-
71دورية أكاديمية
المؤلفون: Toussi, Atrin, Mans, Nicole, Welborn, Jeanna, Kiuru, Maija
المصدر: Journal of Cutaneous Pathology. 47(7)
مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Cancer, Rare Diseases, Genetic Testing, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Adult, Aged, Aged, 80 and over, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase Inhibitor p16, Genes, p16, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Melanoma, Microphthalmia-Associated Transcription Factor, Middle Aged, Nevus, Pigmented, Phenotype, Receptor, Melanocortin, Type 1, Shelterin Complex, Telomerase, Telomere-Binding Proteins, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, Young Adult, CDKN2A, germline mutation, hereditary, melanocytic nevus, melanoma, Clinical Sciences, Dermatology & Venereal Diseases, Clinical sciences
الوصف: Nearly 15% of melanomas occur in patients with a family history and a subset of these patients have a germline mutation in a melanoma predisposing gene. CDKN2A mutations are responsible for the majority of hereditary melanoma, but many other susceptibility genes have been discovered in recent years, including CDK4, TERT, ACD, TERF2IP, POT1, MITF, MC1R, and BAP1. Additionally, melanoma risk is increased in mixed cancer syndromes caused by mutations in PTEN, BRCA2, BRCA1, RB1, and TP53. While early onset, multiple tumors, and family cancer history remain the most valuable clinical clues for hereditary melanoma, characteristic epithelioid cytology of melanocytic tumors may suggest an underlying BAP1 mutation. Herein, we review the clinical and histopathologic characteristics of melanocytic tumors associated with these germline mutations and discuss the role of genetic counseling.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/1jz7b7f1Test
-
72دورية أكاديميةPhase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma
المؤلفون: Algazi, Alain P, Twitty, Christopher G, Tsai, Katy K, Le, Mai, Pierce, Robert, Browning, Erica, Hermiz, Reneta, Canton, David A, Bannavong, Donna, Oglesby, Arielle, Francisco, Murray, Fong, Lawrence, Pittet, Mikael J, Arlauckas, Sean P, Garris, Christopher, Levine, Lauren P, Bifulco, Carlos, Ballesteros-Merino, Carmen, Bhatia, Shailender, Gargosky, Sharron, Andtbacka, Robert HI, Fox, Bernard A, Rosenblum, Michael D, Daud, Adil I
المصدر: Clinical Cancer Research. 26(12)
مصطلحات موضوعية: Clinical Research, Cancer, Clinical Trials and Supportive Activities, Adult, Aged, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Case-Control Studies, Female, Follow-Up Studies, Humans, Interleukin-12, Male, Melanoma, Middle Aged, Prognosis, Programmed Cell Death 1 Receptor, Prospective Studies, Oncology and Carcinogenesis, Oncology & Carcinogenesis
الوصف: PurposeTumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a low likelihood of response to PD-1 blockade. We conducted a prospective multicenter phase II trial of intratumoral plasmid IL-12 (tavokinogene telseplasmid; "tavo") electroporation combined with pembrolizumab in patients with advanced melanoma with low frequencies of checkpoint positive cytotoxic lymphocytes (cpCTL).Patients and methodsTavo was administered intratumorally days 1, 5, and 8 every 6 weeks while pembrolizumab (200 mg, i.v.) was administered every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST, secondary endpoints included duration of response, overall survival and progression-free survival. Toxicity was evaluated by the CTCAE v4. Extensive correlative analysis was done.ResultsThe combination of tavo and pembrolizumab was well tolerated with adverse events similar to those previously reported with pembrolizumab alone. Patients had a 41% ORR (n = 22, RECIST 1.1) with 36% complete responses. Correlative analysis showed that the combination enhanced immune infiltration and sustained the IL-12/IFNγ feed-forward cycle, driving intratumoral cross-presenting dendritic cell subsets with increased TILs, emerging T cell receptor clones and, ultimately, systemic cellular immune responses.ConclusionsThe combination of tavo and pembrolizumab was associated with a higher than expected response rate in this poorly immunogenic population. No new or unexpected toxicities were observed. Correlative analysis showed T cell infiltration with enhanced immunity paralleling the clinical activity in low cpCTL tumors.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/59t2b8v3Test
-
73دورية أكاديمية
المؤلفون: Patel, Sandip P, Othus, Megan, Chae, Young Kwang, Giles, Francis J, Hansel, Donna E, Singh, Preet Paul, Fontaine, Annette, Shah, Manisha H, Kasi, Anup, Al Baghdadi, Tareq, Matrana, Marc, Gatalica, Zoran, Korn, W Michael, Hayward, Jourdain, McLeod, Christine, Chen, Helen X, Sharon, Elad, Mayerson, Edward, Ryan, Christopher W, Plets, Melissa, Blanke, Charles D, Kurzrock, Razelle
المصدر: Clinical Cancer Research. 26(10)
مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Immunology, Rare Diseases, Cancer, Clinical Research, Orphan Drug, Health Disparities, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, CTLA-4 Antigen, Female, Follow-Up Studies, Humans, Ipilimumab, Male, Middle Aged, Neuroendocrine Tumors, Nivolumab, Prognosis, Programmed Cell Death 1 Receptor, Prospective Studies, Survival Rate, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
الوصف: PurposeImmune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).Patients and methodsWe performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity.ResultsThirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.ConclusionsIpilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease.
وصف الملف: application/pdf
-
74دورية أكاديمية
المؤلفون: Strosberg, Jonathan, Mizuno, Nobumasa, Doi, Toshihiko, Grande, Enrique, Delord, Jean-Pierre, Shapira-Frommer, Ronnie, Bergsland, Emily, Shah, Manisha, Fakih, Marwan, Takahashi, Shunji, Piha-Paul, Sarina A, O'Neil, Bert, Thomas, Sajeve, Lolkema, Martijn P, Chen, Menghui, Ibrahim, Nageatte, Norwood, Kevin, Hadoux, Julien
المصدر: Clinical Cancer Research. 26(9)
مصطلحات موضوعية: Digestive Diseases, Clinical Research, Cancer, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, B7-H1 Antigen, Disease Progression, Drug Resistance, Neoplasm, Female, Humans, Male, Middle Aged, Neuroendocrine Tumors, Programmed Cell Death 1 Receptor, Survival Rate, Oncology and Carcinogenesis, Oncology & Carcinogenesis
الوصف: PurposeKEYNOTE-158 (ClinicalTrials.gov identifier: NCT02628067) investigated the efficacy and safety of pembrolizumab across multiple cancers. We present results from patients with previously treated advanced well-differentiated neuroendocrine tumors (NET).Patients and methodsPembrolizumab 200 mg was administered every 3 weeks for 2 years or until progression, intolerable toxicity, or physician/patient decision. Tumor imaging was performed every 9 weeks for the first year and then every 12 weeks. Endpoints included objective response rate (ORR) per RECIST v1.1 by independent central radiologic review (primary) and duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (secondary).ResultsA total of 107 patients with NETs of the lung, appendix, small intestine, colon, rectum, or pancreas were treated. Median age was 59.0 years (range, 29-80), 44.9% had ECOG performance status 1, 40.2% had received ≥3 prior therapies for advanced disease, and 15.9% had PD-L1-positive tumors (combined positive score ≥1). Median follow-up was 24.2 months (range, 0.6-33.4). ORR was 3.7% (95% CI, 1.0-9.3), with zero complete responses and four partial responses (three pancreatic and one rectal) all in patients with PD-L1-negative tumors. Median DOR was not reached, with one of four responses ongoing after ≥21 months follow-up. Median PFS was 4.1 months (95% CI, 3.5-5.4); the 6-month PFS rate was 39.3%. Median OS was 24.2 months (95% CI, 15.8-32.5). Treatment-related adverse events (AE) occurred in 75.7% of patients, 21.5% of whom had grade 3-5 AEs.ConclusionsPembrolizumab monotherapy showed limited antitumor activity and manageable safety in patients with previously treated advanced well-differentiated NETs.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/26j6b562Test
-
75دورية أكاديمية
المؤلفون: Tolcher, Anthony W, Kurzrock, Razelle, Valero, Vincente, Gonzalez, Rene, Heist, Rebecca S, Tan, Antoinette R, Means-Powell, Julie, Werner, Theresa L, Becerra, Carlos, Wang, Chenxi, Leonowens, Cathrine, Kalyana-Sundaram, Shanker, Kleha, Joseph F, Gauvin, Jennifer, D’Amelio, Anthony M, Ellis, Catherine, Ibrahim, Nageatte, Yan, Li
المصدر: Cancer Chemotherapy and Pharmacology. 85(4)
مصطلحات موضوعية: Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Trials and Supportive Activities, Clinical Research, Cancer, Evaluation of treatments and therapeutic interventions, 6.2 Cellular and gene therapies, 6.1 Pharmaceuticals, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Cohort Studies, Diamines, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, MAP Kinase Kinase 1, MAP Kinase Kinase 2, Male, Maximum Tolerated Dose, Melanoma, Middle Aged, Prognosis, Proto-Oncogene Proteins c-akt, Pyrazoles, Pyridones, Pyrimidinones, Tissue Distribution, Triple Negative Breast Neoplasms, Young Adult, AKT inhibitor, BRAF-wild type melanoma, MEK inhibitor, Trametinib, Triple-negative breast cancer, Uprosertib, Oncology & Carcinogenesis, Oncology and carcinogenesis, Pharmacology and pharmaceutical sciences
الوصف: PurposeThis study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition.MethodsThis was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD.ResultsAdverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/6c2779pgTest
-
76دورية أكاديمية
المؤلفون: Srivastava, Ruchi, Coulon, Pierre-Gregoire A, Prakash, Swayam, Dhanushkodi, Nisha R, Roy, Soumyabrata, Nguyen, Angela M, Alomari, Nuha I, Mai, Uyen T, Amezquita, Cassendra, Ye, Caitlin, Maillère, Bernard, BenMohamed, Lbachir
المصدر: Journal of Virology. 94(7)
مصطلحات موضوعية: HIV/AIDS, Sexually Transmitted Infections, Infectious Diseases, Vaccine Related, Immunization, Prevention, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Adult, Aged, Animals, Antigens, Viral, Asymptomatic Infections, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Computer Simulation, Epitopes, T-Lymphocyte, Female, HLA-DR Antigens, Haplotypes, Humans, Immunodominant Epitopes, Immunologic Memory, Interferon-gamma, Keratitis, Herpetic, Lysosomal-Associated Membrane Protein 1, Male, Mice, Mice, Transgenic, Middle Aged, Phenotype, Viral Proteins, Young Adult, CD4(+) T cells, HLA transgenic mice, HSV-1, UL46, VP11/12, epitope, human, mapping, tegument protein, CD4+ T cells, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology
الوصف: While the role of CD8+ T cells in the control of herpes simplex virus 1 (HSV-1) infection and disease is gaining wider acceptance, a direct involvement of effector CD4+ T cells in this protection and the phenotype and function of HSV-specific human CD4+ T cell epitopes remain to be fully elucidated. In the present study, we report that several epitopes from the HSV-1 virion tegument protein (VP11/12) encoded by UL46 are targeted by CD4+ T cells from HSV-seropositive asymptomatic individuals (who, despite being infected, never develop any recurrent herpetic disease). Among these, we identified two immunodominant effector memory CD4+ TEM cell epitopes, amino acids (aa) 129 to 143 of VP11/12 (VP11/12129-143) and VP11/12483-497, using in silico, in vitro, and in vivo approaches based on the following: (i) a combination of the TEPITOPE algorithm and PepScan library scanning of the entire 718 aa of HSV-1 VP11/12 sequence; (ii) an in silico peptide-protein docking analysis and in vitro binding assay that identify epitopes with high affinity to soluble HLA-DRB1 molecules; and (iii) an ELISpot assay and intracellular detection of gamma interferon (IFN-γ), CD107a/b degranulation, and CD4+ T cell carboxyfluorescein succinimidyl ester (CFSE) proliferation assays. We demonstrated that native VP11/12129-143 and VP11/12483-497 epitopes presented by HSV-1-infected HLA-DR-positive target cells were recognized mainly by effector memory CD4+ TEM cells while being less targeted by FOXP3+ CD4+ CD25+ regulatory T cells. Furthermore, immunization of HLA-DR transgenic mice with a mixture of the two immunodominant human VP11/12 CD4+ TEM cell epitopes, but not with cryptic epitopes, induced HSV-specific polyfunctional IFN-γ-producing CD107ab+ CD4+ T cells associated with protective immunity against ocular herpes infection and disease.IMPORTANCE We report that naturally protected HSV-1-seropositive asymptomatic individuals develop a higher frequency of antiviral effector memory CD4+ TEM cells specific to two immunodominant epitopes derived from the HSV-1 tegument protein VP11/12. Immunization of HLA-DR transgenic mice with a mixture of these two immunodominant CD4+ T cell epitopes induced a robust antiviral CD4+ T cell response in the cornea that was associated with protective immunity against ocular herpes. The emerging concept of developing an asymptomatic herpes vaccine that would boost effector memory CD4+ and CD8+ TEM cell responses is discussed.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/1cg2b9cjTest
-
77دورية أكاديمية
المؤلفون: Kovatchev, Boris, Anderson, Stacey, Raghinaru, Dan, Kudva, Yogish, Laffel, Lori, Levy, Carol, Pinsker, Jordan, Wadwa, R, Buckingham, Bruce, Doyle, Francis, Brown, Sue, Church, Mei, Dadlani, Vikash, Dassau, Eyal, Ekhlaspour, Laya, Forlenza, Gregory, Isganaitis, Elvira, Lam, David, Lum, John, Beck, Roy
المصدر: Diabetes reviews (Alexandria, Va.). 43(3)
مصطلحات موضوعية: Adolescent, Adult, Aged, Biosensing Techniques, Blood Glucose, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1, Female, Humans, Hypoglycemic Agents, Insulin, Insulin Infusion Systems, Insulin, Regular, Human, Male, Middle Aged, Mobile Applications, Pancreas, Artificial, Telemedicine, United States, Young Adult
الوصف: OBJECTIVE: Assess the efficacy of inControl AP, a mobile closed-loop control (CLC) system. RESEARCH DESIGN AND METHODS: This protocol, NCT02985866, is a 3-month parallel-group, multicenter, randomized unblinded trial designed to compare mobile CLC with sensor-augmented pump (SAP) therapy. Eligibility criteria were type 1 diabetes for at least 1 year, use of insulin pumps for at least 6 months, age ≥14 years, and baseline HbA1c
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/6zz540wmTest
-
78دورية أكاديمية
المؤلفون: Joish, Vijay, Zhou, Fang, Preblick, Ronald, Lin, Dee, Deshpande, Maithili, Verma, Sumit, Davies, Michael, Paranjape, Sachin, Pettus, Jeremy
المصدر: Journal of Managed Care and Specialty Pharmacy. 26(3)
مصطلحات موضوعية: Adolescent, Adult, Aged, Cohort Studies, Databases, Factual, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Female, Health Care Costs, Health Resources, Humans, Male, Middle Aged, Retrospective Studies, United States, Young Adult
الوصف: BACKGROUND: Diabetes health care resource utilization (HCRU) studies tend to focus on patients with type 2 diabetes (T2D) or pool patients with T2D and type 1 diabetes (T1D). There is a paucity of recent data on the cost of treating patients with T1D in the United States. OBJECTIVES: To (a) estimate the per-patient per-year (PPPY) HCRU and costs, from a payer perspective, associated with treating U.S. adults with T1D and (b) compare these with the HCRU and costs for patients with T2D. METHODS: This retrospective cohort study used claims data from the Optum Clinformatics database between January 2015 and December 2017. Adults (aged ≥ 18 years) with a diagnosis of T1D were propensity score-matched to adults with T2D. Overall and nondiabetes-related HCRU and costs were assessed for T1D and T2D and compared between the 2 groups. RESULTS: Propensity scores were used to match 10,103 patient pairs from T1D and T2D cohorts (mean ages 54.4 and 56.9 years, respectively). In the T1D cohort, inpatient, emergency department (ED), outpatient, and prescription claims occurred in 14.0%, 17.3%, 85.5%, and 100% of patients, respectively, resulting in a mean total cost of U.S. $18,817 PPPY (diabetes-related = $11,002; nondiabetes-related = $7,816). The T1D cohort had significantly higher mean total costs than the T2D cohort ($18,817 vs. $14,148 PPPY; P < 0.001). When extrapolating these findings to a commercial health plan with 1 million covered lives, the estimated total direct medical costs of T1D would be $103.4 million. CONCLUSIONS: This study showed that the total annual cost of managing an adult with T1D is significantly higher than that of an adult with T2D. Nondiabetes costs accounted for 40% of the total per-patient cost, similar to patients with T2D, confirming that as patients with T1D live longer lives, they may also be at greater risk for cardiometabolic complications. DISCLOSURES: This study was funded by Sanofi U.S. and Lexicon Pharmaceuticals as part of a business partnership in a diabetes program at the time this study was conducted. Joish and Davies are employees and stockholders of Lexicon Pharmaceuticals. Zhou, Preblick, and Paranjape are employees and stockholders of Sanofi. Lin was a postdoctoral fellow at Sanofi through Rutgers University during this project. Deshpande provided consulting services through Communication Symmetry. Verma is an employee of Evidera, which was contracted by Sanofi for work on this study. Pettus is a consultant for Diasome, Insulet, Lexicon, Lilly, Mannkind, Novo Nordisk, Sanofi, and Senseonics.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/204090bkTest
-
79دورية أكاديمية
المؤلفون: Reddam, Aalekhya, Tait, George, Herkert, Nicholas, Hammel, Stephanie C, Stapleton, Heather M, Volz, David C
مصطلحات موضوعية: Transportation, Logistics and Supply Chains, Built Environment and Design, Commerce, Management, Tourism and Services, Adolescent, Adult, Dust, Environmental Exposure, Environmental Monitoring, Esters, Flame Retardants, Humans, Middle Aged, Organophosphates, Phosphates, Transportation, Young Adult, Organophosphate esters, Silicone wristband, Tris(1, 3-dichloro-2-propyl) phosphate, Human exposure, Environmental Sciences
الوصف: Organophosphate esters (OPEs) are a class of semi-volatile organic compounds (SVOCs) used as flame retardants, plasticizers, and anti-foaming agents. Due to stringent flammability standards in vehicles and the ability of OPEs to migrate out of end-use products, elevated concentrations of OPEs have been found in car dust samples around the world. As many residents of Southern California spend a significant amount of time in their vehicles, there is potential for increased exposure to OPEs associated with longer commute times. As approximately 70% of the University of California, Riverside's undergraduate population commutes, the objective of this study was to use silicone wristbands to monitor personal exposure to OPEs and determine if exposure was associated with commute time in a subset of these students. Participants were asked to wear wristbands for five continuous days and complete daily surveys about the amount of time spent commuting. Data were then used to calculate a participant-specific total commute score. Components of Firemaster 550 (triphenyl phosphate, or TPHP, and isopropylated triaryl phosphate isomers) and Firemaster 600 (TPHP and tert-butylated triaryl phosphate isomers) - both widely used commercial flame retardant formulations - were strongly correlated with other OPEs detected within participant wristbands. Moreover, the concentration of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) was significantly correlated with the concentration of several Firemaster 500 components and tris(2-chloroisopropyl) phosphate (TCIPP). Finally, out of all OPEs measured, TDCIPP was significantly and positively correlated with total commute score, indicating that longer commutes are associated with increased human exposure to TDCIPP. Overall, our findings raise concerns about the potential for chronic TDCIPP exposure within vehicles and other forms of transportation, particularly within densely populated and traffic-congested areas such as Southern California.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/6gf7c658Test
-
80دورية أكاديمية
المؤلفون: Xian, Rena R, Xie, Yi, Haley, Lisa M, Yonescu, Raluca, Pallavajjala, Aparna, Pittaluga, Stefania, Jaffe, Elaine S, Duffield, Amy S, McCall, Chad M, Gheith, Shereen MF, Gocke, Christopher D
المصدر: Blood Cancer Journal. 10(6)
مصطلحات موضوعية: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Oncology and Carcinogenesis, Human Genome, Rare Diseases, Genetics, Hematology, Clinical Research, Cancer, Biotechnology, Lymphoma, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, CREB-Binding Protein, Chromosome Deletion, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 16, Female, Humans, Lymphoma, Follicular, Male, Middle Aged, Mutation, Polymorphism, Single Nucleotide, STAT6 Transcription Factor, Translocation, Genetic, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology, Oncology and carcinogenesis
الوصف: The diffuse variant of follicular lymphoma (dFL) is a rare variant of FL lacking t(14;18) that was first described in 2009. In this study, we use a comprehensive approach to define unifying pathologic and genetic features through gold-standard pathologic review, FISH, SNP-microarray, and next-generation sequencing of 16 cases of dFL. We found unique morphologic features, including interstitial sclerosis, microfollicle formation, and rounded nuclear cytology, confirmed absence of t(14;18) and recurrent deletion of 1p36, and showed a novel association with deletion/CN-LOH of 16p13 (inclusive of CREBBP, CIITA, and SOCS1). Mutational profiling demonstrated near-uniform mutations in CREBBP and STAT6, with clonal dominance of CREBBP, among other mutations typical of germinal-center B-cell lymphomas. Frequent CREBBP and CIITA codeletion/mutation suggested a mechanism for immune evasion, while subclonal STAT6 activating mutations with concurrent SOCS1 loss suggested a mechanism of BCL-xL/BCL2L1 upregulation in the absence of BCL2 rearrangements. A review of the literature showed significant enrichment for 16p13 and 1p36 loss/CN-LOH, STAT6 mutation, and CREBBP and STAT6 comutation in dFL, as compared with conventional FL. With this comprehensive approach, our study demonstrates confirmatory and novel genetic associations that can aid in the diagnosis and subclassification of this rare type of lymphoma.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/39n9r2kjTest