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The 78-kDa glucose-regulated protein (GRP78) is a stress induced heat shock protein which, under limiting conditions, functions as a cell surface signaling receptor. Tumor cells are considered to be subjected to a physiologically stressful microenvironment due to their excessive growth. The role of GRP78 in tumor survival has been of notable interest. The present study aimed to assess the potential prognostic and predictive value of cell surface GRP78 expression in breast cancer tumor cells. Cell surface and cytoplasmic expression of GRP78 was examined by immunohistochemical staining of GRP78 in breast cancer archival paraffin-embedded tumor specimens. The cohort studied included breast cancer patients with operable T1,2, estrogen receptor-positive, node-negative cancer who were assessed using the Oncotype DX gene profile, as well as patients with locally advanced disease prior to and following neoadjuvant systemic treatment. GRP78 values were compared between the 2 groups, and prior to and following systemic treatment. Association analyses between GRP78 expression and prognostic markers were also performed. Cox regression analysis was used to examine the impact of these variables on disease-free survival (DFS). No differences in cytoplasmic GRP78 expression were observed. By contrast, the rates of cell surface GRP78 expression were 74.1% in the early stage operable patients, 36% in neoadjuvant systemic treatment patients prior to treatment and 62.5% in patients following systemic treatment (P<0.039). Positive cell surface GRP78 expression was associated with increased expression of the progesterone receptor (P=0.024), p53 expression (P=0.022) and improved DFS (P=0.047). In the case of GRP78 positivity, a trend for a superior response to chemotherapy was observed (P=0.19). The results of the present study indicated that cell surface GRP78 may be used as a marker for good prognosis in breast cancer and a potential marker for response to chemotherapy.

Natural killer (NK) cells belong to the innate lymphoid cells. Their cytotoxic activity is regulated by the delicate balance between activating and inhibitory signals. NKp46 is a member of the primary activating receptors of NK cells. We previously reported that the NKp46 receptor is involved in the development of type 1 diabetes (T1D). Subsequently, we hypothesized that blocking this receptor could prevent or hinder disease development. To address this goal, we developed monoclonal antibodies for murine NKp46. One mAb, named NCR1.15, recognizes the mouse homologue protein of NKp46, named Ncr1, and was able to down-regulate the surface expression of NKp46 on primary murine NK cells following antibody injection in vivo. Additionally, NCR1.15 treatments were able to down-regulate cytotoxic activity mediated by NKp46, but not by other NK receptors. To test our primary assumption, we examined T1D development in two models, non-obese diabetic mice and low-dose streptozotocin. Our results show a significantly lower incidence of diabetic mice in the NCR1.15-treated group compared to control groups. This study directly demonstrates the involvement of NKp46 in T1D development and suggests a novel treatment strategy for early insulitis.

IntroductionA gastrosplenic fistula (GSF) is a very rare complication that arises mainly from a splenic or gastric large cell lymphoma. The proximity of the gastric fundus to the enlarged fragile spleen may facilitate the fistulisation. This complication can lead to massive bleeding, which, though uncommon, may be lethal. We present a patient with massive upper gastrointestinal bleeding secondary to a GSF.Case presentationWe present a 48-year-old man with a refractory diffuse large B-cell lymphoma who was admitted to our hospital due to hematemesis. On arrival, he was in hemorrhagic shock, and was taken directly to the intensive care unit. The source of bleeding could not be identified on gastroscopy, the patient remained hemodynamically unstable and a laparotomy was performed.A fistula between a branch of the splenic artery and the stomach was identified. The stomach appeared to be involved in the malignant process. After subtotal gastrectomy and splenectomy, the bleeding was controlled. After stabilization, the patient was admitted to the intensive care unit, and 24 hours later was discharged in stable condition.DiscussionWe describe a fistula between a branch of the splenic artery and the stomach, which was accompanied by massive bleeding. An emergency laparotomy saved the patient's life.ConclusionThe purpose of this report is to alert physicians that surgical intervention can be lifesaving in this rare malignant condition. A literature review focusing on the presenting symptoms and the epidemiology of GSF is presented.

We have scrutinized a previously analyzed cohort of classical Hodgkin lymphoma patients for evidence of a CD20 over-expression. This was pursued in order to determine whether all the 24 (12.6%) CD20+++ patients had clinical and/or biological profiles which would warrant a separate consideration and treatment or would carry a different outcome from our 166 CD20 (-) classical Hodgkin lymphoma patients. Except for an older age and a significantly lower expression of non-sialyl-CD15 antigen, both previously described in classical Hodgkin lymphoma, no justification to exclude these CD20+++ patients from the cohort at large is apparent. We suggest that the generally accepted view to the contrary be revised. In addition, we propose alternative interpretations for the low expression of CD20 found in a majority of Hodgkin-Reed-Sternberg cells in classical Hodgkin lymphoma.