The recent successful development of monoclonal antibodies that target key components of biological pathways has expanded the armamentarium of treatment options for patients with colorectal cancer ...(CRC). In particular, the epidermal growth factor receptor (EGFR), a tyrosine kinase growth factor receptor involved in CRC development and progression, is exploited by the newest monoclonal antibody that is available for use in CRC patients. Cetuximab, the first chimeric monoclonal antibody, which has been generated against the EGFR, is currently registered in USA, Europe and worldwide, in combination with irinotecan in the treatment of metastatic CRC patients who have progressed on irinotecan containing chemotherapy. Cetuximab is well tolerated and does not exacerbate the toxicity of concomitant chemotherapy. Furthermore, a series of phase III clinical trials are currently evaluating the combination of cetuximab with standard chemotherapy regimens in the first-line treatment chemotherapy-naïve patients with metastatic CRC.
The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks ...(FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m(-2) on day 1, FA 200 mg m(-2) as a 2 h infusion followed by bolus 5-FU 400 mg m(-2) and a 22 h infusion of 5-FU 600 mg m(-2), repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer.
Background The elderly are characterized by a high prevalence of chronic heart failure (CHF) and frailty, which is a complex interaction of physical, psychological and social impairment. This study ...aimed to examine the predictive role of frailty on long‐term mortality in elderly subjects with CHF.
Materials and methods The study assessed long‐term mortality after 12‐year follow up in 120 subjects with CHF and 1139 subjects without CHF, selected in 1992, from a random sample of the elderly population in the Campania region of Italy. Frailty was assessed according to a ‘Frailty Staging System’.
Results Subjects with CHF were prevalently female (60%) and older than 75 years (mean 75·9 ± 6·7); subjects without CHF were prevalently female (56·4%) and younger than 75 years (mean 74·0 ± 6·3). In subjects with and without CHF stratified into classes of frailty there was a statistically significant increase in age, comorbidity, disability and low social support, and a decrease in MMSE score. Moreover, death progressively increased more with frailty in subjects (70·0% to 94·4%, P < 0·03) than in those without (43·8.% to 88·3%, P < 0·0001) CHF. The Kaplan–Meier analysis shows that at 9 years the probability of survival progressively decreased as frailty increased (45·5% to 0%) in subjects with CHF and from 62·8% to 25·9% in subjects without CHF. The Cox regression analysis indicated that frailty is predictive of mortality in the multivariate model adjusted for several variables including sex and age in subjects with and without CHF. Moreover, the analysis showed that frailty is more predictive of mortality in elderly subjects with CHF when it was analyzed either as continuous (1·48 vs. 1·36) or as a dummy (3 vs. 1 = 1·62 vs. 1·24) variable.
Conclusions Thus mortality among elderly subjects with or without CHF increases with frailty. Moreover, frailty is more predictive of long‐term mortality in elderly subjects with than in those without CHF. Hence, frailty represents a new independent variable for predicting long‐term mortality in elderly subjects with CHF.
We present a digital atlas of the glomeruli in the antennal lobe of the honeybee, Apis mellifera, accessible to the scientific community via the Internet. The atlas allows the identification of ...glomeruli in preparations in which the glomeruli can be recognized, be it in sections or in whole-mounts. The high resolution of the anatomical data upon which the atlas is based and its electronic form should prove to be an important tool for anyone involved in the study of the honeybee antennal lobe. Its accessibility via the Internet is a step towards interactive and freely accessible databases of animal brains.
The insect antennal lobe is the first brain structure to process olfactory information. Like the vertebrate olfactory bulb the antennal lobe is substructured in olfactory glomeruli. In insects, ...glomeruli can be morphologically identified, and have characteristic olfactory response profiles. Local neurons interconnect glomeruli, and output (projection) neurons project to higher-order brain centres. The relationship between their elaborate morphology and their physiology is not understood. We recorded electrophysiologically from antennal lobe neurons, and iontophoretically injected a calcium-sensitive dye. We then measured their spatio-temporal calcium responses to a variety of odours. Finally, we confocally reconstructed the neurons, and identified the innervated glomeruli. An increase or decrease in spiking frequency corresponded to an intracellular calcium increase or decrease in the cell. While intracellular recordings generally lasted between 10 and 30 min, calcium imaging was stable for up to 2 h, allowing a more detailed physiological analysis. The responses indicate that heterogeneous local neurons get input in the glomerulus in which they branch most strongly. In many cases, the physiological response properties of the cells corresponded to the known response profile of the innervated glomerulus. In other words, the large variety of response profiles generally found when comparing antennal lobe neurons is reduced to a more predictable response profile when the innervated glomerulus is known.
Honeybees can be trained to associate odorants to sucrose reward by conditioning the proboscis extension response. Using this paradigm, we have recently shown that bees can solve a side-specific ...task: they learn simultaneously to discriminate a reinforced odor A from a non-reinforced odor B at one antenna (A+B−) and the reversed problem at the other antenna (A−B+). Side-specific (A+B−/B+A−) conditioning is an interesting tool to measure neurophysiological changes due to olfactory learning because the same odorant is excitatory (CS+) on one brain side and inhibitory (CS−) on the opposite side. In the bee brain, the antennal lobe (AL) is the first olfactory relay where the olfactory memory is established. Using calcium imaging, we compared odor-evoked activity in the functional units, the glomeruli, of the two ALs, both in naive and conditioned individuals. Each odor evoked a different pattern of glomerular activity, which was symmetrical between sides and highly conserved among naive animals. In conditioned bees, response patterns were overall symmetrical but showed more active glomeruli and topical differences between sides. By representing odor vectors in a virtual olfactory space whose dimensions are the responses of 23 identified glomeruli, we found that distances between odor representations on each brain side were significantly higher in conditioned than in naive bees, but only for CS+ and CS−. However, the distance between CS+ and CS− representations was equal to that of naive individuals. Our work suggests that side-specific conditioning decorrelates odor representations between AL sides but not between CS+ and CS− within one AL.
It is reported that odorants delivered naturally to the honeybee evoked specific spatio-temporal excitation patterns in the antennal lobe, the structural and functional analogue of the olfactory ...bulb. A comparison between different individuals shows remarkable similarities for a pheromone component, but not for general flower odors.
Background: This randomized, multicenter, phase III trial evaluated the efficacy and safety of the combination of epirubicin, leucovorin, 5-fluorouracil and etoposide (ELFE regimen) as adjuvant ...therapy for radically resected gastric cancer patients. Patients and methods: From June 1996 to June 2001, 228 stage IB–IIIB gastric cancer patients were enrolled. All patients received a total or subtotal gastrectomy with at least a D1 lymphoadenectomy and were randomly assigned to receive surgery alone or surgery followed by chemotherapy. Results: A total number of 630 cycles was delivered with a median number of 5. With a median follow-up of 60 months, the 5-year overall survival (OS) was 48% in the treatment arm and 43.5% in the control arm hazard ratio (HR) 0.91; 95% confidence interval (CI) 0.69–1.21; P = 0.610); the 5-year disease-free survival (DFS) was 44% in the treatment arm and 39% in the control arm (HR 0.88; 95% CI 0.78–0.91; P = 0.305). In node-positive patients, the 5-year OS was 41% in the treatment arm and 34% in the control arm (HR 0.84; 95% CI 0.69–1.01; P = 0.068), while the 5-year DFS was 39% in the treatment arm and 31% in the control arm (HR 0.88; 95% CI 0.78–0.91; P = 0.051). The most common grade 3–4 toxic effects according to World Health Organization criteria were hematological and gastrointestinal. Conclusions: In radically resected gastric cancer patients, adjuvant chemotherapy with ELFE regimen does not improve OS over surgery alone.
Purpose: Conventional staging procedures are often unable to precisely predict prognosis in colorectal cancer (CRC). In this study,
we set out to investigate the possible role of molecular/structural ...indicators involved in cell cycle regulation (p27 and
p53), apoptosis (p53 and p27), and tumor neoangiogenesis p53, vascular endothelial growth factor (VEGF), and microvessel
count in predicting tumor behavior and clinical outcome in CRC patients
Experimental Design: Analysis of the above indicators was performed by immunohistochemistry on 104 CRC patient samples and 25 normal colon mucosa
specimens.
Results: Intense p27 nuclear staining was found in normal colon mucosa, with p53 nuclear staining and VEGF cytoplasmic accumulation
<10%, and low microvessel count. In contrast, in CRC samples, p27 was down-regulated in 53.8%, p53 protein was overexpressed
in 52%, and VEGF stained positive in 67.3% of the cases, respectively. Multiple regression analysis showed that molecular
markers were strongly correlated. In patients treated with curative surgery, a significant relationship was seen between p27
down-regulation and Dukes’ stage, nodal status, and the presence of distant metastases. VEGF overexpression correlated significantly
with Dukes’ stage, tumor ( t ) and metastasis ( m ) parameters, and left site. Stepwise regression selected p27, p53, VEGF, and Dukes’ stage as the best combination of variables
capable of predicting both disease-specific and disease-free survival.
Conclusions: The investigated indicators may be useful for the prediction of outcome and recurrence rate in curatively treated CRC patients.
In conjunction with clinical and pathological staging, they may provide a stronger indication of clinical outcome than staging
alone and help better select therapeutic options in CRC patients.
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