Solid pseudopapillary tumor of the pancreas: Ecadherin, β-catenin, CD99 new useful markers with characteristic expression (about two case reports)

Solid pseudopapillary neoplasm of the pancreas is a rare tumor that has favorable prognosis. It poses frequently diagnostic challenges. We describe two cases of solid pseudopapillary tumor of the pancreas managed in our department between 2007 and 2011. Two females have mean age of 36.5 years. Clinical presentation include: abdominal pain, bloating and palpable abdominal mass. Tumor is localized in the head of the pancreas in one case and in the tail in the other case. The mean size of the mass was 6 cm (range: 5 to 7 cm). Surgical treatment was performed in two cases. Histological examination confirms the diagnosis of solid pseudopapillary tumor of the pancreas. Immunohistochemical analysis was concordant to the literature data especially concerning CD99 which positivity was in dot, loss of positivity of E-cadherin and nuclear staining of β-catenin. CD10 and α-1-antitrypsin were also positive. One patient was dead 3 days postoperative and neither cancer recurrence nor distant metastases were detected on the follow up of the other. However, solid pseudo-papillary tumor of the pancreas has a distinctive histological appearance; some cases are problematic requiring the use of immunohistochemistry to distinguish it from other pancreatic neoplasm which prognosis is different

VISTA/CTLA4/PD1 coexpression on tumor cells confers a favorable immune microenvironment and better prognosis in high-grade serous ovarian carcinoma

IntroductionImmunotherapy by blocking immune checkpoints programmed death/ligand (PD1/PDL1) and cytotoxic T-lymphocyte-associated protein 4(CTLA4) has emerged as new therapeutic targets in cancer. However, their efficacy has been limited due to resistance. A new- checkpoint V-domain Ig-containing suppressor of T cell activation (VISTA) has appeared, but the use of its inhibition effect in combination with antibodies targeting PDL1/PD1and CTLA4 has not been reported in ovarian cancer.MethodsIn this study, we investigated the expressions of VISTA, CTLA4, and PDL1 using immunohistochemistry (IHC)on 135 Formalin-Fixed Paraffin-Embedded (FFPE)tissue samples of High-grade serous carcinoma (HGSOC). VISTA, CTLA4, PDL1, PD1, CD8, CD4, and FOXP3 mRNA extracted from 429 patients with ovarian cancer in the Cancer Genome Atlas (TCGA) database was included as a validation cohort. Correlations between these checkpoints, tumor-infiltrating- lymphocytes (TILs), and survival were analyzed.Results and discussionCTLA4 was detectable in 87.3% of samples, VISTA in 64.7%, PD1 in 56.7%, and PDL1 in 48.1%. PDL1 was the only tested protein associated with an advanced stage (p=0.05). VISTA was associated with PDL1, PD1, and CTLA4 expressions (p=0.005, p=0.001, p=0.008, respectively), consistent with mRNA level analysis from the TCGA database. Univariate analyses showed only VISTA expression (p=0.04) correlated with overall survival (OS). Multivariate analyses showed that VISTA expression (p=0.01) and the coexpression of VISTA+/CTLA4+/PD1+ (p=0.05) were associated with better OS independently of the clinicopathological features. Kaplan-Meier analysis showed that the coexpression of the VISTA+/CTLA4+/PDL1+ and VISTA+/CTLA4+/PD1+ checkpoints on tumor cells (TCs)were associated with OS (p=0.02 and p<0.001; respectively). VISTA+/CTLA4+/PD1+ in TCs and CD4+/CD8+TILswere associated with better 2-yer OS. This correlation may refer to the role of VISTA as a receptor in the TCs and not in the immune cells. Thus, targeting combination therapy blocking VISTA, CTLA4, and PD1 could be a novel and attractive strategy for HGSOC treatment, considering the ambivalent role of VISTA in the HGSOC tumor cells

Inflammatory Bowel Disease Increases the Severity of Myocardial Infarction after Acute Ischemia–Reperfusion Injury in Mice

(1) Background: Increased risk of myocardial infarction (MI) has been linked to several inflammatory conditions, including inflammatory bowel disease (IBD). However, the relationship between IBD and MI remains unclear. Here, we implemented an original mouse model combining IBD and MI to determine IBD’s impact on MI severity and the link between the two diseases. (2) Methods: An IBD model was established by dextran sulfate sodium (DSS) administration in drinking water, alone or with oral C. albicans (Ca) gavage. IBD severity was assessed by clinical/histological scores and intestinal/systemic inflammatory biomarker measurement. Mice were subjected to myocardial ischemia–reperfusion (IR), and MI severity was assessed by quantifying infarct size (IS) and serum cardiac troponin I (cTnI) levels. (3) Results: IBD mice exhibited elevated fecal lipocalin 2 (Lcn2) and IL-6 levels. DSS mice exhibited almost two-fold increase in IS compared to controls, with serum cTnI levels strongly correlated with IS. Ca inoculation tended to worsen DSS-induced systemic inflammation and IR injury, an observation which is not statistically significant. (4) Conclusions: This is the first proof-of-concept study demonstrating the impact of IBD on MI severity and suggesting mechanistic aspects involved in the IBD–MI connection. Our findings could pave the way for MI therapeutic approaches based on identified IBD-induced inflammatory mediators

Curcumin Attenuated Neurotoxicity in Sporadic Animal Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases leading to dementia. Despite research efforts, currently there are no effective pharmacotherapeutic options for the prevention and treatment of AD. Recently, numerous studies highlighted the beneficial effects of curcumin (CUR), a natural polyphenol, in the neuroprotection. Especially, its dual antioxidant and anti-inflammatory properties attracted the interest of researchers. In fact, besides its antioxidant and anti-inflammatory properties, this biomolecule is not degraded in the intestinal tract. Additionally, CUR is able to cross the blood–brain barrier and could therefore to be used to treat neurodegenerative pathologies associated with oxidative stress, inflammation and apoptosis. The present study aimed to assess the ability of CUR to induce neuronal protective and/or recovery effects on a rat model of neurotoxicity induced by aluminum chloride (AlCl3), which mimics the sporadic form of Alzheimer’s disease. Our results showed that treatment with CUR enhances pro-oxidant levels, antioxidant enzymes activities and anti-inflammatory cytokine production and decreases apoptotic cells in AlCl3-exposed hippocampus rats. Additionally, histopathological analysis of hippocampus revealed the potential of CUR in decreasing the hallmarks in the AlCl3-induced AD. We also showed that CUR post-treatment significantly improved the behavioral, oxidative stress and inflammation in AlCl3-exposed rats. Taken together, our data presented CUR as a nutraceutical potential through its protective effects that are more interesting than recovery ones in sporadic model of AD

Orbital Tumor Revealing a Systemic Sarcoidosis

Ocular involvement is seen in approximately 25% of patients with sarcoidosis. Uveitis is the most common ocular manifestation, but sarcoidosis may involve any part of the eye. Orbital manifestations of sarcoidosis are uncommon with few series in the literature. A 65-year-old woman presented with redness of the right eye and painless, unilateral eyelid swelling. Orbital scanning revealed mass infiltrating the soft tissue of the inferior right orbital quadrant. Biopsy results showed nodular, noncaseating granulomas consistent with sarcoidosis. The complete systemic workup revealed systemic manifestations of sarcoidosis at the time of examination with hilar and mediastinal lymphadenopathies noted on CT scan. The orbital surgical treatment was followed by systemic prednisone therapy with good response. Although rare, orbital sarcoidosis must be considered in the evaluation of orbital tumors in elderly patients. A search for systemic findings should be undertaken and appropriate therapy should be instituted

PTEN Loss and Cyclin A2 Upregulation Define a PI3K/AKT Pathway Activation in Helicobacter pylori–induced MALT and DLBCL Gastric Lymphoma With Features of MALT

International audienceHelicobacter pylori infection is strongly associated with primary gastric diseases, such as extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, diffuse large B-cell lymphoma (DLBCL) with histologic evidence of MALT origin, and gastric carcinoma. The cytotoxin-associated gene A (CagA) protein behaves as a bacterial oncoprotein, promoting tumorigenesis via dysregulation of the phosphatidylinositol 3-kinase/AKT pathway (PI3K/AKT). We investigated the molecular mechanisms of PI3K/AKT pathway dysregulation in H. pylori-induced MALT and DLBCL gastric lymphoma. Immunohistochemical assays for CagA, phospho(p)-S473-AKT, PTEN, SHIP, and cyclin A2 proteins were performed on samples from 23 patients with H. pylori-positive MALT lymphoma and 16 patients with H. pylori-positive gastric DLBCL. We showed that CagA localization is correlated with the activation of the AKT pathway in both MALT and DLBCL lymphoma cells. Interestingly, we found a close association between the loss of PTEN, the overexpression of cyclin A2, and the phosphorylation of AKT in gastric MALT and DLBCL tumor cells

Overexpression of Annexin A1 Is an Independent Predictor of Longer Overall Survival in Epithelial Ovarian Cancer

International audienceBackground: Epithelial ovarian cancer (EOC) is the major gynecological cause of cancer deaths. Annexin A1 (ANXA1) protein has been implicated in the aggressiveness of several cancer types.Materials and methods: This study retrospectively assessed ANXA1 expression in epithelial cells of 156 pre-chemotherapy EOC samples and 34 normal ovarian samples from patients treated at Salah Azaiez Institute. Using immunohistochemistry, ANXA1 expression was compared in normal versus cancer samples; correlations with clinicopathological features, including overall survival, were sought.Results: Fifty-two percent of tumor samples showed epithelial ANXA1 staining versus only 26% of normal samples (Fisher's exact test, p=0.00794). Epithelial ANXA1 expression was correlated with better overall survival in both univariate and multivariate analyses.Conclusion: The possible contribution of ANXA1 overexpression to EOC outcome may be relevant to therapeutic strategies

Pharmacological Investigation of CC-LAAO, an L-Amino Acid Oxidase from Cerastes cerastes Snake Venom

International audienceSnake venom proteins, which are responsible for deadly snakebite envenomation, induce severe injuries including neurotoxicity, myotoxicity, cardiotoxicity, hemorrhage, and the disruption of blood homeostasis. Yet, many snake-venom proteins have been developed as potential drugs for treating human diseases due to their pharmacological effects. In this study, we evaluated the use of, an L-amino acid oxidase isolated from Cerastes cerastes snake venom CC-LAAO, as a potential anti-glioblastoma drug, by investigating its in vivo and in vitro pharmacological effects. Our results showed that acute exposure to CC-LAAO at 1 and 2.5 µg/mL does not induce significant toxicity on vital organs, as indicated by the murine blood parameters including aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) activities, and creatinine levels. The histopathological examination demonstrated that only at high concentrations did CC-LAAO induce inflammation and necrosis in several organs of the test subjects. Interestingly, when tested on human glioblastoma U87 cells, CC-LAAO induced a dose-dependent apoptotic effect through the H2O2 generated during the enzymatic reaction. Taken altogether, our data indicated that low concentration of CC-LAAO may be safe and may have potential in the development of anti-glioblastoma agents

Cutaneous leiomyosarcoma on the trunk: unusual presentation with an aggressive course – case report and review of literature

Primary cutaneous leiomyosarcoma (PCL) are soft-tissue sarcoma, arising in the dermis, with or without extension into the subcutis. They are thought to have an indolent course compared to their subcutaneous counterparts, they may recur but rarely metastases. We report the case of a patient with a PCL arising in the anterior trunk wall who developed pulmonary, bone and retroperitoneal metastases 6 years after wide surgical excision of the primary tumor