Letteratura scientifica selezionata sul tema "Next-Generation hormone therapy"
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Articoli di riviste sul tema "Next-Generation hormone therapy"
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Boyce, Eric G., Yvonne Mai e Christopher Pham. "Abaloparatide: Review of a Next-Generation Parathyroid Hormone Agonist". Annals of Pharmacotherapy 52, n. 5 (14 dicembre 2017): 462–72. http://dx.doi.org/10.1177/1060028017748649.
Testo completoAbstract (sommario):
Objective: To review the efficacy, safety, and economics of abaloparatide in the treatment of postmenopausal osteoporosis. Data Sources: PubMed (1966 to October 2017), Clinicaltrials.gov (October 2017), and Scopus (1970 to October 2017) were searched using abaloparatide, Tymlos, BA058, PTHrP 1-34 analog, and parathyroid hormone–related peptide 1-34 analog. Study Selection and Data Extraction: Human studies published in peer-reviewed publications in English were the primary sources for efficacy, safety, and economic data. Data Synthesis: In the 2 randomized, published clinical studies of 24 weeks and 18 months duration, bone mineral density changes were higher for abaloparatide (lumbar spine, 6.7%-11.2%; femoral head, 3.1%-3.2%; total hip, 2.6%-4.2%) compared with placebo (lumbar spine, 0.6%-1.6%; femoral head, −0.4% to 0.8%; total hip, −0.1% to 0.4%; P < 0.05) and compared with teriparatide in the 24-week study (total hip 2.6% vs +0.5%, P < 0.05). New vertebral and nonvertebral fractures occurred in 0.6% and 2.7% of patients on abaloparatide compared with 4.2% and 4.7% on placebo in the 18-month study ( P < 0.05). Abaloparatide appears to have a somewhat higher risk for adverse effects, discontinuation as a result of adverse effects, and serious or severe adverse effects than teriparatide, but teriparatide has a higher risk for hypercalcemia. Pharmacoeconomic modeling appears to favor abaloparatide if differences in efficacy and cost are maintained. Conclusion: Abaloparatide, which has less effect on osteoclasts, is an alternative to teriparatide in patients with postmenopausal osteoporosis who are at high risk for fractures or who have failed antiresorptive therapy based on initial clinical studies and economic modeling.
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Öberg, Kjell, e Steven W. J. Lamberts. "Somatostatin analogues in acromegaly and gastroenteropancreatic neuroendocrine tumours: past, present and future". Endocrine-Related Cancer 23, n. 12 (dicembre 2016): R551—R566. http://dx.doi.org/10.1530/erc-16-0151.
Testo completoAbstract (sommario):
Acromegaly is a hormonal disorder that arises when the pituitary gland secretes excess growth hormone (GH), which in turn stimulates a concomitant increase in serum insulin-like growth factor 1 (IGF-1) levels. Gastroenteropancreatic neuroendocrine tumours (GEP-NET) constitute a heterogeneous group of tumours that can secrete serotonin and a variety of peptide hormones that may cause characteristic symptoms known as carcinoid syndrome or other symptoms and hormonal hypersecretion syndromes depending on the tumour’s site of origin. Current medical therapy for the treatment of acromegaly and GEP-NET involves the administration of somatostatin analogues that effectively suppress excess hormone secretion. After its discovery in 1979, octreotide became the first synthetic biologically stable somatostatin analogue with a short-acting formulation of octreotide introduced into clinical practice in the late 1980s. Lanreotide, another somatostatin analogue, became available in the mid-1990s initially as a prolonged-release formulation administered every 10 or 14 days. Long-acting release formulations of both octreotide (Sandostatin LAR and Novartis) and lanreotide (Somatuline Autogel, Ipsen), based on microparticle and nanoparticle drug-delivery technologies, respectively, were later developed, which allowed for once-monthly administration and improved convenience. First-generation somatostatin analogues remain one of the cornerstones of medical therapy in the management of pituitary and GEP-NET hormone hypersecretion, with octreotide having the longest established efficacy and safety profile of the somatostatin analogue class. More recently, pasireotide (Signifor), a next-generation multireceptor-targeted somatostatin analogue, has emerged as an alternative therapeutic option for the treatment of acromegaly. This review summarizes the development and clinical success of somatostatin analogues.
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Gomes, Jessica Ribeiro, Raphael Brandao Moreira, Matheus Bongers Alessandretti e Marcelo Rocha De Sousa Cruz. "Next-generation sequencing (NGS) for personalized therapy in metastatic breast cancer: Selection of therapy and outcomes." Journal of Clinical Oncology 35, n. 15_suppl (20 maggio 2017): e23166-e23166. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e23166.
Testo completoAbstract (sommario):
e23166 Background: Treatment for metastatic breast cancer (MBC) has been driven by hormone receptors, HER2 expressions or their absence. Resistance to therapy and progressive disease will occur and empirical chemotherapy lines usually are the next steps. We aim to analyze the role of next-generation sequencing (NGS) for a personalized therapy in metastatic breast cancer and its potential clinical benefit. Methods: We included patients diagnosed with MBC treated at Centro Oncologico Antonio Ermirio de Moraes – Brazil from April 2013 to December 2016. All patients had metastasis accessible for biopsy. The tumor tissue was stored in paraffin and then analyzed by NGS-based assay that identifies genomic alterations within 236 genes. Results: 19 patients with MBC were evaluated (10 triple-negative; 4 HER2-positive; 5 hormonal receptor positive/HER2-negative). The most frequent and relevant genomic alterations identified by NGS assay were in the following genes: 13 TP53 (68.4%); 4 ERBB2 (21%); 4 PTEN (21%); 4 FGFR (21%); 3 PIK3CA (15.8%); 2 BRCA (10.5%); 2 ATM (10.5%); 2 AKT (10.5%); 2 MYC (10.5%); 1 CCND1 (5.3%); and 1 KRAS (5.3%). The NGS assay was able to suggest further therapy in 16/19 patients (84%). The suggested therapies would not be an empirical option according to the cancer’s subtype in 12/16 patients (75%). Therapy could be personalized in nine patients, across multiple lines of therapies (median of 5th line, with a range of 1-14). Median PFS was 6 months, and 8/9 patients (90%) achieved an objective response with the treatment indicated by NGS. Therefore, the assay provided clinical benefit in 42% of patients. Conclusions: NGS panel identified potentially actionable alterations in the majority of patients with MBC (84%). The overall clinical benefit with use of NGS-based assay was 42%. Further studies are necessary to better evaluate the role of NGS for a personalized therapy in MBC.
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Payne, Forrest W., Bradley Ledden e Greg Lamps. "Capabilities of Next-Generation Patch Pump: Improved Precision, Instant Occlusion Detection, and Dual-Hormone Therapy". Journal of Diabetes Science and Technology 13, n. 1 (24 maggio 2018): 49–54. http://dx.doi.org/10.1177/1932296818776028.
Testo completoAbstract (sommario):
Insulin pumps allow patients to attain better blood glucose control with more lifestyle flexibility. Their size and cost, however, limit their usefulness. Current CSII pumps are bulky, intrusive, and expensive. SFC Fluidics is addressing these problems by developing a new type of wearable patch pump based on the patented electro-chemiosmotic (ECO) microfluidic pumping technology. This nonmechanical pumping technology allows accurate and precise delivery of very small amounts of insulin and/or other drugs, including concentrated insulin. The pump engine is small and can be made inexpensively from injection molded parts, allowing its use in a disposable or semidisposable pod format. In addition, a single ECO pump engine can be used to deliver two drugs through independent pathways. Other features of SFC Fluidics’ pod include latching safety valves that prevent accidental overdosing of insulin due to pressure changes and an instantaneous occlusion sensor that can immediately detect delivery failure at the first missed dose. These features allow for the development of a series of patch pumps that will offer users the benefit of CSII therapy in a more discreet and reliable patch pump form.
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Frolova, M. A., E. B. Glazkova e M. B. Stenina. "Palbociclib in the first line combination hormone therapy of HER2- negative metastatic hormone-dependent breast cancer. Clinical follow-up". Medical Council, n. 10 (19 luglio 2018): 158–60. http://dx.doi.org/10.21518/2079-701x-2018-10-158-160.
Testo completoAbstract (sommario):
According with the present-day ideas, sequential lines of hormone therapy including those in patients with visceral metastases and multiple lesions form the basis of the treatment of HER2-negative metastatic hormone-dependent breast cancer. These measures make it possible to exercise the long-term control of the disease and maintain a good quality of life. In recent years, the clinical practice comprises the next-generation drugs that potentiate the effect of hormone therapy. These include cyclindependent kinases 4/6 inhibitors. Palbociclib (Ibransa, Pfizer) is the first representative of this class approved in Russia for the treatment of disseminated hormone-dependent breast cancer. The PALOMA-2 study demonstrated the high efficacy of the palbociclib combined with letrozole as a first-line hormone therapy. In the palbociclib and letrozole combination arm, the median time to progression was 27,6 months compared to 14,5 months in the letrozole monotherapy arm (p <0,001). The presented clinical case demonstrates the possibility of long-term successful control of the disease using palbociclib combined with letrozole hormone therapy.
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Mayer, E. "Abstract ED08-02: Next generation therapeutics in hormone positive breast cancer: balancing efficacy and tolerability". Cancer Research 84, n. 9_Supplement (2 maggio 2024): ED08–02—ED08–02. http://dx.doi.org/10.1158/1538-7445.sabcs23-ed08-02.
Testo completoAbstract (sommario):
Abstract The past several years have brought a wealth of new and emerging novel agents for the management of both early and advanced hormone repcetor positive breast cancer, including inhibitors of PIK3CA, mTOR, AKT, CDK4/6, PARP, as well as oral SERDs. These agents have significantly improved survival outcomes for many patients, but progress may come at the cost of specific and sometimes challeging side effects, whcih may threaten the ability to keep a patient on a therapy that is providing benefit. We will review a spectrum of agents, the expected side effect profiles, and strategies to mitigate toxicity and maximize therapeutic index. Citation Format: E. Mayer. Next generation therapeutics in hormone positive breast cancer: balancing efficacy and tolerability [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED08-02.
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Gaspard, Ulysse, Melanie Taziaux, Maud Jost, Sven O. Skouby, Rogerio A. Lobo e Jean-Michel Foidart. "Estetrol (E4), the next generation hormone therapy (HT) for menopausal symptoms: phase 2b clinical trial results". Maturitas 124 (giugno 2019): 153. http://dx.doi.org/10.1016/j.maturitas.2019.04.122.
Testo completo
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Lv, Dan, Binliang Liu, Bo Lan, Lixi Li, Xiaoying Sun e Fei Ma. "Clinical value of next-generation sequencing in endocrine therapy for advanced hormone receptor–positive/HER2-negative breast cancer." Journal of Clinical Oncology 40, n. 16_suppl (1 giugno 2022): 1062. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.1062.
Testo completoAbstract (sommario):
1062 Background: Acquired gene mutation is a major mechanism of resistance to endocrine therapy in hormone receptor (HR)-positive advanced breast cancer. Circulating tumor DNA (ctDNA) facilitates the current assessment of the genomic profile in patients with advanced cancer. We performed this clinical trial to determine the landscape of gene mutation before endocrine therapy, to search for molecular markers of endocrine therapy efficacy, and to explore the clinical value of ctDNA to guide precise endocrine therapy in patients with advanced breast cancer. Methods: We conducted an open-label, single-center, multicohort, prospective study. Patients were women with pathologically and immunohistochemically confirmed HR-positive/HER-2-negative patients with advanced breast cancer. Patients relapsed during or after adjuvant endocrine therapy or progressed after completing at least one previous line of treatment for advanced breast cancer. Patients were assigned to four parallel treatment cohortsmatched to mutations identified in ctDNA: 1) cohort A comprised patients with abnormal activation of PI3K/Akt/mTOR pathway signal, preferred mTOR inhibitor combined with endocrine therapy; 2) cohort B comprised patients with ESR1 mutation and who did not use fulvestrant before, preferred fulvestrant; 3) cohort C comprised patients with HER2 mutations, preferred pyrotinib combined with endocrine therapy; 4) cohort D comprised patients with no significant gene mutation, making treatment plan according to the actual clinical situation. If more than one mutation was identified, the priority of entry is cohorts C, cohorts A and cohort B. In the A-D cohort, patients who obey the treatment plan are the compliance group, and patients who do not obey the treatment plan are the violation group. The primary endpoints were progression-free survival (PFS), and the secondary endpoints included overall survival time (OS). Results: A total of 113 patients underwent NGS detection of ctDNA, and 84 patients were enrolled in the study. In all cohorts, combined median PFS was 4.9 months, and the median PFS in the compliance group was 3.0 months longer than in the violation group (6.03 vs 3.03 months, p = 0.0222, HR = 0.5743, 95%CI 0.3273-1.007). In cohort C, the median PFS was 11.1 months in the compliance group and 2.22 months in the violation group (p = 0.0067, HR = 0.1980, 95%CI 0.032-1.22). There was no significant difference in the median PFS between patients with and without compliance with the treatment protocol in cohort A and cohort B (p = 0.5054 and 0.7325, respectively). Conclusions: The study suggested that ctDNA detection may guide the optimal endocrine therapy strategy for patients with advanced breast cancer and achieve the benefit of progression free survival. NGS detection might distinguish patients with HER2 mutation and provide new treatment strategies. Clinical trial information: NCT03786575.
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Hempel, Dirk, Florian Ebner, Valeria Milani, Wolfgang Janni, Amelie De Gregorio, Andreas Gaumann, Zeljka Trepotec, Arun Garg e Louisa Hempel. "Real-world data analysis of next generation sequencing and protein expression in metastatic breast cancer patients." Journal of Clinical Oncology 38, n. 15_suppl (20 maggio 2020): e13005-e13005. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e13005.
Testo completoAbstract (sommario):
e13005 Background: Next generation sequencing (NGS) together with protein expression analysis is back bone of molecularly targeted therapy in precision medicine. The present study shows the retrospective analysis of our experience with NGS using a panel of 324 genes in combination with protein expression in patients with metastatic breast cancer (mBC) over the last 18 months. The primary objective of this study was to analyze the prevalence of individual genetic alterations combined with protein expression to define potential targets for an individualized therapy. Methods: We analyzed 41 patients with advanced BC using solid tumor genomic profiling test. The test was used to detect clinically relevant genomic alterations (point mutations, indels, rearrangements, CNAs, tumor mutation burden (TMB) and microsatellite instability (MSI)) and to support the selection of appropriate targeted therapy. The protein expression (hormon receptors, ERBB2 and PDL1) of tumors was analyzed by immunohistochemistry (IHC). Results: The most common BC subtypes were HR+/ERBB2- (n = 20), followed by triple-negative (n = 15), and HER2+ BC (n = 9). 41 different genetic alterations were reported. Most patients had more than one genetic alteration (n = 27), as determined by NGS. The most common alterations were PIK3CA (n = 14), out of which 11 (78%) were hormone-receptor positive/ERBB2 negative. Conclusions: The NGS of mBC supports the decision for the most promising treatment option in 58,5% of our patients with a Tier I evidence. For an appropriate treatment decision it is necessary to evaluate gene alterations und protein expression of metastases in account. For an appropriate interpretation of rare gene alterations in mBC basket trials on basis of real world data are necessary. We founded the OnkoVision alliance to bring MTB into clinically routine and to identify appropriate patients for basket trials.
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Ligibel, Jennifer A., e Eric P. Winer. "The Aromatase Inhibitors as Adjuvant Therapy for Hormone Receptor-Positive Breast Cancer". Journal of the National Comprehensive Cancer Network 1, n. 2 (aprile 2003): 215–21. http://dx.doi.org/10.6004/jnccn.2003.0020.
Testo completoAbstract (sommario):
Adjuvant hormonal therapy has been shown to decrease the risk of breast cancer recurrence and overall mortality in patients with hormone receptor-positive breast cancer. Tamoxifen has been used in this setting for many years, both in premenopausal and postmenopausal patients. Tamoxifen is not devoid of toxicity, and attempts have been made to develop newer hormonal agents with better efficacy and less toxicity. The aromatase inhibitors have shown equivalent or superior efficacy to tamoxifen in the treatment of metastatic breast cancer, and efforts are underway to determine the role of these agents in early breast cancer. The ATAC trial recently showed that use of the third-generation aromatase inhibitor anastrozole in the adjuvant setting led to a modest improvement in relapse-free survival as compared with tamoxifen. Patients treated with anastrozole were also less likely to develop uterine cancer or experience a thromboembolic event. However, patients treated with anastrozole were more likely than those treated with tamoxifen to suffer a fracture or other musculosketal problem. An ASCO technology assessment panel reviewed the relevant data and issued a consensus statement regarding the use of aromatase inhibitors in the adjuvant setting. In general, the panel favored the continued use of tamoxifen as adjuvant hormonal therapy for most postmenopausal women. Within the next few years, further data from the ATAC trial and from other trials of aromatase inhibitors in the adjuvant setting should be available to guide treatment recommendations for this patient population.
Tesi sul tema "Next-Generation hormone therapy"
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Boue, Antoine. "Ιmpact cοgnitif des hοrmοnοthérapies du cancer de la prοstate : changements cοgnitifs οbjectifs et subjectifs cοnsécutifs à la déprivatiοn andrοgénique seule οu assοciée à une hοrmοnοthérapie de nοuvelle génératiοn". Electronic Thesis or Diss., Normandie, 2024. http://www.theses.fr/2024NORMC414.
Testo completoAbstract (sommario):
La déprivation androgénique est un traitement de référence du cancer de la prostate avancé. De nouveaux agents bloquant de façon puissante l’axe du récepteur des androgènes ont été conçus pour les patients présentant une résistance à la castration. Parmi eux, l’enzalutamide et l’acétate d’abiratérone ont été approuvés pour le traitement du cancer de la prostate métastatique en combinaison avec une déprivation androgénique. La déprivation androgénique seule est susceptible d’impacter la cognition. Les personnes âgées constituent la majorité des patients traités pour un cancer de la prostate et sont plus à risque de présenter des troubles cognitifs. Chez ces patients, les troubles de la cognition sont susceptibles de se répercuter sur l’autonomie et le déroulement des soins. Cette thèse avait pour objectif d’évaluer l’impact cognitif des hormonothérapies du cancer de la prostate. Une méta-analyse a été menée pour identifier les aspects de la cognition les plus affectés par ces hormonothérapies. Elle a montré un déclin de la cognition subjective (auto-perception de la cognition mesurée par questionnaire) au cours d’une déprivation androgénique seule ou associée à une hormonothérapie de nouvelle génération. De plus, une étude a été conduite auprès de patients âgés de 70 ans et plus traités par enzalutamide ou acétate d’abiratérone pour un cancer de la prostate métastatique résistant à la castration. Avant l’initiation du traitement, ces patients âgés présentaient des troubles cognitifs fréquents. L’ajout de l’enzalutamide ou de l’acétate d’abiratérone à la déprivation androgénique a impacté la cognition objective (vitesse de traitement et attention, mesurées avec des tests) et la cognition subjectiveAndrogen deprivation is a standard-of-care option for advanced prostate cancer. New androgen receptor pathway inhibitors have been developed for patients with castration resistance. Among them, enzalutamide and abiraterone acetate are used for the treatment of metastatic prostate cancer in combination with androgen deprivation therapy. Androgen deprivation alone is known to impact cognition. Elderly patients, who represent the majority of prostate cancer patients, are at higher risk of cognitive impairment. In these patients, cognitive impairment can affect their autonomy and the course of care.This thesis aimed to evaluate the cognitive impact of hormone therapy for prostate cancer. A meta-analysis was conducted to identify the cognitive domains most affected by these treatments. It revealed a decline in subjective cognition (self-perceived cognition assessed with questionnaire) during androgen deprivation therapy alone or in combination with next-generation hormone therapy. In addition, a study was conducted with patients aged 70 and older, treated with enzalutamide or abiraterone acetate for metastatic castration-resistant prostate cancer. Before treatment, these patients exhibited frequent cognitive impairment. The addition of enzalutamide or abiraterone acetate to androgen deprivation therapy impacted both objective (processing speed and attention, assessed with cognitive tests) and subjective cognition
Libri sul tema "Next-Generation hormone therapy"
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Bornstein, Kate. Gender outlaws: The next generation. Berkeley, CA: Seal Press, 2010.
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Bornstein, Kate, e S. Bear Bergman. Gender Outlaws: The Next Generation. Basic Books, 2010.
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Gender Outlaws: The Next Generation. Seal Press, 2010.
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Gender outlaws: The next generation. Berkeley, CA: Seal Press, 2010.
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Gender outlaws: The next generation. Berkeley, USA: Seal Press, 2010.
Cerca il testo completoCapitoli di libri sul tema "Next-Generation hormone therapy"
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Miyata, Yasuyoshi, Yohei Shida, Tomohiro Matsuo, Tomoaki Hakariya e Hideki Sakai. "Reconsideration of Hormonal Therapy in the Era of Next‐ Generation Hormonal Therapy". In Prostate Cancer - Leading-edge Diagnostic Procedures and Treatments. InTech, 2016. http://dx.doi.org/10.5772/63282.
Testo completoAtti di convegni sul tema "Next-Generation hormone therapy"
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Bittencourt, Yuri Cardoso Rodrigues Beckedorff, Lucas Soares Almada, Tatiana Strava Corrêa, Daniele Xavier Assad, Marina Sahade Gonçalves, Andrea Kazumi Shimada, Artur Katz e Romualdo Barroso-Sousa. "SOMATIC MUTATIONAL LANDSCAPE CHARACTERIZATION OF METASTATIC BREAST CANCER IN BRAZIL". In Brazilian Breast Cancer Symposium 2022. Mastology, 2022. http://dx.doi.org/10.29289/259453942022v32s2025.
Testo completoAbstract (sommario):
Objective: Breast cancer (BC) is the most common malignancy among Brazilian women after non-melanoma skin cancer. The mutational landscape of BC in Brazil is unknown. This study describes the mutational profile of a cohort of patients with metastatic breast cancer (MBC) who had undergone next-generation sequencing (NGS) using a comprehensive somatic tumor panel. Methods: We retrospectively reviewed medical records from MBC patients. The mutational profile, clinical, and demographic characteristics were abstracted. Furthermore, the patterns of ordering the panel and its usefulness for a clinical decision were evaluated. Results: We found 54 female patients who fulfilled the above criteria. The median age was 58 years (32–86). Most tumors tested were hormone receptor-positive (74%), followed by triple-negative (20.3%), hormone receptor-positive/HER2-positive (3.7%), and HER-2 positive (1.85%). The median time between the diagnosis of metastatic disease and the NGS execution was 40 months (0–112), and only three patients (5.5%) had not received systemic treatment prior to the test recommendation. Somatic mutations were identified in 94.4% (n=51) of the patients, mainly in PIK3CA (48.1%), TP53 (42.5%), and ESR1 (18.5%) genes. Tumor burden mutation (TMB) was informed in 61.1% (n=33) somatic panels, and 15.1% (n=5) had tumors with TMB ≥10 mutations/megabase. Approved genome-driven cancer therapy was found in 54.9% (n=28), and eight patients (28.5%) received it. Conclusion: This study showed a high proportion of actionable somatic genomic alterations, and it reinforces the growing usefulness of a comprehensive NGS tumor somatic panel in managing patients with MBC.
Rapporti di organizzazioni sul tema "Next-Generation hormone therapy"
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Tucker, Mark L., Shimon Meir, Amnon Lers, Sonia Philosoph-Hadas e Cai-Zhong Jiang. Elucidation of signaling pathways that regulate ethylene-induced leaf and flower abscission of agriculturally important plants. United States Department of Agriculture, gennaio 2012. http://dx.doi.org/10.32747/2012.7597929.bard.
Testo completoAbstract (sommario):
The Problem: Abscission is a highly regulated process, occurring as a natural terminal stage of development, in which various organs are separated from the parent plant. In most plant species, the process is initiated by a decrease in active auxin in the abscission zone (AZ) and an increase in ethylene, and may be accelerated by postharvest or environmental stresses. Another potential key regulator in abscission is IDA (Inflorescence Deficient in Abscission), which was identified as an essential peptide signal for floral organ abscission in Arabidopsis. However, information is still lacking regarding the molecular mechanisms integrating all these regulators. In our previous BARD funded research we made substantial progress towards understanding these molecular events in tomato, and the study is still in progress. We established a powerful platform for analysis of genes for regulatory proteins expressed in AZ. We identified changes in gene expression for several transcription factors (TFs) directly linked to ethylene and auxin signaling and several additional regulatory proteins not so obviously linked to these hormones. Moreover, we demonstrated using a virus-induced gene silencing (VIGS) assay that several play a functional role in the onset of abscission. Based on these results we have selected 14 genes for further analysis in stably transformed tomato plants. All 14 genes were suppressed by RNA interference (RNAi) using a constitutive promoter, and 5 of them were also suppressed using an abscission-specific promoter. Transformations are currently at different stages of progress including some lines that already display an abscission phenotype. Objectives: We propose here to (1) complete the functional analysis of the stably transformed tomato plants with T2 lines and perform transcriptome analysis using custom abscission-specific microarrays; (2) conduct an indepth analysis of the role of IDA signaling in tomato leaf and flower abscission; (3) perform transcriptome and proteome analyses to extend the earlier gene expression studies to identify transcripts and proteins that are highly specific to the separation layer (i.e., target cells for cell separation) prior to the onset of abscission; (4) extend and compliment the work in tomato using a winnowed set of genes in soybean. Methodology: Next Generation Sequencing (NGS) of mRNA will be used to further increase the list of abscission-associated genes, and for preparation of a custom tomato abscission microarray to test altered gene expression in transgenic plants. Tandem mass spectrometry (LC-MS/MS) of protein extracts from leaf petiole, flower pedicel and their AZ tissues will be used to identify the proteome of the AZ before and during abscission. AZ-specific gene promoters will be used in stably transformed tomato plants to reduce non-target phenotypes. The bean pod mottle virus (BPMV) plasmid vectors will be used for VIGS analysis in soybean. Expected Contribution: Our study will provide new insights into the regulation of ethylene-induced abscission by further revealing the role of key regulators in the process. This will permit development of novel techniques for manipulating leaf and flower abscission, thereby improving the postharvest performance of agriculturally important crops.