between the three protocols. Acute and long-term treatment-related toxicity was low and no treatment-related deaths were observed. Conclusion: Despite variations of chemotherapy, our study demonstrated that combined chemo-radiotherapy for patients with resected gastric cancer can be administered safely, with acceptable toxicity

Gliosarcoma: a study of four cases

Gliosarcomas (GS) are highly malignant and rare tumors of the central nervous system with a poor prognosis. We report here on four patients with GS, the median survival for whom was 9.25 months. Prognosis of GS remains poor, and a multidisciplinary approach (surgery, radiation therapy, and chemotherapy) seems to be associated with slightly more prolonged survival times

Elevated levels of numerous cytokines in drainage fluid after primary total hip arthroplasty

As cytokines are involved in wound healing and other inflammatory processes, it could be valuable to measure their levels at the operative site. This study was conducted to investigate whether different cytokines are measurable in drainage fluid and, when measurable, whether we can find a difference in cytokine levels between one and six hours postoperatively. Samples from the drainage system in 30 consecutive patients undergoing primary total hip replacement were collected at one and six hours after closure of the wound. Levels of several cytokines were measured in the drainage fluids. A significant elevation of almost all cytokines was observed between the sample after one hour and six hours postoperatively. We found a strong correlation between the different pro-inflammatory cytokines. The IL-6 to IL-10 ratio were also raised, showing a pro-inflammatory predominance. Levels were much higher than those previously shown in serum

Myoblast sensitivity and fibroblast insensitivity to osteogenic conversion by BMP-2 correlates with the expression of Bmpr-1a

<p>Abstract</p> <p>Background</p> <p>Osteoblasts are considered to primarily arise from osseous progenitors within the periosteum or bone marrow. We have speculated that cells from local soft tissues may also take on an osteogenic phenotype. Myoblasts are known to adopt a bone gene program upon treatment with the osteogenic bone morphogenetic proteins (BMP-2,-4,-6,-7,-9), but their osteogenic capacity relative to other progenitor types is unclear. We further hypothesized that the sensitivity of cells to BMP-2 would correlate with BMP receptor expression.</p> <p>Methods</p> <p>We directly compared the BMP-2 sensitivity of myoblastic murine cell lines and primary cells with osteoprogenitors from osseous tissues and fibroblasts. Fibroblasts forced to undergo myogenic conversion by transduction with a MyoD-expressing lentiviral vector (LV-MyoD) were also examined. Outcome measures included alkaline phosphatase expression, matrix mineralization, and expression of osteogenic genes <it>(alkaline phosphatase, osteocalcin </it>and <it>bone morphogenetic protein receptor-1A) </it>as measured by quantitative PCR.</p> <p>Results</p> <p>BMP-2 induced a rapid and robust osteogenic response in myoblasts and osteoprogenitors, but not in fibroblasts. Myoblasts and osteoprogenitors grown in osteogenic media rapidly upregulated <it>Bmpr-1a </it>expression. Chronic BMP-2 treatment resulted in peak <it>Bmpr-1a </it>expression at day 6 before declining, suggestive of a negative feedback mechanism. In contrast, fibroblasts expressed low levels of <it>Bmpr-1a </it>that was only weakly up-regulated by BMP-2 treatment. Bioinformatics analysis confirmed the presence of myogenic responsive elements in the proximal promoter region of human and murine <it>BMPR-1A/Bmpr-1a</it>. Forced myogenic gene expression in fibroblasts was associated with a significant increase in <it>Bmpr-1a </it>expression and a synergistic increase in the osteogenic response to BMP-2.</p> <p>Conclusion</p> <p>These data demonstrate the osteogenic sensitivity of muscle progenitors and provide a mechanistic insight into the variable response of different cell lineages to BMP-2.</p

Clinical characteristics and prognosis of osteosarcoma in young children: a retrospective series of 15 cases

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma is the most common primary bone malignancy in childhood and adolescence. However, it is very rare in children under 5 years of age. Although studies in young children are limited in number, they all underline the high rate of amputation in this population, with conflicting results being recently reported regarding their prognosis.</p> <p>Methods</p> <p>To enhance knowledge on the clinical characteristics and prognosis of osteosarcoma in young children, we reviewed the medical records and histology of all children diagnosed with osteosarcoma before the age of five years and treated in SFCE (Société Française des Cancers et leucémies de l'Enfant) centers between 1980 and 2007.</p> <p>Results</p> <p>Fifteen patients from 7 centers were studied. Long bones were involved in 14 cases. Metastases were present at diagnosis in 40% of cases. The histologic type was osteoblastic in 74% of cases. Two patients had a relevant history. One child developed a second malignancy 13 years after osteosarcoma diagnosis.</p> <p>Thirteen children received preoperative chemotherapy including high-dose methotrexate, but only 36% had a good histologic response. Chemotherapy was well tolerated, apart from a case of severe late convulsive encephalopathy in a one-year-old infant. Limb salvage surgery was performed in six cases, with frequent mechanical and infectious complications and variable functional outcomes.</p> <p>Complete remission was obtained in 12 children, six of whom relapsed. With a median follow-up of 5 years, six patients were alive in remission, seven died of their disease (45%), in a broad range of 2 months to 8 years after diagnosis, two were lost to follow-up.</p> <p>Conclusions</p> <p>Osteosarcoma seems to be more aggressive in children under five years of age, and surgical management remains a challange.</p

Whole-body diffusion-weighted imaging for staging malignant lymphoma in children

CT is currently the mainstay in staging malignant lymphoma in children, but the risk of second neoplasms due to ionizing radiation associated with CT is not negligible. Whole-body MRI techniques and whole-body diffusion-weighted imaging (DWI) in particular, may be a good radiation-free alternative to CT. DWI is characterized by high sensitivity for the detection of lesions and allows quantitative assessment of diffusion that may aid in the evaluation of malignant lymphomas. This article will review whole-body MRI techniques for staging malignant lymphoma with emphasis on whole-body DWI. Furthermore, future considerations and challenges in whole-body DWI will be discussed

Lysophosphatidic Acid Acyltransferase β (LPAATβ) Promotes the Tumor Growth of Human Osteosarcoma

Osteosarcoma is the most common primary malignancy of bone with poorly characterized molecular pathways important in its pathogenesis. Increasing evidence indicates that elevated lipid biosynthesis is a characteristic feature of cancer. We sought to investigate the role of lysophosphatidic acid acyltransferase β (LPAATβ, aka, AGPAT2) in regulating the proliferation and growth of human osteosarcoma cells. LPAATβ can generate phosphatidic acid, which plays a key role in lipid biosynthesis as well as in cell proliferation and survival. Although elevated expression of LPAATβ has been reported in several types of human tumors, the role of LPAATβ in osteosarcoma progression has yet to be elucidated.Endogenous expression of LPAATβ in osteosarcoma cell lines is analyzed by using semi-quantitative PCR and immunohistochemical staining. Adenovirus-mediated overexpression of LPAATβ and silencing LPAATβ expression is employed to determine the effect of LPAATβ on osteosarcoma cell proliferation and migration in vitro and osteosarcoma tumor growth in vivo. We have found that expression of LPAATβ is readily detected in 8 of the 10 analyzed human osteosarcoma lines. Exogenous expression of LPAATβ promotes osteosarcoma cell proliferation and migration, while silencing LPAATβ expression inhibits these cellular characteristics. We further demonstrate that exogenous expression of LPAATβ effectively promotes tumor growth, while knockdown of LPAATβ expression inhibits tumor growth in an orthotopic xenograft model of human osteosarcoma.Our results strongly suggest that LPAATβ expression may be associated with the aggressive phenotypes of human osteosarcoma and that LPAATβ may play an important role in regulating osteosarcoma cell proliferation and tumor growth. Thus, targeting LPAATβ may be exploited as a novel therapeutic strategy for the clinical management of osteosarcoma. This is especially attractive given the availability of selective pharmacological inhibitors