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24 result(s) for "Susini, Tommaso"
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Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16
Invasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women’s health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER − /PR − /HER2 + , and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44 + /CD24 −/low ), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p -adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within − 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.
Steroidal and non-steroidal third-generation aromatase inhibitors induce pain-like symptoms via TRPA1
Use of aromatase inhibitors (AIs), exemestane, letrozole and anastrozole, for breast cancer therapy is associated with severe pain symptoms, the underlying mechanism of which is unknown. The electrophilic nature of AIs suggests that they may target the transient receptor potential ankyrin 1 (TRPA1) channel, a major pathway in pain transmission and neurogenic inflammation. AIs evoke TRPA1-mediated calcium response and current in rodent nociceptors and human cells expressing the recombinant channel. In mice, AIs produce acute nociception, which is exaggerated by pre-exposure to proalgesic stimuli, and, by releasing sensory neuropeptides, neurogenic inflammation in peripheral tissues. AIs also evoke mechanical allodynia and decreased grip strength, which do not undergo desensitization on prolonged AI administration. These effects are markedly attenuated by TRPA1 pharmacological blockade or in TRPA1-deficient mice. TRPA1 is a major mediator of the proinflammatory/proalgesic actions of AIs, thus suggesting TRPA1 antagonists for the treatment of pain symptoms associated with AI use. Use of aromatase inhibitors for breast cancer therapy is associated with severe pain symptoms, the underlying mechanism of which is unknown. Here the authors show that in mice, TRPA1 is a major mediator of the proinflammatory and proalgesic actions of aromatase inhibitors.
Medicines for headache before and during pregnancy: a retrospective cohort study (ATENA study)
ObjectiveTo investigate headache treatment before and during pregnancy.BackgroundMost headaches in pregnancy are primary disorders. Headaches are likely to ameliorate during pregnancy, although they may also begin or worsen. Most headache medications should be avoided during pregnancy because of potential fetal risks. However, only scarce evidence on headache drug consumption during pregnancy is available.DesignATENA was a retrospective, self-administered questionnaire-based, cohort study on women in either pregnancy or who have just delivered and reporting headache before and/or during pregnancy.ResultsOut of 271 women in either pregnancy or who have just delivered, 100 (37%) reported headache before and/or during pregnancy and constituted our study sample. Before pregnancy, the attitude toward the use of symptomatic drugs was characterized by both a strong focus on their safety and the willingness to avoid possible dependence from them. Compared to the year before, pregnancy led to changes in behavior and therapeutic habits as shown by a higher proportion of patients looking for information about drugs (44/100 [44%] vs. 36/100 [36%]) and a lower proportion of those treating headache attacks (88/100 [88%] vs. 52/100 [52%]) and by a lower use of nonsteroidal anti-inflammatory drugs (68/100 [68%] vs. 5/100 [5%]) and a much higher use of paracetamol (33/100 [33%] vs. 95/100 [95%]).ConclusionsPregnancy changes how women self-treat their headache, and leads to search for information regarding drug safety, mostly due to the perception of fetal risk of drugs. Healthcare providers have to be ready to face particular needs of pregnant women with headache.
FGD3 Gene as a New Prognostic Factor in Breast Cancer
Despite the establishment of the traditional prognostic factors for breast cancer, patients belonging to the same histological and molecular subgroup often present quite different outcomes. Recently, the introduction of gene expression profiling, assessed by RT-qPCR and microarray DNA analysis, offered a view of the whole cell gene activity and the ability to identify new transcripts that are associated with outcome. This review aimed to gather all recent trials about new breast cancer prognostic factors, focusing on the most promising one, the FGD3 gene, and to discuss the real feasibility of a molecular approach in everyday clinical practice. In conclusion, all literature concerning this subject indicated that expression of the FGD3 gene is a strong marker of good prognosis in breast cancer patients and that immunohistochemistry represents an efficient, inexpensive, reproducible evaluation method, affordable also by small Institutions.
Breast Cancer Risk and Prevention: A Step Forward
Breast cancer (BC) is a leading topic in medical research as it is the most common cancer occurring in women worldwide; its incidence is progressively increasing in all age groups [...].Breast cancer (BC) is a leading topic in medical research as it is the most common cancer occurring in women worldwide; its incidence is progressively increasing in all age groups [...].
Role of axillary ultrasound examination in the selection of breast cancer patients for sentinel node biopsy
Sentinel node biopsy (SNB) is a time-consuming procedure that can be avoided in presence of axillary metastases. The aim of this study was to assess the accuracy of ultrasound scan (US) in the prediction of axillary nodes status in patients scheduled for SNB. Axillary US was performed and when feasible, a core biopsy of suspicious nodes was taken. The nodal status as assessed by US and/or core biopsy was compared with final histology. Of the 132 patients enrolled, 31 (23.5%) had suspicious axillary nodes according to US; 19 (61.3%) were true positive, whereas 12 cases (38.7%) were not. In 14 of 31 suspicious cases an US-guided core-biopsy was taken, which in 11 of 14 cases (78.5%) confirmed the neoplastic involvement. Overall, core biopsy of the nodes correctly predicted the final histology in 13 of 14 cases (92.8%). The US of axillary nodes, possibly associated with core biopsy, improved the preoperative evaluation of breast cancer patients scheduled for SNB.
Nuclear Expression of β-Catenin Is Associated with Improved Outcomes in Endometrial Cancer
Beta-catenin is involved in intercellular adhesion and participates in the Wnt signaling pathway. This study evaluated the expression pattern and prognostic value of β-catenin in a series of endometrial carcinoma patients. Immunohistochemical analyses were used to assess the expression and subcellular localization of β-catenin from tissue sections of 74 patients with endometrial carcinoma. No correlation was found between beta-catenin expression and clinicopathological parameters. Patients expressing nuclear β-catenin (n = 13; 16%) showed a more favorable prognosis than patients expressing membranous β-catenin; the 5-year disease-related survival rate was 100% for cases expressing nuclear β-catenin, compared with 73.8% (SE 0.08) of cases expressing membranous β-catenin (p = 0.04). Although statistical significance was not reached (p = 0.15), cases expressing nuclear β-catenin showed a 5-year disease-free survival rate of 90.9% (SE 0.08) compared with 67.4% (SE 0.08) of cases expressing membranous β-catenin. Univariate Cox analysis revealed that membranous β-catenin expression was found to be associated with a relative risk of death of 33.9 (p = 0.04). The stage of disease (p = 0.0006), histology (p = 0.003), and grading (p = 0.008) were also significantly correlated with disease-free survival according to univariate Cox analyses. Determining β-catenin expression and localization patterns may predict survival in patients with endometrial cancer and, therefore, should be considered a potential prognostic marker of disease.
Relationship between cervical dilation and time to delivery in women with preterm labor
Background: Early recognition of the signs and symptoms of preterm labor (PTL) is important in order to establish treatment. Our aim was to determine the relation between cervical dilatation and time interval from admission to delivery in women with preterm labor. Materials and Methods: A retrospective cohort study was conducted on 83 singleton gestations admitted for preterm labor between 24 weeks and 34 weeks, who subsequently delivered preterm. Women were categorized into three groups of cervical dilatation (0-2 cm, 3-6 cm, >6 cm) and the time interval from admission to delivery was compared. Cox regression analysis was performed to assess the association between cervical dilatation and time interval from admission to delivery. The other variables examined were gestational age (GA) at admission and length of the cervix, when performed. Results: The time interval from admission to delivery was significantly shorter in women with higher dilatation of the cervix (p < 0.02) and in those admitted at a more advanced gestational age (p < 0.05). Forty-eight percent of women with cervical dilatation 0-2 cm delivered in the first 48 h compared to 85% of the women with a dilatation of 3-6 cm. No significant association was found between the length of the cervix and the time interval to delivery. Conclusion: Dilatation of the cervix and gestational age at admission are associated with the time interval to delivery in women with preterm labor. The assessment of the length of the cervix is unlikely to add clinical information in women with an already dilated cervix.
Reducing the Use of Frozen Section for Sentinel Node Biopsy in Breast Carcinoma: Feasibility and Outcome
Sentinel lymph node biopsy (SLNB) is a standard practice for staging the axilla in breast cancer. Initially, intraoperative frozen section (FS) examination was used but was time-consuming and often provided false-negative results. Delayed permanent section (PS) analysis is currently performed; FS-SLNB is maintained for selected high-risk cases. The aim of this study was to evaluate the feasibility of this approach. All patients with breast cancer with clinically negative lymph nodes undergoing SLNB at our institution from 2004 to 2020 were analyzed, comparing operative time, re-operation rate and clinical outcome in terms of regional lymphatic recurrence-free and overall survival by type of SLNB (FS vs. PS). FS-SLNB comprised 100% of the procedures in 2004 and 18.2% at the end of the study period. The use of PS-SLNB instead of FS-SLNB was associated with a significantly reduced rate of axillary dissection (AD): 4.4% vs. 27.2, respectively (p<0.001). There was no significant difference in re-operation rate for AD: 3.9% vs. 6.9%, respectively (p=0.20). The use of PS-SLNB significantly reduced the operative time (mean=51 minutes) (p<0.001). After a mean follow-up of 70.9 months (range=16-180 months) there were no differences in regional lymphatic recurrence free or overall survival. The reduced use of FS-SLNB resulted in a significantly lower rate of AD, and significant operative time and costs savings, without any increase in the reoperation rate and lymphatic recurrences. Therefore, this approach is feasible, safe and beneficial, both for patients and healthcare services.
Expression of FGD3 gene as prognostic factor in young breast cancer patients
The FGD3 gene works as a cell migration inhibitor and seems to be a promising indicator of outcome in some human cancers including breast. In this study, we analysed for the first time the prognostic role of FGD3 in young breast cancer patients. We studied the relationship between traditional prognostic factors, FGD3 expression and outcome in ≤40 years breast cancer patients. We found that lower FGD3 expression decreased the probability of disease-free survival ( p  = 0.042) and overall survival ( p  = 0.007). In a multivariate analysis for overall survival AJCC stage ( p  = 0.005) and FGD3 expression ( p  = 0.03) resulted independent prognostic factors. Low FGD3 expression increased the risk of death from disease (HR 5.73, p  = 0.03). Moreover, low FGD3 expression was associated with more widespread lymph node involvement ( p  = 0.04) and a lower FGD3 staining intensity was found in positive-lymph-node patients vs negative ( p  = 0.003) and in patients with ≥10 involved lymph nodes vs <10 ( p  = 0.05). Our results suggest FGD3 to be a significant independent prognostic factor in young breast cancer patients in terms of disease-free survival and overall survival. A lower expression increased the risk of recurrence and death from disease and was associated with widespread lymph node metastases.