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Alfredo A Santillan

Publications and source records attributed to Alfredo A Santillan.

8 recordsLinked to original sources
PubMed2025

MammaPrint predicts chemotherapy benefit in HR+HER2- early breast cancer: FLEX Registry real-world data.

BACKGROUND: Gene expression assays help personalize adjuvant chemotherapy decisions for hormone receptor-positive, HER2-negative (HR+HER2-) early breast cancer (EBC). The 70-gene risk of distant-recurrence signature, MammaPrint, demonstrated clinical utility in guiding chemotherapy de-escalation in genomically low risk patients in the MINDACT trial. This study evaluates MammaPrint as a continuous predictor of chemotherapy benefit in HR+HER2- EBC using real-world data (RWD) from the FLEX Registry. METHODS: The study evaluated 1002 patients treated with endocrine therapy (ET) only or ET with chemotherapy (ET+CT) enrolled in FLEX (NCT03053193) with 5-year median follow-up. Propensity-score matching balanced treatment groups by menopausal status, T-stage, and nodal status. The primary endpoint was distant recurrence-free interval (DRFI). Regression and Cox proportional hazards models assessed chemotherapy benefit across MammaPrint Index (MPI) risk. RESULTS: Most patients were postmenopausal (70.1%), node-negative (70.0%), and had grade 2 tumors (51.2%). The regression models showed that MPI strongly predicted 5-year DRFI in ET only (R2 = 0.99, P&#x2009;<&#x2009;.001) and ET + CT (R2 = 0.90, P&#x2009;<&#x2009;.001) groups, corresponding to an average absolute chemotherapy benefit of 5.6% in High 1 and 10.9% in High 2. Minimal improvement in DRFI with chemotherapy was observed for Low (1.7%) and UltraLow (<1.0%) risk groups. A multivariate Cox model with an MPI-by-treatment interaction term demonstrated that increasing MPI risk was associated with greater chemotherapy benefit on DRFI (HR&#x2009;=&#x2009;0.15, P&#x2009;=&#x2009;.047). Chemotherapy benefit was significantly associated with premenopausal status, but not age, T-stage, nodal status, or grade. CONCLUSIONS: These RWD from the FLEX Registry demonstrate that MPI is predictive of both DRFI prognosis and chemotherapy benefit in HR+HER2- EBC. (NCT03053193).

Adult↗
PubMed2006

Growth-inhibitory effects of human anti-insulin-like growth factor-I receptor antibody (A12) in an orthotopic nude mouse model of anaplastic thyroid carcinoma.

PURPOSE: The insulin-like growth factor-I receptor (IGF-IR) and its ligands have been implicated in the pathogenesis and progression of various cancers, including those arising in the thyroid gland. We therefore evaluated whether the IGF-IR could serve as a potential target for therapy of anaplastic thyroid carcinoma (ATC). EXPERIMENTAL DESIGN: The expression and activation of the IGF-IR and some of its downstream signaling pathway components were evaluated in both human thyroid cancer specimens and thyroid cancer cell lines. The therapeutic potential of a humanized monoclonal antibody (A12) directed against IGF-IR was assessed in vitro and in vivo in an orthotopic model of ATC. Tumor volume and overall survival time were analyzed to evaluate the efficacy of A12 in vivo. RESULTS: IGF-IR was overexpressed in 94% of the thyroid cancers. Blockade of IGF-IR with A12 was effective in attenuating IGF-IR signaling both in vitro and in vivo. However, the inhibitory effects of A12 on cell proliferation were cell line dependent, as those ATC cell lines that had detectable levels of pIGF-IR were more sensitive to A12 treatment. A12 was equally effective in vivo, where it brought approximately 57% (P = 0.041) inhibition in tumor volume. The concomitant use of A12 and irinotecan produced additive effects and resulted in a 93% (P < 0.001) reduction in tumor volume. Blocking IGF-IR blocked Akt phosphorylation and decreased proliferation and microvessel density but increased apoptosis within the tumor xenografts. Our results also highlighted a previously undefined IGF-IR-mediated antiangiogenic effect on tumor-associated endothelium in thyroid cancers. CONCLUSION: Blocking the IGF-IR with A12 seems to be a potential avenue for treating patients with ATC by its direct antitumor effects and its effects on the tumor vasculature.

Animals↗
PubMed2006

Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases reduces growth and metastasis of human salivary adenoid cystic carcinoma in an orthotopic nude mouse model.

We hypothesized that epidermal growth factor (EGF) receptor (EGFR) activation and vascular endothelial growth factor (VEGF)-induced angiogenic signals are important for the progression and metastasis of human salivary adenoid cystic carcinoma (ACC). To test this hypothesis, we evaluated the therapeutic effect of AEE788, a dual inhibitor of EGF and VEGF receptor (VEGFR) tyrosine kinases, on human salivary ACC. In clinical specimens of salivary ACC, EGF and VEGF signaling proteins were expressed at markedly higher levels than in adjacent normal glandular tissues. We examined the effects of AEE788 on salivary ACC cell growth and apoptosis and on the phosphorylation of EGFR and VEGFR-2 in salivary ACC cells. Treatment of salivary ACC cells with AEE788, alone or in combination with chemotherapy, led to growth inhibition, induction of apoptosis, and dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation. To determine the in vivo antitumor effects of AEE788, nude mice with orthotopic parotid tumors were randomized to receive oral AEE788 alone, paclitaxel alone, cisplatin alone, a combination of AEE788 plus paclitaxel, a combination of AEE788 plus cisplatin, or a placebo. AEE788 inhibited tumor growth and prevented lung metastasis in nude mice. To study the mechanism of interaction between AEE788 and chemotherapy, AEE788 was found to potentiate growth inhibition and apoptosis of ACC tumor cells mediated by chemotherapy. Tumors of mice treated with AEE788 and AEE788 plus chemotherapy exhibited down-regulation of activated EGFR and VEGFR-2, increased tumor and endothelial cell apoptosis, and decreased microvessel density, which correlated with a decrease in the level of matrix metalloproteinase-9 and matrix metalloproteinase-2 expression and a decrease in the incidence of vascular metastasis. These data show that EGFR and VEGFR can be molecular targets for therapy of salivary ACC.

Animals↗
PubMed2003

Association between beta2-adrenoceptor polymorphisms and asthma diagnosis among Mexican adults.

BACKGROUND: Recent studies demonstrate that genetic variations in the human beta(2)-adrenergic receptor (beta(2)AR) structure at codons 16 and 27 alter receptor function in vitro and are associated with asthma severity and airway hyperresponsiveness but have not been linked to asthma diagnosis. The nature of the relation in a more homogeneous population is uncertain. OBJECTIVE: We determined frequencies of these polymorphisms to explore the association between beta(2)AR haplotypes and asthma diagnosis and phenotype. METHODS: This is a population-based, case-control study that involves a total sample of 907 unrelated Mexican Mestizos. Genotyping at beta(2)AR was identified by polymerase chain reaction-restriction fragment length polymorphism analysis. Multivariate logistic regression analysis was used to estimate the odds ratio (OR) of the association between beta(2)AR haplotype status and asthma diagnosis. RESULTS: A significant inverse association was found between subjects with Glu27 allele (OR, 0.5; 95% CI, 0.4 to 0.7) and Gly16-Glu27 alleles (OR, 0.5; 95% CI, 0.3 to 0.8) and asthma. Sex differences in this association were explored, given the complex relation between sex and asthma. Among men, a positive association was present between the "Gly16 allele without Glu27" (OR, 2.9; 95% CI, 1.26 to 6.8) and asthma. In contrast, a lower risk of asthma was found among women Gly16-Glu27 alleles (OR, 0.3; 95% CI, 0.2 to 0.6). Nocturnal asthma was associated with the Gly16 allele (OR, 1.8; 95% CI, 1.3 to 2.6). CONCLUSIONS: Variation in the beta(2)AR gene is associated in the pathogenesis of asthma and acts as a disease modifier in nocturnal asthma.

Adult↗
PubMed2003

A meta-analysis of asthma and risk of lung cancer (United States).

OBJECTIVE: To review epidemiologic evidence that asthma is a risk factor for lung cancer, with particular attention to the role of smoking on this association. METHODS: Through MEDLINE computer searches (January 1966 to April 2002) and a review of references, we identified studies with quantitative data on the relation of asthma to lung cancer. Summary estimates of relative risks (RR) were calculated using the fixed-effects model or the random-effects model as appropriate. RESULTS: The combined results from five case-control studies--that presented data limited to individuals who had never smoked--showed a 1.8-fold increase in lung cancer risk among asthmatics (95% confidence interval (CI) = 1.3-2.3). The results from six case-control and four cohort studies, which controlled for smoking history also were significant (RR = 1.7; 95% CI = 1.3-2.2). Finally, to illustrate the potential confounding by tobacco, we combined data from seven cohort studies that did not control for smoking history and found an overall RR of 1.4 (95% CI = 1.2-1.6). CONCLUSIONS: The increased risk of lung cancer among never smoking individuals with asthma supports a direct relation between asthma and lung cancer. There is biological evidence to support this association.

Asthma↗
PubMedDate not supplied

Decision making in abdominoplasty.

BACKGROUND: Improvements and variations in abdominoplasty techniques have complicated patient and procedure selection. The authors describe their guidelines for selecting the ideal procedure to be used with patients by stratifying them into treatment groups according to the presence and location of excess skin and subcutaneous tissue, lipodystrophy, and abdominal wall laxity. METHODS: A prospective study analyzed 151 female patients treated for abdominal contour deformities from January 2004 to July 2005. The patients were systematically classified into five treatment groups: mini-abdominoplasty (5%), standard abdominoplasty (42%), abdominoplasty with liposuction and minimal midline undermining (10%), standard abdominoplasty with removal of deep fat (13%), and circumferential abdominoplasty (30%). RESULTS: The patients had a mean age of 42 years and a mean body mass index (BMI) of 26 kg/m(2). The prevalence of overweight (BMI, 25.0-29.9) was 37%, and that of obesity (BMI > 30.0) was 19%. Comparison of pre- and postoperative photographs included improved tension of the entire abdominal wall, enhancement of the waistline, and increased uniformity of the contour of the abdomen. There was a significant difference in mean BMI between preabdominoplasty (26 kg/m(2)) and postabdominoplasty (24 kg/m(2)) (p = 0.01). The prevalence of overweight and obesity decreased by 8% and 9%, respectively (p = 0.01), and a decrease in BMI occurred within each abdominoplasty subgroup (p = 0.01). The prevalence of complications was 11%. Seroma (4%) and delayed wound healing (4%) were the most common. One case of pulmonary embolus was encountered. Although there was a positive trend in complications with higher BMI, no statistically significant difference was found (p = 0.74). Half of the patients had additional procedures performed without a significant increase in complications (p = 0.5). CONCLUSIONS: The described algorithm for abdominoplasty selection is safe, effective, and flexible, with long-term improvement in abdominal contour and BMI.

Abdomen↗