1,720,979 research outputs found
Overcoming treatment resistance in HER2-positive breast cancer: potential strategies.
Full text linkHuman epidermal growth factor receptor (HER)-2 overexpression or amplification occurs in about 20% of all breast cancers and results in a worse prognosis. Nevertheless, anti-HER2 treatments have recently been developed, resulting in dramatic improvements in the clinical outcome of patients with HER2-positive breast cancer. Trastuzumab has shown efficacy in early and advanced breast cancer treatment and lapatinib is currently approved for the treatment of advanced disease. Other anti-HER2 agents are being investigated. Mechanisms of resistance to trastuzumab treatment include crosstalk with heterologous receptors and amplification of HER2 signalling; amplification of the phosphoinositide 3-kinase (PI3K)/AKT pathway; alteration in binding of trastuzumab to HER2; and loss of HER2 expression. Proposed mechanisms of resistance to lapatinib involve derepression and/or activation of compensatory survival pathways through increased PI3K/AKT or estrogen receptor (ER) signalling. Several strategies to overcome resistance to anti-HER2 treatment are in different phases of development and include treatment with pertuzumab, T-DM1 and mammalian target of rapamycin (mTOR) inhibitors
Pegylated liposomal doxorubicin in elderly patients with metastatic breast cancer
No full textBreast cancer incidence is increasing among elderly patients. Age is a risk factor for toxicity after chemotherapy for breast cancer. In particular, anthracycline-induced cardiac toxicity is increased in elderly patients. Novel liposomal anthracyclines are associated with less cardiotoxicity. Pegylated liposomal doxorubicin (PLD) is active in breast cancer patients and, has shown comparable efficacy to conventional doxorubicin in clinical trials. Most toxicities during PLD treatment are hematological and mucocutaneous (in particular stomatitis and palmo-plantar erythrodysesthesia), and cardiac toxicity is rare. Tolerability of this agent in elderly patients has been confirmed by clinical trials in the advanced disease. Due to its efficacy and safety profile, PLD is an appealing treatment option for elderly breast cancer patient
Twelve years of endoscopic surveillance in a family carrying biallelic Y165C MYH defect: Report of a case
No full textPURPOSE: We report the case of two siblings, clinically and endoscopically followed for 12 years, who displayed an attenuated adenomatous polyposis coli phenotype. METHODS: On workup for rectal bleeding with colonoscopy, we found multiple adenomas mainly right- sided in a 21-year-old female and the same colonic phenotype was observed in her 27-year-old brother. We made a clinical diagnosis of attenuated adenomatous polyposis coli and performed APC gene testing. Because they had refused the proposed ileorectal anastomosis surgical option, we planned a periodic, endoscopic follow- up. RESULTS: Gene testing did not confirm the clinical suspicion of attenuated adenomatous polyposis coli. Actually, we did not find any pathogenic mutation in APC gene and we recently identified a biallelic Y125C MYH defect. During the endoscopic follow- up, a progressive reduction of adenomas was seen. CONCLUSIONS: New insight colorectal cancer genetics have allowed definition of a new class of polyposis that applies to some patients with attenuated adenomatous polyposis coli phenotype as in the siblings we have described. To prevent colorectal cancer without recurring to surgery, colonoscopic polypectomy may be a suitable tool in controlling MYH polyposis
Markers of the uPA system and common prognostic factors in breast cancer
No full textThe urokinase plasminogen activator (uPA) system includes uPA and plasminogen activator inhibitor types 1 (PAI-1) and 2 that mainly act by regulating extracellular matrix degradation, and it is involved in tumor progression. The -675 4G/5G polymorphism of the PAI-1 gene regulates PAI-1 activity in serum. We aimed at studying the -675 4G/5G polymorphism of the PAI-1 gene and uPA, PAI-1, and cyclooxygenase-2 (COX-2) immunohistochemical expression in a series of breast cancer cases. Homozygosity for the 4G allele of the PAI-1 gene was associated with node-positive breast cancer ( P = .02). We showed a direct correlation between uPA and estrogen receptor expression ( P = .03); negative uPA expression was associated with negative hormonal expression, high tumor grade, and high proliferation index ( P < .05). A direct correlation was seen between uPA and PAI-1, uPA and COX-2, and PAI-1 and COX-2 expression ( P < .05). Interaction between uPA and COX-2 systems in breast cancer deserves further study
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Determinants of recovery from amenorrhea in premenopausal breast cancer patients receiving adjuvant chemotherapy in the taxane era.
No full textChemotherapy-induced amenorrhea occurs in about 20-70% of premenopausal breast cancer patients. Chemotherapy-induced amenorrhea can affect choice of hormonal therapy, fertility, and quality of life of breast cancer survivors. We retrospectively analyzed the incidence of amenorrhea after adjuvant chemotherapy and the subsequent recovery of the menses in 145 breast cancer patients. Age, smoking, alcohol consumption, body mass index, chemotherapy regimen, previous hormonal therapies, and previous childbearing were analyzed as potential predictive factors of ovarian function recovery. Median age was 42 years at the beginning of adjuvant chemotherapy with 30.3% of patients below 40 years of age. The majority (87.6%) of patients received anthracycline-based chemotherapy, 35.2% of patients received a cyclophosphamide-methotrexate-5-fluorouracil regimen and 42.8% received a taxane. The incidence of chemotherapy-induced amenorrhea was 80, and 35.3% of these patients resumed menses after a median of 8 months. In multivariate analysis, younger age (<40 years, P=0.01) and taxane-based chemotherapy (P=0.03) were associated with increased probability of recovery of menses after chemotherapy-induced amenorrhea. In contrast, cyclophosphamide-methotrexate-5-fluorouracilbased chemotherapy (P=0.07) and previous childbearing (P=0.04) were associated with an increased probability of permanent chemotherapy-induced amenorrhea. Recovery of menses after chemotherapy-induced amenorrhea occurs more probably in younger women, with no pregnancies and receiving taxane
Balance between cell division and cell death as predictor of survival in patients with non-small-cell lung cancer
No full textOBJECTIVE:
To evaluate the prognostic value of the balance between apoptosis and proliferation in non-small-cell lung cancer (NSCLC).
METHODS:
Paraffin-embedded sections from a consecutive series of radically resected NSCLCs were scored for apoptosis (in situ DNA nick end labeling assay) and proliferation (immunohistochemistry for MIB-1). A total of 1,000 cells were counted per case, to obtain apoptotic (AI) and MIB-1 indices. Other potential prognostic indicators (pT, pN, pStage and histology) and p53 status were also evaluated.
RESULTS:
Univariate analysis showed that adenocarcinomatous histotype (p = 0.03), nodal involvement (p = 0.04), higher pStage (p = 0.001) and the combination of low AI and high MIB-1 expression (p = 0.03) were associated with poorer outcome. The significant prognostic value of the combination 'low AI/high MIB-1' was also confirmed in a multivariate analysis after adjustment for other covariates.
CONCLUSION:
These results underline the importance of considering apoptosis and proliferation together to identify a subgroup of NSCLC associated with poor survival
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