Long-Term Response with Eribulin Mesylate in a Breast Cancer Patient: A Case Report.

Despite the wide pharmacological armamentarium available for the treatment of metastatic breast cancer (MBC), long-lasting control of disease is challenging, especially in heavily pretreated patients. In this case report, we documented a long-lasting complete response (CR) with eribulin in a relatively young woman with MBC and bone metastasis, who did not benefit from prior chemotherapy regimens. Besides CR, the patient was able to maintain an excellent performance status and was free from the severe pain experienced before the initiation of eribulin. Noteworthy, eribulin treatment was very well tolerated, with only a mild alopecia being reported; response was maintained also after a temporary dose interruption and a therapeutic holiday due to non-treatment-related increase in liver enzymes and steatosis.

Therapeutic effect of Streptococcus thermophilus CRL 1190-fermented milk on chronic gastritis.

AIM: To investigate the potential therapeutic effect of exopolysaccharide (EPS)-producing Streptococcus thermophilus (S. thermophilus) CRL 1190 fermented milk on chronic gastritis in Balb/c mice. METHODS: Balb/c mice were fed with the fermented milk for 7 d after inducing gastritis with acetyl-salicylic acid (ASA, 400 mg/kg body weight per day for 10 d). Omeprazole was included in this study as a positive therapeutic control. The gastric inflammatory activity was evaluated from gastric histology and inflammation score, number of interleukin-10 (IL-10), interferon-gamma (INFgamma) and tumor necrosis factor-alpha (TNF-alpha) cytokine-producing cells in the gastric mucosa, and thickness of the mucus layer. RESULTS: Animals receiving treatment with the EPS-producing S. thermophilus CRL 1190 fermented milk showed a conserved gastric mucosa structure similar to that of healthy animals. Inflammation scores of the fermented milk-treated mice were lower than those of mice in the gastritis group (0.2 + or - 0.03 vs 2.0 + or - 0.6, P < 0.05). A marked decrease in INFgamma(+) (15 + or - 1.0 vs 28 + or - 1.2, P < 0.05) and TNF-alpha(+) (16 + or - 3.0 vs 33 + or - 3.0, P < 0.05) cells and an increase in IL-10(+) (28 + or - 1.5 vs 14 + or - 1.3, P < 0.05) cells compared to the gastritis group, was observed. Also, an increase in the thickness of the mucus gel layer (2.2 + or - 0.6 vs 1.0 + or - 0.3; 5.1 + or - 0.8 vs 1.5 + or - 0.4 in the corpus and antrum mucosa, respectively, P < 0.05) compared with the gastritis group was noted. A milk suspension of the purified EPS from S. thermophilus CRL1190 was also effective as therapy for gastritis. CONCLUSION: This study suggests that fermented milk with S. thermophilus CRL 1190 and/or its EPS could be used in novel functional foods as an alternative natural therapy for chronic gastritis induced by ASA.

Participation in clinical trials as viewed by the patient: understanding cultural and emotional aspects which influence choice.

BACKGROUND: Patients invited to take part in a clinical trial may evoke an archetype on which they may base their decision of adherence to participation, instead of on the study itself. METHODS: A 17-item, multiple choice questionnaire was developed, tested and then administered to 102 Italian-speaking patients with advanced lung or breast cancers who had never been exposed to participation in a trial. RESULTS: The questionnaire was answered by all patients. Eighty-five percent were positive about trial participation. Demographic factors did not influence patients' willingness to participate. Trust in the investigator (76%) or in the institute (64%) and hope of receiving a new chance for cure (78%) were cited as reasons to accept participation. A minority was concerned by potential conflicts of interest (31%) or the thought of being 'guinea pigs' (36%), and feared that doctors were interested in advancing their own research, even though there were more efficient drugs available (28%). Fifty percent feared receiving a little-known medicine, and 76% considered that a thorough explanation of toxicity/safety of the proposed treatment helped them decide. CONCLUSION: Several prejudices, fears and some hopes have been captured by the questionnaire. Understanding such specifics will improve patient information leading patients to a more conscious motivation in deciding whether to participate in a clinical trial.

Effects of maternal vitamin B12 deficiency from end of gestation to weaning on the growth and haematological and immunological parameters in mouse dams and offspring.

Vitamin B12-deficiency may induce specific symptoms as neurological alterations and unspecific symptoms such as anaemia and growth retardation. In this study, maternal vitamin B12 deficiency from end of gestation to weaning was evaluated in mouse dams, which was provoked by feeding a vitamin B12-deficient diet. The animals were divided into two groups (control and deficient). The control group received the vitamin B12-deficient diet supplemented with commercial vitamin B12. Compared to the control, the vitamin B12-deficient dams and their offspring showed a significant decrease of body weight (by 20 and 39%, respectively), serum vitamin B12 concentration (by 61 and 67%, respectively), haematological values as haematocrit (25 and 26%, respectively), and IgA producer cells (by 36 and 54%, respectively). In both, vitamin B12-deficient mouse dams and their offspring, histological alterations of small intestine were observed, whereas growth retardation occurred in the offspring only. This experimental murine model allows assessing the incidence of maternal cobalamin deficiency in offspring and would be useful for evaluating novel adjuncts such as functional foods to prevent vitamin B12 deficiency.

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre.

PURPOSE: Fulvestrant ('Faslodex') is an oestrogen receptor (ER) antagonist with no agonist effects. The drug was administered to heavily pre-treated patients with advanced breast cancer (ABC). Patients received Fulvestrant after disease progression (PD) on a previous endocrine treatment or as maintenance treatment after chemotherapy. MATERIAL AND METHODS: Fifty-seven postmenopausal women with ER and/or progesterone receptor-positive ABC resistant to previous endocrine treatments prospectively received fulvestrant 250 mg via intramuscular injection q 28. RESULTS: Twenty-seven patients received fulvestrant after PD and 30 received it as maintenance therapy after chemotherapy. All patients received fulvestrant as second-up to eight-line endocrine treatment for ABC. One patient (2%) had a partial response (PR) and 24 patients (42%) had stable disease > or =12 weeks (SD), including 11 patients who had SD > or =24 weeks. Thirty-two patients (56%) had de novo PD. Clinical benefit (CB; PR + SD > or =24 weeks) occurred in 12 patients (21%). Patients treated as maintenance and treated upon PD had 0 and 4% PR, 43 and 41% SD (including 20 and 19% SD > or =24 weeks), 57 and 55% PD, respectively. Overall, median time to progression (TTP) was 3 months. No differences in CB rate (20% vs. 23%), TTP (3 months vs. 3 months) and time to treatment failure (3 months vs. 3 months) were observed between patients receiving fulvestrant as maintenance therapy and those treated at PD on prior endocrine treatment. No grade 2-4 NCI-CTC toxicity was recorded. CONCLUSIONS: Fulvestrant treatment was associated with prolonged CB and was well tolerated in this group of heavily pre-treated patients with ABC. The outcomes appeared to be similar for patients treated upon PD and those receiving fulvestrant as maintenance therapy.

Primary therapy with ECF in combination with a GnRH analog in premenopausal women with hormone receptor-positive T2-T4 breast cancer.

Patients with hormone receptor-positive tumors less often show a pathological complete response (pCR) than do those with hormone receptor-negative tumors. The addition of endocrine therapies may improve the clinical benefits of primary therapies in these patients. We investigated the efficacy of the epirubicin+cisplatin+fluorouracil (ECF) as continuous infusion) regimen in association with a gonadotropin-releasing hormone (GnRH) analog in 36 premenopausal women with T2-T4a-d N0-2 M0 ER and/or PgR-positive breast cancer. Median age was 39.5 years (range 26-53). Clinical response (complete or partial) was observed in 27 out of 36 patients (75% 95% CI 57.8-87.9%) and a pCR was observed in four patients (11%). Nine (25%) patients had stable disease and no progression was observed. Twenty-one patients (58%) were submitted for breast-conserving surgery and 15 had a radical mastectomy. No baseline clinical and biological characteristics significantly correlated with response. Thirty out of 31 patients evaluable for endocrine assessment had documented ovarian suppression, which occurred after a median of 28 days (range 20-43). We conclude that the combination of ECF and a GnRH analog is associated with a high response rate in the primary treatment of breast cancer. Further studies combining chemotherapy and endocrine agents are warranted in patients with hormone receptor-positive tumors.

Effect of fermented milk containing probiotic bacteria in the prevention of an enteroinvasive Escherichia coli infection in mice.

This study investigated the protective capacity of the oral administration of fermented milk containing the probiotic strains; Lactobacillus casei, Lb. delbrueckii subsp. bulgaricus and Streptococcus thermophilus, against enteroinvasive Escherichia coli infection in a murine (BALB/ c mice) model. Mice were fed for 2, 5 or 7 consecutive days with fermented milk diluted to a concentration of viable Lb. casei, Lb. delbrueckii subsp. bulgaricus and Strep. thermophilus of 10(7) cfu/ml. Phagocytic activity of peritoneal macrophages and the number of IgA+ cells in small and large intestine were determined at the end of the feeding periods. For the preventive effect against Esch. coli, animals were fed for 5 days (selected dose). Mice were challenged with an infective dose of enteroinvasive Esch. coli of 10(8) cfu/mouse. The colonization of liver and spleen and the secretory IgA specific for the pathogen in the intestinal fluid were determined (ELISA test). Results showed that the unspecific immune response enhanced itself after 5 consecutive days of the administration of this fermented milk (increase in the percentage of phagocytosis and number of IgA+ cells in the small intestine). Treated animals showed less Esch. coli colonization of liver than control mice and a higher secretory anti-Esch. coli IgA in the intestinal fluids. These results suggest that the protection against enteroinvasive Esch. coli infection observed for the fermented milk containing probiotic bacteria may be associated with an enhance of the intestinal mucosa immunity.

Adjuvant therapy for very young women with breast cancer: response according to biologic and endocrine features.

Incidence of breast cancer in patients aged < 20 years has been estimated to be 0.1 per 100,000 women. Reported incidences are 1.4 for women aged 20-24 years, 8.1 for women aged 25-29 years, and 24.8 for women aged 30-34 years. Younger patients have been found to have a more aggressive presentation of disease at diagnosis, which is associated with dire prognoses compared with those in premenopausal older patients. Several biologic features might explain the more aggressive behavior of breast cancer in younger patients: higher grade and higher expression of Ki67, higher occurrence of vessel invasion, and less expression of estrogen and progesterone receptors. Choice of adjuvant therapies for women aged <35 years with breast cancer is based on data derived from trials on cohorts of older patients. On average, the effect of chemotherapy for premenopausal patients is substantial: recent evidence suggested that very young women with endocrine-responsive tumors had a higher risk of relapse than older premenopausal patients with similar tumors. This was not the case for patients with endocrine-nonresponsive tumors, for which effects of chemotherapy were similar across ages. Very young women with this disease are faced with personal, family, professional, and quality-of-life issues that further complicate the phase of treatment decision-making. The development of more effective therapies for very young women with breast cancer requires tailored treatment investigations and research focused on issues specific to these patients.

Animal model for in vivo evaluation of cholesterol reduction by lactic Acid bacteria.

For many years, it has been recognized that elevated serum cholesterol is a risk factor associated with atherosclerosis and coronary heart disease, the latter being a major cause of death in Western countries. Numerous drugs that lower cholesterol have been used to treat hypocholesterolemic individuals. However, the undesirable side effects of these compounds have caused concerns about their therapeutic use. Ingestion of probiotic (beneficial for health) lactic acid bacteria (LAB) would possibly be a more natural method to decrease serum cholesterol in humans, as has been was reported. Previous studies have demonstrated that Lactobacillus reuteri administered in low doses has a hypocholesterolemic effect both therapeutically and preventively. One of the key studies in the development of a probiotic is to determine the minimal effective dose of live microorganisms that might be ingested without producing adverse effects (i.e., translocation) in the host. In this chapter, we describe an animal model that allows us to evaluate reduction in hypercholesterolemia by LAB and, also to determine the minimal dose of the microorganism, a critical step in the development of a safe probiotic product.

Interaction of bifidobacteria with the gut and their influence in the immune function.

Bifidobacteria are predominant in the lumen of the large intestine and confer various health benefits on the host. They are also used in the preparation of new fermented milks (bioyogurts) or added to conventional yogurt to generate probiotic effects. The colonization of the gut by bacteria tends to be host specific due partly to the way in which bacteria adhere to the intestinal wall. Using a homologous strain of Bifidobacterium animalis in an experimental mouse model, we analyzed by immunofluorescence labelled-bacteria and transmission electronic microscopy the importance of the bacterial interaction with epithelial an immune cells associated to the gut, and the effect of feeding of B. animalis in the immune response. It was able to adhere and interact with both small and large intestine. In spite of this interaction with the gut, no modifications in the immune state (secretory or systemic response) were observed. A heterologous strain of Bifidobacterium adolescentis from human faeces, was neither incapable of binding to the intestine, nor influence the immune system activation, when it was administered during 2, 5 or 7 consecutive days; we believe that using a homologous strain, oral tolerance is developed even when the microorganism interacts with the immune cells associated with the intestine. However, we cannot ignore the beneficial effect of these microorganisms, especially in the prevention of intestinal infections. We think that this property exerted by bifidobacteria is more related to other mechanisms such as competitive inhibition, acid production or others, than enhancement of the immune state.

Interaction of bifidobacteria with the gut and their influence in the immune function.

Bifidobacteria are predominant in the lumen of the large intestine and confer various health benefits on the host. They are also used in the preparation of new fermented milks (bioyogurts) or added to conventional yogurt to generate probiotic effects. The colonization of the gut by bacteria tends to be host specific due partly to the way in which bacteria adhere to the intestinal wall. Using a homologous strain of Bifidobacterium animalis in an experimental mouse model, we analyzed by immunofluorescence labelled-bacteria and transmission electronic microscopy the importance of the bacterial interaction with epithelial an immune cells associated to the gut, and the effect of feeding of B. animalis in the immune response. It was able to adhere and interact with both small and large intestine. In spite of this interaction with the gut, no modifications in the immune state (secretory or systemic response) were observed. A heterologous strain of Bifidobacterium adolescentis from human faeces, was neither incapable of binding to the intestine, nor influence the immune system activation, when it was administered during 2, 5 or 7 consecutive days; we believe that using a homologous strain, oral tolerance is developed even when the microorganism interacts with the immune cells associated with the intestine. However, we cannot ignore the beneficial effect of these microorganisms, especially in the prevention of intestinal infections. We think that this property exerted by bifidobacteria is more related to other mechanisms such as competitive inhibition, acid production or others, than enhancement of the immune state.

Effect of a Mixture of Lactobacillus casei and Lactobacillus acidophilus Administered Orally on the Immune System in Mice.

The effects of an orally-administered mixture of Lactobacillus casei and Lactobacillus acidophilus on the immune system in Swiss albino mice were studied. Non-fermented milk containing viable cultures of both microorganisms was fed for different consecutive days to the animals, the effect of such feeding on their immune system was evinced by macrophage and lymphocyte activation. An increase both in the in vitro phagocytic activity of peritoneal macrophages and in the carbon clearance activity was observed. As regard the lymphocytic activity, the mixture produced a higher activation than that in the control mice. The enhanced macrophage and lymphocytic activity by administering cultures via the oral route, suggest the advisability of using the mixture of bacteria for a more efficient stimulation of the host immune response.