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Arias-Pulido H.,University of New Mexico | Royce M.,University of New Mexico | Gong Y.,University of Houston | Joste N.,University of New Mexico | And 7 more authors.
Breast Cancer Research and Treatment | Year: 2010

GPR30 is a novel G protein-coupled estrogen receptor (ER) associated with metastases in breast cancer (BC) and poor survival in endometrial and ovarian tumors. The association of GPR30 expression with inflammatory breast cancer (IBC), an aggressive and commonly hormone-independent form of BC, has not been studied. GPR30, ER, progesterone receptor (PR), epidermal growth factor receptor (EGFR), and HER-2 expression were assessed by immunohistochemistry (and FISH for HER-2) in 88 primary IBCs. GPR30 expression was correlated with patient overall survival (OS), disease-free survival (DFS), pathologic variables, and other biomarkers. GPR30 expression was found in 69% of IBC cases. ER, PR, HER-2, and EGFR were found in 43, 35, 39, and 34% of IBC cases, respectively. GPR30 expression correlated inversely with ER expression (P = 0.02). Co-expression of ER and GPR30 was found in 24% of IBC samples; 19% expressed only ER and 46% expressed only GPR30. Univariate analysis showed no association between GPR30 expression and OS or DFS. However, co-expression of ER and GPR30 was associated with improved OS (P < 0.03) and marginally with DFS (P < 0.06); the absence of both ER and GPR30 was associated with worse OS and DFS (P = 0.03 for both). Multivariate analysis identified ER as an independent prognostic factor of OS (P = 0.008) and DFS (P = 0.02). The majority of IBC tumors are GPR30-positive, suggesting that estrogen signaling may be active in ER-negative IBC patients. These findings suggest potential new therapeutic targets for IBC such as novel endocrine agents or direct modulation of GPR30. © 2009 Springer Science+Business Media, LLC. Source


Bouzid K.,Center Pierre et Marie Curie | Bedairia N.,Center des Innovations Therapeutiques en Oncologie et Hematologie | Marty M.,Center des Innovations Therapeutiques en Oncologie et Hematologie
Pathologie Biologie | Year: 2012

Advances in bioengineering have lead to the possibility to conduct large scale production of monoclonal antibodies (MoAB) and to reduce progressively the murine component from 30% (chimeric MoAB) to 5% (humanized MoAB) to 0% (human MoAB). Three types of extracellular components are targeted in solid tumours: (1) Growth factors with transmembrane tyrosine kinase receptors either of tumour cells (IGF1) or endothelial cells (Bevacizumab). Bevacizumab has activity additive to that of chemotherapy in advanced colorectal, non squamous lung, ovarian, metastatic breast cancers and glioblastomas; (2) Extracellular domain of those transmembrane receptors: EGFR in colorectal cancer if no activating of KRAS with cetuximab and panitumumab, head and neck carcinomas with radiotherapy, and probably squamous lung cancers. Anti-ERBB2 MoAb are now a constitutive part of therapy of ERBB2 positive breast cancers at any stage; (3) Differenciation cluster regulating relationship ot tumour and stromal cells and in particular immunologic effectors. This is the case of anti-CTLA4 MoAB ipilimumab which activates and amplifies immunological cytotoxic response against melanoma with improved survival. These activities are achieved to the expense of class, target related toxicity conditioned by expression of the target on normal cells and or mechanism of action (immunological toxicity with ipilimumab). Of note a synergistic or additive activity with valid treatment regimens of targeted cancers and now targeted small molecules. © 2012. Source


Bacigalupo A.,IRCCS San Martino IST | Schrezenmeier H.,Institute Klinische und Transfusion Medizin | Tichelli A.,Kantonspital | Locasciulli A.,Ospedale San Camillo | And 10 more authors.
Haematologica | Year: 2012

Background Bone marrow has been shown to be superior to peripheral blood, as a stem cell source, in young patients (<20 years of age) with acquired aplastic anemia undergoing a matched sibling transplant. The aim of this study was to test whether this currently also holds true for older patients with acquired aplastic anemia. Design and Methods We analyzed 1886 patients with acquired aplastic anemia who received a first transplant from a human leukocyte antigen identical sibling between 1999 and 2009, with either bone marrow (n=1163) or peripheral blood (n=723) as the source of stem cells. Results In multivariate Cox analysis negative predictors for survival were: patient's age over 20 years (RR 2.0, P<0.0001), an interval between diagnosis and transplantation of more than 114 days (RR 1.3, P=0.006), no anti-thymocyte globulin in the conditioning (RR 1.6, P=0.0001), a conditioning regimen other than cyclophosphamide (RR=1.3, P=0.008) and the use of peripheral blood as the source of stem cells (RR 1.6, P<0.00001). The survival advantage for recipients of bone marrow rather than peripheral blood was statistically significant in patients aged 1-19 years (90% versus 76% P<0.00001) as well as in patients aged over 20 years (74% versus 64%, P=0.001). The advantage for recipients of bone marrow over peripheral blood was maintained above the age of 50 years (69% versus 39%, P=0.01). Acute and chronic graft-versus-host disease were more frequent in peripheral blood transplants. Major causes of death were graft-versus-host disease (2% versus 6% in bone marrow and peripheral blood recipients, respectively), infections (6% versus 13%), and graft rejection (1.5% versus 2.5%). Conclusions This study shows that bone marrow should be the preferred stem cell source for matched sibling transplants in acquired aplastic anemia, in patients of all age groups. © 2012 Ferrata Storti Foundation. Source


Arias-Pulido H.,University of New Mexico | Chaher N.,Center Pierre et Marie Curie | Gong Y.,University of Houston | Qualls C.,University of New Mexico | And 2 more authors.
BMC Cancer | Year: 2012

Background: Inflammatory breast cancer (IBC) is a highly angiogenic disease; thus, antiangiogenic therapy should result in a clinical response. However, clinical trials have demonstrated only modest responses, and the reasons for these outcomes remain unknown. Therefore, the purpose of this retrospective study was to determine the prognostic value of protein levels of vascular endothelial growth factor (VEGF-A), one of the main targets of antiangiogenic therapy, and its receptors (VEGF-R1 and -R2) in IBC tumor specimens.Patients and Methods: Specimens from IBC and normal breast tissues were obtained from Algerian patients. Tumor epithelial and stromal staining of VEGF-A, VEGF-R1, and VEGF-R2 was evaluated by immunohistochemical analysis in tumors and normal breast tissues; this expression was correlated with clinicopathological variables and breast cancer-specific survival (BCSS) and disease-free survival (DFS) duration.Results: From a set of 117 IBC samples, we evaluated 103 ductal IBC tissues and 25 normal specimens. Significantly lower epithelial VEGF-A immunostaining was found in IBC tumor cells than in normal breast tissues (P <0.01), cytoplasmic VEGF-R1 and nuclear VEGF-R2 levels were slightly higher, and cytoplasmic VEGF-R2 levels were significantly higher (P = 0.04). Sixty-two percent of IBC tumors had high stromal VEGF-A expression. In univariate analysis, stromal VEGF-A levels predicted BCSS and DFS in IBC patients with estrogen receptor-positive (P <0.01 for both), progesterone receptor-positive (P = 0.04 and P = 0.03), HER2+ (P = 0.04 and P = 0.03), and lymph node involvement (P <0.01 for both). Strikingly, in a multivariate analysis, tumor stromal VEGF-A was identified as an independent predictor of poor BCSS (hazard ratio [HR]: 5.0; 95% CI: 2.0-12.3; P <0.01) and DFS (HR: 4.2; 95% CI: 1.7-10.3; P <0.01).Conclusions: To our knowledge, this is the first study to demonstrate that tumor stromal VEGF-A expression is a valuable prognostic indicator of BCSS and DFS at diagnosis and can therefore be used to stratify IBC patients into low-risk and high-risk groups for death and relapses. High levels of tumor stromal VEGF-A may be useful for identifying IBC patients who will benefit from anti-angiogenic treatment. © 2012 Arias-Pulido et al.; licensee BioMed Central Ltd. Source


Bouras A.F.,Center Hospitalier Of Bethune | Marin H.,Lille University Hospital Center | Bouzid C.,Center Pierre et Marie Curie | Pruvot F.-R.,Lille University Hospital Center | And 2 more authors.
Langenbeck's Archives of Surgery | Year: 2016

Background: Life-threatening postoperative pancreatic fistula (LTPOPF) is the most feared complication after pancreatoduodenectomy (PD). Although completion pancreatectomy (CP) is usually performed when radiological management fails, the associated morbidity and mortality rates remain high. Here, we reviewed pancreas-preserving alternatives to CP. Methods: The PubMed database was systematically searched for publications between 1983 and 2014, describing pancreas-preserving surgical treatment of the pancreas remnant (PR) after reintervention in a context of post-PD LTPOPF. Results: A total of 12 articles including 140 patients were reviewed. Six different types of pancreas-preserving treatment were described: external wirsungostomy, simple drainage of the PF, closure of pancreatic stump, internal wirsungostomy, partial CP, and salvage pancreatogastrostomy after major leakage of a pancreatojejunostomy. The overall median survival rate was 75 % but rose to 83 % when patients undergoing only surgical drainage of the fistula were excluded. The median complication rate was 75 %, and the median length of hospital stay was 41.5 days. Further reintervention was required for 25 % of the patients. The median incidence of late diabetes was 22.5 %. The incidence of exocrine insufficiency ranged from 0 to 100 % depending on the intervention. Conclusion: Pancreas-preserving surgical management of the PR after LTPOPF can be performed with acceptable mortality and morbidity. These data suggest that CP should have a more precisely specified role in the management algorithm and should not be performed systematically. © 2015, Springer-Verlag Berlin Heidelberg. Source

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