Hormone-receptor positive (HR+), Human-Epidermal-growth Factor negative (HER2-) breast cancer, including the Luminal A and the Luminal B subtypes, is the most common in women diagnosed with ...early-stage BC. Despite the advances in screening, surgery and therapies, recurrence still occurs. Therefore, it is important to identify early those factors that significantly impact the recurrence risk. Based on current evidence and their professional expertise, a Panel of oncologists discussed the definition of high risk of recurrence in early breast cancer. Histological grade, nodal involvement, genomic score, histological grade, tumor size, and Ki-67 proliferation index were rated as the most important factors to define the high risk in patients with early breast cancer. All these factors should be considered comprehensively to tailor the choice of treatment to the peculiar characteristics of each patient.
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•Recurrence still occurs in early HR+ HER2- breast cancer.•Determination of recurrence risk is required to optimize the therapeutic approach.•Histological grade and nodal involvement are the most important factors.•Genomic score, Ki-67, and tumor size are also relevant to define the risk.
In advanced colorectal cancer (ACC), FOLFOX4 has been accepted as a standard chemotherapeutic regimen. Due to the neurotoxicity induced by oxaliplatin, which occurs in about 50% of patients during ...the 6-month FOLFOX4 regimen, and the frequent need for hospitalization, alternative regimens may be required. We aimed to determine whether a 'maintenance' therapy with oral UFT (uracil-tegafur) in patients responding to FOLFOX4 is able to maintain the response and improve the quality of life (QoL) as a result of the outpatient regimen and lower psychological distress.
Untreated patients with ACC who did not progress after 6 months of FOLFOX4 received oral UFT until disease progression or unacceptable toxicity. The aim of the study was to maintain the response obtained with the FOLFOX4 regimen for at least 6 months. The secondary objective was to evaluate QoL during the two different treatment regimens utilizing the 36-item Short Form Health Survey (SF-36).
From January 2003 to August 2004, out of the enrolled 30 patients 22 males and 8 females; 2 patients with a complete response (CR), 14 patients with a partial response (PR) and 6 patients in stable disease (SD) after 6 months of FOLFOX4 22 continued therapy with UFT until progression without significant toxicity; the remaining 8 patients (27%) had progressive disease (PD) during or at the end of FOLFOX4 and were treated with other regimen. After 6 months of UFT, 4 patients (13%) had CR, 6 patients (20%) PR and 4 patients (13%) SD; 16 patients (53%) progressed. Median follow-up was 31 months interquartile range (IQR): 20-31 months; 14 patients died of PD. The median time to progression was 13.9 (IQR: 7.7-20.1) months and the median survival time was 31 months (IQR: 20-31 months). Evaluation of QoL demonstrated a trend towards better QoL during UFT treatment.
These results support the feasibility of maintaining good response and improving QoL (measured by SF-36) with an oral fluoropyrimidine after combination chemotherapy in ACC patients; moreover, since UFT can be used orally, patient compliance is increased and the duration of hospitalization can be decreased.
The development of chemotherapy in the early 1970s resulted in the availability of curative therapeutic strategies for hematological malignancies and several types of solid tumors. It is evident that ...drugs should be used at their optimal dose and schedule, and drug combinations should be given at consistent intervals. According to the mathematical models that suggested the direct dose-response relationship in the improvement of outcomes in cancer chemotherapy, the dose intensity and, more recently, the dose-dense approach was considered one of the most important tools in conventional chemotherapy. Anticancer drugs are often associated with myelotoxicity, and reducing the dose or increasing the time interval between each cycle of treatment is a frequent empiric approach. Unfortunately, a dose reduction of >or=20% causes a loss of 50% in the cure rate, particularly in chemosensitive tumors. To accelerate bone marrow recovery and prevent the onset of severe myelosuppression and its complications, the standard use of granulocyte colony-stimulating factors (G-CSF), such as filgrastim and the long-acting pegfilgrastim, is recommended. The aim of this review is to analyze how dose intensification concepts and dose-dense regimens are able to increase the cure rate of chemosensitive solid tumors and lymphomas.
Coffee is one of the most consumed drinks all over the world. People consume approximately a million bags of coffee in a day. Depending on the drinkers age, amount of consumption, and the like, ...coffee is consumed for its various effects aside from its taste and aroma. Additionally, many people drink coffee because of different factors. The caffeine content of coffee is said to be a stimulant that could make drinkers more alert and awake. However, it could cause negative influences such as disturbance in ones sleeping patterns. Hence, the primary purpose of this correlational research is to determine the relationship between coffee intake and the work performance of coffee-drinking teachers and the implications of coffee intake to them. Survey questionnaires were distributed including teachers coffee intake profiles and observations. Consequently, the students, co-teachers, and administrators of the respondents were also asked to determine the work performance observations of these respondents. The results showed evident implications of the coffee intake manifested by the teachers. Meanwhile, results showed that there were no significant relationships between the coffee intake and the work performance of the respondents. This could be attributed to the respondents long-term coffee consumption leading to their coffee effects tolerance. Recommendations made for teachers are to drink coffee with prudence due to its long-term impact on health. Recommendations were made for future researchers to choose respondents who are new coffee drinkers to ensure that there will be no coffee intake tolerance that could impact the results of the study.
This study describes the antagonistic properties of himbacine, in comparison with those of pirenzepine, at muscarinic receptors mediating the depolarization of rat superior cervical ganglion, the ...inhibition of electrically-induced twitch contractions of rabbit vas deferens and the contraction of dog saphenous vein, currently classified as putative muscarinic M1 sites. The affinity of himbacine for the vas deferens site (pA2 8.08) was nearly ten times higher than those for the M1 receptors of rat ganglion and dog saphenous vein (pA2 7.14 and 7.16, respectively); affinity estimates for pirenzepine were similar throughout the different preparations. The present data are consistent with the allocation of ganglion and saphenous vein receptors into the M1 subclass; the profile of the vas deferens site, conversely, appears to be different, and possibly more closely related to that reported for the M4/m4 receptor.
We have investigated the in vivo motor stimulating and gastroprokinetic properties of the azabicycloalkyl benzimidazolone derivative BIMU 1 ...(3-ethyl-2,3-dihydro-N-(8-methyl-8-azabicyclo3.2.1oct-3-yl)-2-oxo-1H- benzimidazole-1-carboxamide hydrochloride) and its binding profile at 5-hydroxytryptamine3 and 5-hydroxytryptamine4 receptors, in an attempt to assess the serotonergic mechanism underlying its prokinetic action. BIMU 1 dose-dependently (0.01-0.3 mg/kg i.v.) increased the motility of a denervated pouch of canine stomach. This excitatory action was sensitive to muscarinic blockade. A similar stimulatory effect was exerted by the benzamidic prokinetic agent cisapride (0.03-0.3 mg/kg i.v.) but not by the 5-HT3 receptor antagonist ondansetron (up to 1 mg/kg i.v.). The significance for propulsive efficacy of the motor stimulating activity of BIMU 1 was evaluated in a model of gastric emptying of liquids in the conscious dog. The emptying rate of a non-caloric liquid meal instilled through a gastric fistula was accelerated by both BIMU 1 (0.01-1 mg/kg i.v. and 0.1-3 mg/kg p.o.) and cisapride (0.03-1 mg/kg i.v. and 0.3-10 mg/kg p.o.). Ondansetron (1 mg/kg i.v.) did not show any effect. The activity of the 5-HT4 receptor antagonist DAU 6285 was evaluated in the gastric emptying model per se and in interaction experiments on the accelerating action of BIMU 1 (0.3 mg/kg i.v.).
The antiemetic activity of DAU 6215, a novel antagonist of 5-HT3 receptors, was investigated in animal models of cytotoxic treatment-evoked emesis and compared with the antiemetic activity of ...ondansetron and metoclopramide. In dogs, vomiting was induced by i.v. cisplatin; in ferrets, the emetic response was elicited by i.v. doxorubicin or X-ray exposure. Pretreatment with 0.1-1 mg/kg DAU 6215 given i.v. or p.o. prevented the vomiting response to the different emetic agents. In the dog, the antiemetic potency of metoclopramide was 30 times lower than that of DAU 6215. Ondansetron was less potent than DAU 6215 against cisplatin and doxorubicin but was equally effective in the radiotherapy protocol. In this model, lengthening of the pretreatment time to 2 h did not affect the antiemetic efficacy of DAU 6215, whereas it decreased that of ondansetron. The results demonstrate that DAU 6215 is a highly effective and long-lasting inhibitor of cytotoxic treatment-induced emesis in different animal species.
The spasmolytic activity of N-Butyl Hyoscine (NBH) (1) has been investigated in conscious dogs provided with ileal or colonic Thiry fistulas in which motility was stimulated by intraluminal ...distension. In ileal motility experiments, phasic motility index (PMI), intestinal tonus, contraction frequency and heart rate were monitored. Intravenous administration of NBH (10 to 100 micrograms/kg) depressed PMI (ED50 35.1 micrograms/kg) and the other motility parameters. Heart rate increases were observed at 100 micrograms/kg. Application of NBH directly into the fistula (300 to 3000 micrograms/kg) caused a long-lasting, potent inhibition (31-72%) of PMI; tonus and contraction frequency were only slightly affected, while heart rate was not altered. When NBH was administered into an ileal fistula adjacent to the one from which motility was recorded, changes of PMI and other parameters were observed only after a massive dose of the drug (10000 micrograms/kg). In colonic fistula experiments, intraluminal NBH administration (300 to 3000 micrograms/kg) depressed colonic motility (39-59%), without affecting heart rate. It is concluded that NBH present in the intestine, although poorly absorbed, exerts local spasmolytic action.
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