Exploring the time-dependent regulatory potential of microRNAs in breast cancer cells treated with proteasome inhibitors.

PURPOSE: Breast cancer (BrCa) is a predominant type of cancer with a disparate molecular nature. MicroRNAs (miRNAs) have emerged as promising key players in the regulation of pathological processes in BrCa. Proteasome inhibitors (PIs) emerged as promising anticancer agents for several human malignancies, including BrCa, inhibiting the function of the proteasome. Aiming to shed light on the miRNA regulatory effect in BrCa after treatment with PIs, we used two PIs, namely bortezomib and carfilzomib. MATERIALS AND METHODS: Four BrCa cell lines of distinct molecular subtypes were treated with these PIs. Cell viability and IC50 concentrations were determined. Total RNA was extracted, polyadenylated, and reversely transcribed. Next, the levels of specific miRNAs with a significant role in BrCa were determined using relative quantification, and their regulatory effect was assessed. RESULTS: High heterogeneity was discovered in the levels of miRNAs in the four cell lines, after treatment. The miRNA levels fluctuate with distinct patterns, in 24, 48, or 72 hours. Interestingly, miR-1-3p, miR-421-3p, and miR-765-3p appear as key molecules, as they were found deregulated, in almost all combinations of cell lines and PIs. In the SK-BR-3 cell line, the majority of the miRNAs were significantly downregulated in treated compared to untreated cells, with miR-21-5p being the only one upregulated. Finally, various significant biological processes, molecular functions, and pathways were predicted to be affected. CONCLUSIONS: The diversity of pathways predicted to be affected by the diversity in miRNA expression after treatment with PIs paves the way for the recognition of new regulatory axes in BrCa.

Effective panitumumab treatment in patients with heavily pre-treated metastatic colorectal cancer: a case series.

In heavily pre-treated patients with metastatic colorectal cancer (mCRC), further chemotherapy has not demonstrated efficacy. Panitumumab is indicated as monotherapy treatment of epidermal growth factor receptor (EGFR)-expressing, Kirsten (K)-RAS wild-type metastatic colorectal cancer after failure of fluoropyrimidine-, oxaliplatin- and irinotecan-containing regimens. However, panitumumab has not been specifically evaluated in patients following failure of a bevacizumab-containing regimen. One female and two male patients with mCRC presented with tumour recurrence in the para-aortic lymph nodes, the liver and the local presacral lymph nodes, respectively. The patients were confirmed to have K-RAS wild-type-expressing tumours. Following the failure of bevacizumab-containing chemotherapy regimens, all three patients received panitumumab monotherapy. Panitumumab was well-tolerated. All the patients responded to panitumumab monotherapy in this late-stage setting. This patient series suggests that panitumumab can improve patient outcomes and may be an alternative treatment option in patients with mCRC who have received prior treatment with bevacizumab plus chemotherapy.

A giant mesenteric lipoblastoma in an 18-month old infant: a case report and review of the literature.

Infantile lipoma (or lipoblastoma) of the mesentery is an extremely rare benign tumor of embryonal fat, with 15 cases reported in the English literature until today and only three of them arise from the ileum mesentery. We report an 18-month old boy presenting with a palpable intraabdominal mass arising from the ileum mesentery. Histopathologic and cytogenetic studies confirmed the diagnosis of mesenteric lipoblastoma (or infantile lipoma). Complete excision of the mass was performed. A follow-up examination consisting of physical examination and an abdominal ultrasound at 30 months postoperatively revealed no recurrence. We also present a review of the English literature regarding the presentation and management of mesenteric lipoblastomas in children.

Increased fluorodeoxyglucose uptake following endovascular abdominal aortic aneurysm repair: a predictor of endoleak?

The main criterion for abdominal aortic aneurysm (AAA) repair is an AAA diameter >/=5.5 cm. However, some AAAs rupture when they are smaller. Size alone may therefore not be a sufficient criterion to determine rupture risk. Fluorodeoxyglucose (FDG) uptake is increased in the presence of inflammation and it was suggested that this may be a better predictor of rupture risk than AAA size. Furthermore, increased FDG uptake following endovascular AAA repair may be an indirect predictor of continuous AAA sac enlargement due to the presence of an endoleak (even if this is not detected by imaging modalities) and/or increased AAA rupture risk. The role of FDG uptake needs to be explored further in the management of AAAs.

Cardiovascular events in chronic dialysis patients: emphasizing the importance of vascular disease prevention.

Cardiovascular disease is the leading cause of death in both chronic kidney disease and peritoneal dialysis/hemodialysis patients. Vascular disease prevention in these patients is therefore important to reduce the incidence of cardiovascular events and the high morbidity and mortality. This Editorial discusses the traditional, (1) smoking, (2) dyslipidemia, (3) body mass index, (4) glycemic control and (5) blood pressure, and non-traditional, (1) anemia, (2) vitamin D/hyperparathyroidism, (3) calcium/phosphorus metabolism and (4) magnesium, risk factors in renal patients. Current evidence does not support routine statin use and antiplatelet medication to dialysis patients. Patient compliance and adherence to proposed measures could be essential to reduce cardiovascular events and mortality rates in this high-risk population.

Biweekly gemcitabine (GEM) in combination with erlotinib (ERL): an active and convenient regimen for advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer remains a disease of high mortality and one of the most frustrating, resistant solid neoplasms to treat. The aim of this study was to evaluate a biweekly gemcitabine plus daily erlotinib regimen in patients with advanced (stage III-IV) pancreatic cancer in terms of overall survival and time to progression of the disease. The secondary aim was to record treatment related toxicities. PATIENTS AND METHODS: Twenty-seven patients with metastatic non-operable pancreatic adenocarcinoma, stage III-IV, consented to receive chemotherapy with gemcitabine and erlotinib. Patients received first-line treatment with gemcitabine (2 g/m(2) via 90 min i.v. infusion every two weeks) and 100 mg erlotinib per os every day, for at least 12 consecutive courses (6 cycles). Treatment was discontinued at disease progression and/or serious toxicity. RESULTS: The objective response rate was 25.9% (95% confidence interval [CI]: 11.1-46.3%) and the stable disease rate was 59.3% (95% CI: 38.8-77.6%). The one-year overall survival was 20%. The median overall survival and time to progression at the time of assessment was 7.5 months (95% CI: 3.6-42 months) and 5.5 months (95% CI: 1.5-10 months), respectively. Overall survival and time to progression were related to response (p<0.001), while time to progression was further related to disease stage (p=0.011). No grade 4 haematological or non-haematological toxicities were observed. CONCLUSION: The biweekly regimen of gemcitabine plus erlotinib has similar toxicity and efficacy to weekly administration, presenting both patients and hospital resource departments with a clearly more convenient therapy alternative.

Emerging indications for statins: a pluripotent family of agents with several potential applications.

Statins are pluripotent agents exhibiting multiple non-lipid-lowering actions. Besides their established role in the management of hypercholesterolemia, statins may also have beneficial actions in other pathological conditions, namely: a) osteoporosis and osteoporosis-related bone fractures, b) cancer, c) solid organ transplantation, d) cerebrovascular events (transient ischemic attack and stroke episodes), e) various neurological disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis, f) cardiac arrhythmias and heart failure, g) renal diseases, h) rheumatoid arthritis, i) autoimmune diseases, j) sepsis, and k) allergic asthma. We reviewed the literature searching for studies that support or oppose the use of statins in each proposed indication. In some of these emerging indications, a role for statin treatment is more firmly set; for others, current evidence is more controversial. Future trials may reveal more convincing evidence that will make statin use necessary in the therapeutic management of several diseases.