Respiratory and muscular response to acute non-metabolic fatigue during ramp incremental cycling.

We tested the hypothesis that acute, non-metabolic fatigue, by reducing maximal power output and possibly increasing muscle recruitment at a given exercise intensity, will reduce indexes of exercise tolerance during incremental cycling. Ten subjects performed three ramp incremental tests respectively after static stretching (STRC), dropjumps (DJ) or control (CTRL). Fatigue was assessed as reduction in maximal power output (sprintPO) during isokinetic sprints. During the ramps we measured: oxygen consumption (VO2), power output (PO), and surface electromyography. sprintPO was reduced after STRC and DJ (p = 0.007) yet not after CTRL. During the ramps, the interventions augmented muscle excitation vs CTRL (p ≤ 0.001). Peak PO and VO2 were reduced after STRC (302 ±â€¯39W p = 0.033, 3365 ±â€¯465 ml/min p = 0.015) and DJ (300 ±â€¯37W p = 0.023, 3413 ±â€¯476 ml/min p = 0.094) vs CTRL (314 ±â€¯41W, 3505 ±â€¯486 ml/min). Interventions were associated with early occurrence of the ventilatory thresholds and increased VO2 vs CTRL (p = 0.029). The physiological response after acute non-metabolic fatigue suggests a link between exercise intolerance and the decreased ability to produce force.

Focus on genetic and epigenetic events of colorectal cancer pathogenesis: implications for molecular diagnosis.

Originally, colorectal cancer (CRC) tumorigenesis was understood as a multistep process that involved accumulation of tumor suppressor genes and oncogenes mutations, such as APC, TP53 and KRAS. However, this assumption proposed a relatively limited repertoire of genetic alterations. In the last decade, there have been major advances in knowledge of multiple molecular pathways involved in CRC pathogenesis, particularly regarding cytogenetic and epigenetic events. Microsatellite instability, chromosomal instability and CpG island methylator phenotype are the most analyzed cytogenetic changes, while DNA methylation, modifications in histone proteins and microRNAs (miRNAs) were analyzed in the field of epigenetic alterations. Therefore, CRC development results from interactions at many levels between genetic and epigenetic amendments. Furthermore, hereditary cancer syndrome and individual or environmental risk factors should not be ignored. The difficulties in this setting are addressed to understand the molecular basis of individual susceptibility to CRC and to determine the roles of genetic and epigenetic alterations, in order to yield more effective prevention strategies in CRC patients and directing their treatment. This review summarizes the most investigated biomolecular pathways involved in CRC pathogenesis, their role as biomarkers for early CRC diagnosis and their possible use to stratify susceptible patients into appropriate screening or surveillance programs.

Efficacy and safety analysis of once per cycle pegfilgrastim and daily lenograstim in patients with breast cancer receiving adjuvant myelosuppressive chemotherapy FEC 100: a pilot study.

BACKGROUND: Neutropenia is a common toxicity in patients receiving myelosuppressive chemotherapy. In this prospective pilot study, we compared the efficacy and safety profiles of pegfilgrastim administered subcutaneously once per cycle and lenograstim administered subcutaneously daily six times per cycle, for primary neutropenia prophylaxis in women with breast cancer receiving adjuvant anthracycline-based chemotherapy. MATERIALS AND METHODS: Twenty women were enrolled. All patients received epirubicin 100 mg/m(2) with 5-fluorouracil 500 mg/m(2) and cyclophosphamide 500 mg/m(2) on day 1 and every 21 days thereafter, according to the FEC 100 chemotherapy regimen. Eight patients received a single dose of pegfilgrastim on day 2, while 12 patients were treated with daily administration of lenograstim from days five to ten. Absolute neutrophil count and duration of grade 3-4 neutropenia were monitored using seriated blood samples. The incidence of bone pain was evaluated using the visual analog scale (VAS). RESULTS: The incidence of grade 3-4 neutropenia was 75% in patients who received pegfilgrastim, and 25% in patients who received lenograstim. One case of febrile neutropenia was shown in pegfilgrastim patients. The mean duration of grade 3-4 neutropenia was 2 days in pegfilgrastim group versus 1.4 days in the lenograstim group. Bone pain was present in 37.5% of pegfilgrastim patients versus 58.3% of lenograstim patients. The mean duration of bone pain in the pegfilgrastim group was 4 days versus 6 days in the lenograstim group. CONCLUSION: In our experience, a single injection of pegfilgrastim was less effective for controlling neutropenia than six daily injections of lenograstim. The safety profiles of pegfilgrastim and lenograstim were similar with a lower incidence of bone pain in patients treated with pegfilgrastim.

A 68-year-old Caucasian man presenting with urinary bladder lymphoepithelioma: a case report.

INTRODUCTION: Lymphoepithelioma is a very rare form of malignant tumor originating from epithelial line cells. Its occurrence has potential clinical, therapeutic and prognostic implications. In the present report we describe an unusual case of bladder cancer with two different histological varieties: transition cell carcinoma and lymphoepithelioma-like carcinoma. Lymphoepithelioma-like carcinoma of the bladder has only been rarely reported in the literature to date. CASE PRESENTATION: We present the case of a 68-year-old Caucasian man who, after occurrence of hematuria, underwent transurethral resection of a bladder tumor. The results of a histological examination confirmed a high-grade non-muscle-invasive pT1 lymphoepithelioma-like carcinoma of the urinary bladder, associated with a concurrent high-grade transition cell carcinoma. After analyzing the histological features, our patient was subjected to treatment with intra-vesical instillations of bacillus Calmette-Guérin. Our work stresses that diagnosis and therapeutic approaches can be difficult and controversial, especially in the early stages of this rare carcinoma. CONCLUSIONS: This report emphasizes the importance of extending our knowledge and experiences regarding this uncommon carcinoma. Further studies are needed to better understand this rare disease and define more accurate diagnostic and therapeutic strategies.

Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC).

Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features.