Prognostic Impact of Src, CDKN1B, and JAK2 Expression in Metastatic Breast Cancer Patients Treated with Trastuzumab.

Background: Src, CDKN1B, and JAK2 play a crucial role in the coordination of cell signaling pathways. In the present study, we aim to investigate the prognostic significance of these biomarkers in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab (T).

Methods: Formalin-fixed paraffin-embedded tumor tissue samples from 197 patients with HER2-positive MBC treated with T were retrospectively collected.

Endothelial progenitor cells as a cardiometabolic risk factor marker in prediabetes.

Objective: Endothelial progenitor cells (EPCs) have recently been considered as a potential novel marker of vascular integrity, atherosclerosis and cardiovascular risk. This study was performed to investigate the main determinants of EPC levels in individuals with prediabetes.

Design: Thirty-nine participants with newly diagnosed prediabetes were enrolled.

Feasibility of Induction Docetaxel, Cisplatin, 5-Fluorouracil, Cetuximab (TPF-C) Followed by Concurrent Cetuximab Radiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma.

Purpose: To report our experience with a sequential regimen of induction TPF-C followed by radioimmunotherapy with cetuximab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Patients And Methods: Toxicity and outcome was retrospectively analyzed in 22 patients receiving sequential therapy with induction TPF-C followed by radioimmunotherapy between October 2008 and December 2011. Outcome was estimated using Kaplan-Meier analyses.

XELIRI-bevacizumab versus FOLFIRI-bevacizumab as first-line treatment in patients with metastatic colorectal cancer: a Hellenic Cooperative Oncology Group phase III trial with collateral biomarker analysis.

Background: The aim was to compare two standard chemotherapy regimens combined with bevacizumab as first-line treatment in patients with metastatic colorectal cancer.

Methods: Patients previously untreated for metastatic disease were randomized in: group A (irinotecan, capecitabine, bevacizumab, every 3 weeks; XELIRI-bevacizumab) and group B (irinotecan, leucovorin, fluorouracil, bevacizumab, every 2 weeks; FOLFIRI-bevacizumab). Primary endpoint was progression-free survival (PFS).

Gingival bleeding and jaw bone necrosis in patients with metastatic renal cell carcinoma receiving sunitinib: report of 2 cases with clinical implications.

There is emerging evidence that oral mucositis/stomatitis is a common adverse effect of sunitininb antiangiogenic therapy in patients with metastatic renal cell carcinoma (mRCC). In addition, a case of sunitinib-related jaw osteonecrosis was recently described. We report on 2 patients with mRCC treated with sunitinib.

Toll/interleukin-1 receptor member ST2 exhibits higher soluble levels in type 2 diabetes, especially when accompanied with left ventricular diastolic dysfunction.

Background: Soluble ST2, a member of the of the Toll/IL-1 superfamily, is a novel biomarker with exceptional predictive value in heart failure and myocardial infarction- related mortality as well as in acute dyspneic states. Soluble ST2 is considered a decoy receptor of IL 33 that blocks the protective effects of the cytokine in atherosclerosis and cardiac remodeling. In the present study we investigated the differences in the levels of soluble ST2, BNP and hs-CRP between healthy controls and patients with type 2 diabetes with and without left ventricular diastolic dysfunction.

The novel member of the BCL2 gene family, BCL2L12, is substantially elevated in chronic lymphocytic leukemia patients, supporting its value as a significant biomarker.

BCL2L12 is a recently identified gene belonging to the BCL2 family, members of which are implicated in hematologic malignancies, including chronic lymphocytic leukemia (CLL). The aim of this study was to analyze the mRNA expression of the novel apoptosis-related gene BCL2L12 in patients with CLL and to examine its prognostic and predictive value and potential clinical application as a novel molecular biomarker for CLL. For this purpose, total RNA was isolated from peripheral blood of 65 CLL patients and 23 healthy donors.

No significant improvement in the outcome of patients with Waldenström's macroglobulinemia treated over the last 25 years.

The treatment of Waldenström's macroglobulinemia (WM) has changed over the last decades, mainly because of the introduction of nucleoside analogues and of rituximab while novel agents such as bortezomib have been recently introduced. We performed an analysis to investigate whether the outcome of patients with WM has improved over the last years, compared to that of patients who started treatment before new drugs became widely available, especially as part of the frontline treatment. We analyzed 345 symptomatic patients with WM: 130 who initiated treatment before and 215 who started treatment after January 1, 2000.

Prognostication of the high-risk WM patient.

Waldenström's macroglobulinemia is characterized by a protracted course in most patients and the median survival may be long. However, a subset of patients may present with more aggressive disease that is associated with short survival. In order to better characterize these "poor-risk" patients, we identified patients who died within 2 years from the initiation of front-line treatment.

Abnormalities of DNA repair mechanisms in common hematological malignancies.

DNA repair is an important defense mechanism that faces the difficult task of protecting the genome from the constant assaults caused by endogenous and exogenous agents. Since DNA repair mechanisms are responsible for correcting DNA damage and preserving genomic integrity, it is obvious that abnormalities of these mechanisms may result in neoplastic transformation. Hematological malignancies are characterized by genomic instability that is possibly related to underlying defects in DNA repair.

Adiponectin levels and expression of adiponectin receptors in isolated monocytes from overweight patients with coronary artery disease.

Background: Adiponectin has insulin-sensitizing and anti-atherosclerotic effects, partly mediated through its action on monocytes. We aimed to determine adiponectin levels and expression of its receptors (AdipoR1 and AdipoR2) in peripheral monocytes from overweight and obese patients with coronary artery disease (CAD).

Methods: Fifty-five overweight/obese patients, suspected for CAD, underwent coronary angiography: 31 were classified as CAD patients (stenosis ≥ 50% in at least one main vessel) and 24 as nonCAD.

A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: a Hellenic Cooperative Oncology Group study.

Background: Colon cancer is a public health problem worldwide. Adjuvant chemotherapy after surgical resection for stage III colon cancer has been shown to improve both progression-free and overall survival, and is currently recommended as standard therapy. However, its value for patients with stage II disease remains controversial.

Cutaneous involvement in angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive non-Hodgkin's nodal peripheral T-cell lymphoma characterized by general lymphadenopathy, night sweats, fever, hepatosplenomegaly, polyclonal hypergammaglobulinemia, and cutaneous involvement. We present a rare case of AITL cutaneous involvement mimicking toxic erythema recurring with AITL relapse and suggesting a precursor of disease progression.

Irinotecan/fluorouracil/leucovorin or the same regimen followed by oxaliplatin/fluorouracil/leucovorin in metastatic colorectal cancer.

Background: This study reports the long-term follow-up of patients with metastatic colorectal cancer (CRC) participating in a randomised phase II study that compared the efficacy and toxicity of the combination of irinotecan (IRI), fluorouracil (FU) with leucovorin (LV) (arm A) versus sequential chemotherapy with IRI plus FU/LV followed by oxaliplatin (OXA) plus FU/LV (arm B) as first line therapy.

Materials And Methods: Intent-to-treat analysis was performed on 417 patients (211 in arm A and 206 in arm B). Treatment schedules of weekly IRI 80 mg/m(2) or OXA 45 mg/m(2) plus LV 200 mg/m(2) immediately followed by intravenous bolus FU 450 mg/m(2) for 6 weeks were followed by a 2-week rest period.

Hypoxia-inducible factors in mantle cell lymphoma: implication for an activated mTORC1→HIF-1α pathway.

Aberrant activation of phosphoinositide-3 kinase/Akt (PI3K/Akt) and mammalian target of rapamycin (mTOR) signaling is implicated in the pathogenesis of mantle cell lymphoma (MCL). We previously showed oncogenic activation of PI3K/Akt pathway in a subset of MCL patients. In this study, we investigated downstream the immunohistochemical expression of (Ser2448)pmTOR [indicative of mTOR complex 1 (mTORC1) activation status] as well as of hypoxia-inducible factor 1 alpha (HIF-1α), hypoxia-inducible factor 2 alpha (HIF-2α), p53, and p21 in the same series of MCL patients.

Subcutaneous glucose monitoring with GlucoDay: comparison of the results to those obtained with the endocrine artificial pancreas.

Objective: This study was undertaken to assess the accuracy of GlucoDay- a portable detector of subcutaneous glucose--by comparing the results to those obtained by Biostator an established and reliable method for continuous glucose measurement in whole blood.

Design: Subjects with type 1 diabetes (n:6), subjects with type 2 diabetes (n:6), and six healthy controls were studied for 24 hours; they consumed three main meals. The GlucoDay was connected to the subjects by inserting a microfibre probe into the periumbilical subcutaneous area, whilst the Biostator was inserted by a double-lumen catheter into an antecubital vein.

Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism.

Objective: Although clinical hyperthyroidism (HR) is associated with insulin resistance, the information on insulin action in subclinical hyperthyroidism (SHR) is limited.

Design And Methods: To investigate this, we assessed the sensitivity of glucose metabolism to insulin in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes) in 12 euthyroid subjects (EU), 16 patients with HR, and 10 patients with SHR.

Results: HR and SHR patients displayed higher postprandial glucose levels (area under the curve, AUC(0)(-)(300) 32,190±1067 and 31,497±716,mg/dl min respectively) versus EU (27,119±1156 mg/dl min, P<0.

Rosuvastatin-induced thrombocytopenia.

Rosuvastatin, a statin indicated for patients with primary hypercholesterolemia, mixed dyslipidemia and familial hypercholesterolemia, is well tolerated by most patients. Its most common adverse effects are gastrointestinal derangement, muscle aches and hepatitis. One rare complication of statin treatment is severe thrombocytopenia.

High serum lactate dehydrogenase adds prognostic value to the international myeloma staging system even in the era of novel agents.

Objectives: High serum lactate dehydrogenase (LDH) is associated with features of advanced disease and inferior survival in multiple myeloma. It is however unclear whether LDH adds to the prognostic value of International Staging System (ISS) and whether it retains its prognostic significance in patients who are exposed to novel agent-based therapies.

Patients/methods: To address these issues we analyzed 996 consecutive symptomatic patients who were included in the database of the Greek Myeloma Study Group and received frontline treatment between January 1, 1995 and December 31, 2008.