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المؤلفون: Lisa A. Kottschade, Yiyi Yan
المصدر: JCO Oncology Practice. 16:10s-14s
مصطلحات موضوعية: 0301 basic medicine, Oncology, medicine.medical_specialty, Skin Neoplasms, Drug-Related Side Effects and Adverse Reactions, Referral, medicine.medical_treatment, Disease, Medical Oncology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Internal medicine, medicine, Humans, Endocrine system, Stage (cooking), Adverse effect, Immune Checkpoint Inhibitors, Melanoma, Oncology (nursing), business.industry, Health Policy, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, business, Adjuvant
الوصف: Patients diagnosed with stage III melanoma who have undergone curative-intent surgery still remain at relatively high risk of disease recurrence. Recently approved adjuvant therapies with immune checkpoint inhibitors (ICIs) have brought increased relapse-free and overall survival rates. However, they have introduced a new range of side effects that can be difficult to diagnose, are challenging to treat, and may have lifelong consequences for patients. Oncologists and other members of the oncology care team should be aware of these side effects, including atypical presentations, and be prepared to intervene to prevent increased morbidity and mortality. Oncologists also need to have a low threshold for referral to other subspecialists, as many of these immune-related adverse events (irAEs) need to be comanaged using a multidisciplinary approach. Herein, we present a case that illustrates challenging presentations of endocrinopathy and hepatic irAEs in a patient with stage III melanoma receiving ICI therapy in the adjuvant setting.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::125ec029c7fc35f6b78cd1e635121223
https://doi.org/10.1200/jop.19.00649 -
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المؤلفون: Ashish V. Chintakuntlawar, Lisa A. Kottschade, Alexandra Higgins, Ronald S. Go, Anna Schwecke, Uma Thanarajasingam, Paul J. Hampel, Yiyi Yan, Antoine N. Saliba, Lionel A. Kankeu Fonkoua, Harry E Fuentes-Bayne, Anuhya Kommalapati, Xavier Andrade-Gonzalez, Evandro D. Bezerra, Aref Al-Kali, Alexandra P. Wolanskyj-Spinner, Yanyan Lou, Gita Thanarajasingam, Sagar Rakshit, Candido E. Rivera, Matthew S. Block, Katharine A. Price, Zhuoer Xie, Ariela L. Marshall, Daniel S. Childs
المصدر: American Journal of Hematology. 96
مصطلحات موضوعية: Adult, Male, business.industry, Immune checkpoint inhibitors, MEDLINE, Context (language use), Hematology, Middle Aged, Bioinformatics, Hematologic Diseases, Immune system, Humans, Medicine, Female, Immunotherapy, business, Adverse effect, Immune Checkpoint Inhibitors, Aged
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المؤلفون: Sébastien Faniel, Denis Flandre, Jean-Pierre Raskin, Xiaohui Tang, Yiyi Yan, Valeriya Kilchytska
المصدر: 2021 IEEE Latin America Electron Devices Conference (LAEDC).
مصطلحات موضوعية: Materials science, Passivation, Silicon, business.industry, Gate dielectric, chemistry.chemical_element, Photodetector, Carrier lifetime, Dielectric, Stack (abstract data type), chemistry, Optoelectronics, Spontaneous emission, business
الوصف: This work investigates different Al2O3-based dielectric stacks for various applications, including surface passivation of solar cells and photodetectors, replacement of SiO2 gate dielectric in advanced MOSFETs. Ultra-thin Al2O3/SiO2 (3/2 nm) stacks were deposited on silicon by using different techniques. A reference sample with only a single dry-grown SiO2 layer (3 nm) was prepared for comparison purpose. The effective carrier lifetimes were measured by the contactless photoconductance decay method. The lowest surface recombination velocity was calculated to be 34 cm/s in the Al2O3/SiO2 stack. The negative fixed charge density in the stacks was extracted from C–V characteristics. Our results reveal that the effective carrier lifetimes depend on the stacks deposition techniques and conditions, and provide a guideline for optimization.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::b0fc87362ebb71d3118e0fb0b109ec2a
https://doi.org/10.1109/laedc51812.2021.9437934 -
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المؤلفون: Yiyi Yan, Lisa A. Kottschade, Roxana S. Dronca, Svetomir N. Markovic, Charles L. Loprinzi, Jessica Brandt, Axel Grothey, Robert R. McWilliams, Jesus Vera, Matthew S. Block, Jonas Paludo
المصدر: Supportive Care in Cancer. 27:3869-3875
مصطلحات موضوعية: MAPK/ERK pathway, Trametinib, Kinase, business.industry, Familial Mediterranean fever, Dabrafenib, Pharmacology, medicine.disease, Rash, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Oncology, chemistry, 030220 oncology & carcinogenesis, medicine, Colchicine, 030212 general & internal medicine, medicine.symptom, Adverse effect, business, medicine.drug
الوصف: The most common adverse event (AE) of dabrafenib and trametinib (DT) is pyrexia, which has been reported to occur in up to 71% of patients. Pyrexia resulted in therapy discontinuation in up to 26% of patients that otherwise were benefiting from the treatment. Little is known about the pathogenesis and optimal management of this common AE. We hypothesized that the etiology of pyrexia in patients treated with DT could be extrapolated from DT-related cutaneous adverse effects in which a paradoxical MAPK pathway activation has been identified. Based on preliminary data by our group suggesting an upregulation of the mitogen-activated protein kinases (MAPKs) in human lymphocytes exposed to dabrafenib and trametinib, specifically elevated expression of phosphorylated JNK (p-JNK), p38 MAPK (p-p38 MAPK), and ERK5 (p-ERK5), we hypothesized that the mechanism of MAPK pathway activation with DT therapy is similar to that reported in patients with familial Mediterranean fever (FMF), a rare, inherited condition characterized by episodes of fever and rash that responds exceedingly well to colchicine-based therapy in which the MAPK pathway is hyper-activated. Based on this association, our group explored the use of oral colchicine for the treatment of DT-associated pyrexia in five patients with metastatic melanoma.
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المؤلفون: Jarrett J. Failing, Anagha Bangalore Kumar, Robert R. McWilliams, Svetomir N. Markovic, Roxana S. Dronca, Matthew S. Block, Ying Li, Jonas Paludo, Lisa A. Kottschade, Yiyi Yan, Jesus Vera Aguilera, Henan Zhang, Haidong Dong
المصدر: Melanoma Research
مصطلحات موضوعية: 0301 basic medicine, Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Skin Neoplasms, Disease Response, medicine.medical_treatment, Original Articles: Clinical research, Dermatology, chemotherapy, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Chemoimmunotherapy, Internal medicine, medicine, Humans, Young adult, Lung cancer, Immune Checkpoint Inhibitors, Melanoma, Aged, Chemotherapy, business.industry, Immunotherapy, Middle Aged, medicine.disease, Confidence interval, Blockade, 030104 developmental biology, Treatment Outcome, 030220 oncology & carcinogenesis, chemoimmunotherapy, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, immunotherapy, therapy-responsive T-cells, business
الوصف: Supplemental Digital Content is available in the text.
Management of PD-1 blockade resistance in metastatic melanoma (MM) remains challenging. Immunotherapy or chemotherapy alone provides limited benefit in this setting. Chemo-immunotherapy (CIT) has demonstrated favorable efficacy and safety profiles in lung cancer. Our pre-clinical study showed that in MM patients who have failed PD-1 blockade, the addition of chemotherapy increases CX3CR1+ therapy-responsive CD8+ T-cells with enhanced anti-tumor activity, resulting in improved clinical response. Here, we examined the clinical outcomes of CIT in MM patients after PD-1 blockade failure and the treatment-related changes in CX3CR1+ therapy-responsive CD8+ T-cells. We reviewed MM patients seen between January 2012 and June 2018 who failed anti-PD-1-based therapy and received subsequent CIT, immune checkpoint inhibitors (ICI) or chemotherapy alone. Overall survival (OS), objective response rate (ORR), event-free survival (EFS), and toxicities were assessed. Among 60 patients, 33 received CIT upon disease progression on PD-1 blockade. At a median follow-up of 3.9 years, the CIT group had a median OS of 3.5 years [95% confidence interval (CI) 1.7–NR] vs. 1.8 years (95% CI 0.9–2; P = 0.002) for those who received subsequent ICI (n = 9) or chemotherapy alone (n = 18), with ORR of 59% vs. 15% (P = 0.0003), respectively. The median EFS was 7.6 months (95% CI 6–10) following CIT vs. 3.4 months (95% CI 2.8–4.1; P = 0.0005) following ICI or chemotherapy alone. Therapy-responsive CX3CR1+CD8+ T-cells showed dynamic increase with successful CIT. CIT showed favorable clinical outcomes and acceptable safety profile in PD-1 blockade-resistant patients. CX3CR1+CD8+ therapy-responsive T-cells can be potentially used for monitoring disease response to CIT.URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5a513e0df05dc28790966ff365e4f988
https://pubmed.ncbi.nlm.nih.gov/32404734 -
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المؤلفون: Yiyi Yan
المصدر: JCO oncology practice. 16(2_suppl)
مصطلحات موضوعية: medicine.medical_specialty, Oncology, Oncology (nursing), business.industry, Health Policy, Neoplasms, medicine, Humans, Medical physics, business, Medical Oncology
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68692d246b6468bae7d32ddcd5ba874e
https://pubmed.ncbi.nlm.nih.gov/32045537 -
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المؤلفون: Alexandra B. Gonzalez, Yiyi Yan, Jennifer M. Racz, Tina J. Hieken, James W. Jakub, Lisa A. Kottschade, Svetomir N. Markovic, Matthew S. Block
المصدر: Journal of Surgical Oncology. 117:1164-1169
مصطلحات موضوعية: Male, medicine.medical_specialty, medicine.medical_treatment, Disease, Systemic therapy, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, Progression-free survival, Stage (cooking), Melanoma, Neoadjuvant therapy, Aged, Retrospective Studies, Advanced melanoma, business.industry, Advanced stage, General Medicine, Middle Aged, Prognosis, Response to treatment, Neoadjuvant Therapy, Surgery, Survival Rate, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business, Follow-Up Studies
الوصف: Background Patients with regionally advanced melanoma are at high risk of distant failure and unlikely to be cured by surgery alone. Neoadjuvant therapy may provide benefit in these patients. Objectives To evaluate our experience with neoadjuvant systemic therapy in high-risk stage III patients. Methods Retrospective review of patients with advanced stage III disease who received neoadjuvant therapy between August 2009 and August 2016 at Mayo Clinic Rochester. Results Twenty-three cases met our inclusion criteria, 16 with resectable disease and 7 with unresectable disease. No patients with resectable disease and one patient with borderline resectable disease progressed regionally, prohibiting surgical resection. Five of seven patients with unresectable disease were down-staged to a resectable state. Six of twenty-three (26%) had a CR and five are alive at last follow-up. Fifteen of twenty three patients (65%) progressed with a median progression free survival of 11 months; however, the 5 year overall survival estimate was 84%. Conclusions Neoadjuvant systemic therapy is a reasonable approach for patients with advanced but resectable/borderline resectable disease and the risk of losing regional control is low. Our data also suggest some patients with unresectable disease will be converted to resectable and a complete clinical response to treatment can be obtained in approximately one quater of patients.
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المؤلفون: Ronald S. Go, Ally Higgins, Xavier Andrade-Gonzalez, Gita Thanarajasingam, Uma Thanarajasingam, Paul J. Hampel, Katharine A. Price, Anna Schwecke, Ariela L. Marshall, Harry E Fuentes-Bayne, Antoine N. Saliba, Evandro D. Bezerra, Lionel A. Kankeu Fonkoua, Lisa A. Kottschade, Daniel S. Childs, Aref Al-Kali, Candido E. Rivera, Matthew S. Block, Yanyan Lou, Zhuoer Xie, Sagar Rakshit, Yiyi Yan, Alexandra P. Wolanskyj
المصدر: Blood. 136:31-32
مصطلحات موضوعية: medicine.medical_specialty, Cold agglutinin disease, business.industry, Immunology, Pure red cell aplasia, Cell Biology, Hematology, Neutropenia, medicine.disease, Biochemistry, Pancytopenia, Internal medicine, medicine, Rituximab, Autoimmune hemolytic anemia, Aplastic anemia, Adverse effect, business, medicine.drug
الوصف: Introduction Immune-mediated hematologic disorders are relatively rare but potentially life-threatening immune-related adverse events (irAE) with immune checkpoint inhibitor (ICI) therapy (Shiuan, Beckermann et al 2017). The management strategy often relies on systemic corticosteroids and other immunosuppressant agents in steroid-refractory cases (Brahmer, Lacchetti et al 2018). We hereby describe our institution's experience in diagnosing and managing immune-related hematologic adverse events (ir-h-AE). Methods We retrospectively searched the electronic health record for all ir-h-AE diagnosed by treating providers and confirmed by study authors between 2015 and 2020. The search included patients on ICI and the following conditions: immune-related neutropenia (IRN), autoimmune hemolytic anemia (AIHA), cold agglutinin disease (CAD), immune thrombocytopenia (ITP), immune-related pancytopenia, aplastic anemia (AA), and pure red cell aplasia (PRCA). For AIHA, PRCA, and CAD, partial response (PR) was defined as hemoglobin greater than 10 g/dL but < 12 g/dL and 2 g/dL above the nadir without blood product transfusion. Complete response (CR) was defined as hemoglobin of ≥ 12 g/dL and 2 g/dL above the nadir without blood product transfusion (Peñalver, Alvarez-Larrán et al. 2010). For ITP, CR was defined as platelet count ≥ 100 × 109/L and absence of bleeding. PR was defined as platelet count ≥ 30 × 109/L and ≥ two-fold increase from the baseline count and absence of bleeding (Gómez-Almaguer, Tarín-Arzaga et al. 2013). For IRN, CR was defined as absolute neutrophil count (ANC) ≥ 1500/ mm3 on 2 consecutive measurements separated by 7 days; PR was defined as ANC ≥ 500/ mm3 sustained over 7 days. JMP® 14.1 was used for data analysis. Results Seventeen patients were identified, 9 (52.9%) of whom were female (table 1). Median age was 68 years (range 26-78). The most common pre-existing malignancies were melanoma (6 patients, 35.3%), non-small cell lung cancer (4 patients, 23.5%), and gastrointestinal cancer (3 patients, 17.6%). The ir-h-AE included 7 patients (41.2%) with warm AIHA, 4 (23.5%) with ITP (1 had immune-related pancytopenia that resolved with ITP persisting), 3 (17.6%) with IRN, 1 with AA, 1 with CAD, and 1 with PRCA and mild ITP. All patients had received an ICI dose within 60 days of diagnosis (range 3-52 days, median 18 days). Only 1 patient had a concomitant chronic autoimmune disorder (antinuclear antibody-positive arthritis). Four patients (23.5%) were receiving chemotherapy. Sixteen patients (94.1%) required treatment and received corticosteroids. Eight out of 15 evaluable patients (53.3%) responded to corticosteroids only. Another 4 responders (26.7%) required additional therapies including intravenous immunoglobulins (IVIG) (4, 23.5%) and/or rituximab (4, 23.5%). Overall response rate was 71.4% for AIHA and 100% for IRN. ITP was likely underrepresented in our cohort, and the response rate of 66.7% is likely lower than the response rate in clinical practice. This could be related to the fact that many mild thrombocytopenia cases are not further evaluated in clinical practice. None of our patients died from the sequelae of an ir-h-AE. Two patients (11.8%) died within 30 days of ir-h-AE diagnosis (disseminated intravascular coagulation likely due to the underlying malignancy and sepsis from bacterial pneumonia). At the time of ir-h-AE diagnosis, the malignancy was showing evidence of response in 9 patients (52.9%), progression in 6 patients (35.3%), and stability in 2 patients (11.8%). ICI therapy was permanently discontinued in 9 patients (52.9%) and temporarily held in 6 patients (35.3%). Three of the 5 patients (60%), who were rechallenged with ICI therapy, had recurrence of the same ir-h-AE (AIHA) with adequate response to therapy. Non-hematologic irAE (7 patients, 41.2%) included 3 patients with hepatitis, 2 with thyroiditis, 2 with pneumonitis, 1 with colitis, and 1 with dermatitis. Conclusion Our clinical experience with ir-h-AE highlights the importance of exercising vigilance in assessing the hematologic parameters of patients receiving ICI therapy. While relatively rare, ir-h-AE may impact the clinical course of patients with cancer and their eligibility for therapies that have the potential of offering durable control of the underlying malignancy. ir-h-AE respond to classical therapies including corticosteroids, IVIG, and rituximab. Disclosures Block: Merck: Research Funding; Bristol-Myers Squibb: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Marker Therapeutics: Research Funding; Transgene: Research Funding; Immune Design: Research Funding. Kottschade:Bristol-Myers Squibb: Consultancy, Research Funding.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::de721f7cda81e3a30f90c94e6cc6de50
https://doi.org/10.1182/blood-2020-138657 -
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المؤلفون: Aaron S. Mansfield, Peng Yin, Yiyi Yan, Yinghua Li, Susan M. Harrington, Haidong Dong, Xin Liu
المصدر: Oncotarget
مصطلحات موضوعية: CpG ODN, 0301 basic medicine, CpG Oligodeoxynucleotide, medicine.medical_treatment, T cell, Programmed Cell Death 1 Receptor, Down-Regulation, Antineoplastic Agents, Context (language use), CD8-Positive T-Lymphocytes, tumor immunotherapy, Mice, 03 medical and health sciences, Immune system, Cell Line, Tumor, PD-1, medicine, Animals, business.industry, Neoplasms, Experimental, Immunotherapy, immune checkpoints, Interleukin-12, Immune checkpoint, 3. Good health, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Oligodeoxyribonucleotides, Oncology, IL-12, Immunology, Interleukin 12, business, CD8, Research Paper
الوصف: // Peng Yin 1 , Xin Liu 2 , Aaron S. Mansfield 3 , Susan M. Harrington 1 , Yinghua Li 2 , Yiyi Yan 3 , Haidong Dong 1, 2 1 Department of Urology, Mayo Clinic, Rochester, MN, USA 2 Department of Immunology, Mayo Clinic, Rochester, MN, USA 3 Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA Correspondence to: Haidong Dong, email: Dong.Haidong@mayo.edu Keywords: CpG ODN, IL-12, immune checkpoints, PD-1, tumor immunotherapy Received: February 29, 2016 Accepted: August 24, 2016 Published: September 02, 2016 ABSTRACT CpG oligodeoxynucleotides, as a ligand of toll-like receptor (TLR)-9, have demonstrated promising antitumor effects in some clinical trials; however, its toxicity and low efficacy as a systemic therapy has limited its therapeutic applications. In order to improve its therapeutic efficacy, we investigated the mechanisms of CpG-induced antitumor immunity in the context of CD8 + T cell responses. We show that IL-12 is required for the expansion of IFN-γ producing tumor-reactive CD8 + T cells capable of rejecting tumors. In addition, CpGs reduced PD-1 expression by effector CD8 + T cells via the IL-12 pathway. The combination of CpG and PD-1 blockade show a synergistic effect in generation of systemic antitumor immunity. Our studies define a critical role of IL-12 in CpG-induced antitumor immunity and provide a rationale for combined therapy with TLR agonists and immune checkpoint blockade in cancer treatment.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d103a1136ea60f743eb613ac98aed861
https://doi.org/10.18632/oncotarget.11833 -
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المؤلفون: Yiyi Yan, Thanh P. Ho, Sudhakar K. Venkatesh, Hani S. Alkhatib
المصدر: Journal of Oncology Practice. 15:675-676
مصطلحات موضوعية: Male, Oncology, medicine.medical_specialty, medicine.diagnostic_test, Oncology (nursing), business.industry, Biopsy, Health Policy, medicine.medical_treatment, Hepatic Veno-Occlusive Disease, MEDLINE, Immunotherapy, Middle Aged, Internal medicine, medicine, Humans, business, Melanoma
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eb1981d387989bf8c8d794377dcfdd52
https://doi.org/10.1200/jop.19.00276
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