Circulating autoantibodies to alpha-enolase (ENO1) and far upstream element-binding protein 1 (FUBP1) are negative prognostic factors for pancreatic cancer patient survival.

Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis due to a lack of early diagnostic markers and effective therapy. In PDA patients, the glycolytic enzyme and plasminogen receptor alpha-enolase (ENO1) and the transcription factor far upstream element-binding protein 1 (FUBP1) are upregulated and elicit the production of autoantibodies (aAb) that discriminate healthy subjects from PDA patients, with the latter mostly directed to post-translational phosphorylated isoforms. Here, the correlation of prognosis with circulating ENO1 and FUBP1aAb, and their protein tissue expression was analyzed in PDA patients. Circulating ENO1 and FUBP1 aAb was analyzed in two cohorts of PDA patients by ELISA (n = 470), while tissues expression was observed by immunohistochemistry (n = 45). Overall survival (OS) was estimated using the Kaplan-Meier method, while the Cox model was used to estimate the hazard ratios (HR) adjusted for the main prognostic factors. Logistic models were applied to assess associations between death and its risk indicators. All statistical analyses were performed with Stata version 15. Unlike ENO1 aAb, there was a significant correlation between FUBP1 aAb and FUBP1 expression in tumors (p = 0.0268). In addition, we found that high ENO1 (p = 0.016) and intermediate FUBP1 aAb levels (p = 0.013) were unfavorable prognostic factors. Notably, it was found that high anti-FUBP1 aAb level is a good prognostic marker for tail-body PDA (p = 0.016). Our results suggest that different levels of circulating aAb to ENO1 and FUBP1 predict a poor outcome in PDA patients and can be used to improve therapeutic strategies.

Treatment with Beta-Blockers and ACE-Inhibitors in Breast Cancer Patients Receiving Adjuvant Trastuzumab-Based Therapy and Developing Mild Cardiac Toxicity: A Prospective Study.

BACKGROUND: Angiotensin Converting Enzyme inhibitors (ACEis) and beta-blockers (BB) are suggested to prevent and treat trastuzumab-related cardiac toxicity. We performed a prospective clinical trial in women experiencing mild cardiac toxicity (MCT) while on adjuvant treatment with trastuzumab. METHODS: MCT was defined as an asymptomatic absolute decrease in LVEF of ≥ 10 percentage units to >50%. Treatment consisted of enalapril 2.5 mg bid and carvedilol 3.75 mg bid, which were up-titrated to 10 mg bid for the enalapril and 6,25 mg bid of carvedilol. In patients receiving study drug, the primary study end-point was LVEF recovery, which was defined as a post-trastuzumab LVEF returning to no less than -5 percentage points of the baseline value. RESULTS: 103 patients were enrolled, 100 started trastuzumab, and 98 completed the planned treatment. Sixteen patients (16%) had MCT and received study drugs until trastuzumab completion. None of these patients achieved a post-trastuzumab LVEF recovery. Nevertheless, treated patients had significantly higher median LVEF recovery from nadir to post-trastuzumab LVEF in (8% points vs. 4% points, respectively, p = 0.004), resulting in no difference in post-treatment LVEF values compared to patients without MCT. CONCLUSION: Treatment of MCT with ACEis and BB allows faster LVEF recovery from nadir values and should be further studied in this setting.

Investigational ErbB-2 tyrosine kinase inhibitors for the treatment of breast cancer.

INTRODUCTION: ErbB2 overexpression and/or gene amplification is present in 20% of all breast cancers and characterizes an aggressive form of this disease. Despite the availability of several active drugs that have yielded substantial survival improvements, most patients with ErbB2-positive metastatic disease will develop tumor progression, either because of primary or acquired resistance. Therefore, research has focused on drugs that can more efficiently interfere with ErbB2 and with other members of the epidermal growth factor receptor family. AREAS COVERED: This review focuses on those investigational drugs that inhibit ErbB2 tyrosine kinase activity (TKIs) for treating breast cancer. EXPERT OPINION: ErbB-targeting TKIs show encouraging activity in patients with ErbB-positive tumors that are resistant to conventional ErbB-therapies (mostly trastuzumab), confirming pre-clinical observations. Efficient interference with the ErbB-network signaling implies also a potential use in ErbB2-normal tumors, where the phenotype is sustained by ErbB-aberrant signaling. Finally, early data suggests that ErbB-targeting TKIs could be active in treating patients with activating ErbB2 mutations. Ongoing and future research efforts should elucidate what is, according to the peculiarities of these compounds, their positioning in the treatment of women with breast cancer.

Complete remission of paraneoplastic vanishing bile duct syndrome after the successful treatment of Hodgkin's lymphoma: a case report and review of the literature.

BACKGROUND: Vanishing bile duct syndrome has been associated with different pathologic conditions (adverse drug reactions, autoimmune diseases, graft versus host disease, and cancer). Though its causes are unknown, an immune-related pathogenesis is the most likely one. Vanishing bile duct syndrome can evolve to hepatic failure and, eventually, to death. The treatment is uncertain, but it needs the resolution of the underlying pathologic condition. CASE PRESENTATION: We describe the association of Hodgkin's lymphoma with a syndrome characterized by cholestasis, aminotransferase elevation and an histological picture of bile duct loss. All other causes of hepatic function impairment were excluded (in particular, drugs, viral and autoimmune related diseases) eventually leading to the diagnosis of vanishing bile duct syndrome. Despite the fact that the dysfunction is not caused by hepatic Hodgkin's lymphoma involvement, liver impairment can limit the optimal therapy of Hodgkin's lymphoma. A treatment consisting of ursodeoxycholic acid, prednisone, and full dose chemotherapy restored hepatic function and achieved complete and long-lasting remission of Hodgkin's lymphoma. CONCLUSION: We reviewed all case reports showing that vanishing bile duct syndrome is a dismal paraneoplastic syndrome being fatal in a high proportion of patients if not adequately treated. Indeed, this syndrome requires both an early recognition and an appropriate aggressive treatment consisting of full dose upfront chemotherapy which is the only way to achieve a resolution of the vanishing bile duct syndrome. Delayed or reduced intensity treatments unfavorably correlate with survival.