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Pauline Funchain

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https://www.readbyqxmd.com/read/30021908/quantitative-spatial-profiling-of-pd-1-pd-l1-interaction-and-hla-dr-ido-1-predicts-improved-outcomes-of-anti-pd-1-therapies-in-metastatic-melanoma
#1
Douglas B Johnson, Jennifer M Bordeaux, Ju-Young Kim, Christine A Vaupel, David L Rimm, Thai H Ho, Richard W Joseph, Adil I Daud, Robert M Conry, Elizabeth M Gaughan, Leonel F Hernandez-Aya, Anastasios Dimou, Pauline Funchain, James W Smithy, John S Witte, Svetlana B McKee, Jennifer Ko, John Wrangle, Bashar Dabbas, Shabnam Tangri, Jelveh Lameh, Jeffrey M Hall, Joseph Markowitz, Justin M Balko, Naveen K Dakappagari
PURPOSE: PD-1/L1 axis-directed therapies produce clinical responses in a subset of patients, therefore, biomarkers of response are needed. We hypothesized quantifying key immunosuppression mechanisms within the tumor microenvironment by multiparameter algorithms would identify strong predictors of anti-PD1 response. METHODS: Pre-treatment tumor biopsies from 166 patients treated with anti-PD-1 across 10 academic cancer centers were fluorescently stained with multiple markers in discovery (n = 24) and validation (n = 142) cohorts...
July 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29764498/talimogene-laherparepvec-combined-with-anti-pd-1-based-immunotherapy-for-unresectable-stage-iii-iv-melanoma-a-case-series
#2
Lillian Sun, Pauline Funchain, Jung Min Song, Patricia Rayman, Charles Tannenbaum, Jennifer Ko, Michael Mcnamara, C Marcela Diaz-Montero, Brian Gastman
BACKGROUND: Talimogene Laherparepvec (T-VEC) is an oncolytic virus approved as an intratumoral therapy for treating unresectable stage IIIB-IV metastatic melanoma. The mechanisms of action for T-VEC and checkpoint inhibitor are highly complementary. Recent studies have shown that combining checkpoint inhibitor therapy with T-VEC injection can lead to improved response rates for stage IIIB-IV melanoma patients. METHODS: We reviewed 10 consecutive cases of stage IIIC to stage IVM1b melanoma patients that received T-VEC plus checkpoint inhibitor(s) therapy (pembrolizumab, ipilimumab/nivolumab, or nivolumab) treated between June 2016 and August 2017 at the Cleveland Clinic with a median follow-up of 7 months (range: 4 to 13 months)...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29548064/using-genomic-sequencing-to-improve-management-in-melanoma
#3
Pauline Funchain, Ahmad A Tarhini
Rapidly advancing genomic sequencing technologies are changing all areas of cancer, from diagnosis to surveillance, and prognostication to treatment. The role of genomic testing in melanoma is expanding, and multiple genomically based tests are available, including somatic tumor sequencing for actionable genetic alterations and tumor mutational burden, prognostic gene expression profiling from tumor tissue, and germline genetic testing from blood. The available testing options have varying levels of supporting data, from robust to preliminary...
March 15, 2018: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/29473999/melanoma-cases-demonstrate-increased-carrier-frequency-of-phenylketonuria-hyperphenylalanemia-mutations
#4
Joshua Arbesman, Sairekha Ravichandran, Pauline Funchain, Cheryl L Thompson
Identifying novel melanoma genetic risk factors informs screening and prevention efforts. Mutations in the phenylalanine hydroxylase gene (the causative gene in phenylketonuria) lead to reduced pigmentation in untreated phenylketonuria patients, and reduced pigmentation is associated with greater melanoma risk. Therefore, we sought to characterize the relationship between phenylketonuria carrier status and melanoma risk. Using National Newborn Screening Reports, we determined the United States phenylketonuria/hyperphenylalanemia carrier frequency in Caucasians to be 1...
July 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29408526/prognostic-value-of-sentinel-lymph-node-biopsy-according-to-breslow-thickness-for-cutaneous-melanoma
#5
Evan Stiegel, David Xiong, Jason Ya, Pauline Funchain, Raymond Isakov, Brian Gastman, Alok Vij
BACKGROUND: Sentinel lymph node (SLN) biopsy is widely performed for melanoma with certain histologic parameters and offers important prognostic and staging information. Breslow thickness (BT) by itself also provides meaningful prognostic information. OBJECTIVE: To evaluate whether SLN status provides prognostic information independent from that which is already provided by BT. METHODS: We conducted a retrospective cohort study of 896 patients who underwent SLN biopsy for primary cutaneous melanoma...
May 2018: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29071693/changing-treatment-paradigms-for-brain-metastases-from-melanoma-part-2-when-and-how-to-use-the-new-systemic-agents
#6
REVIEW
Vyshak Alva Venur, Pauline Funchain, Rupesh Kotecha, Samuel T Chao, Manmeet S Ahluwalia
Until recently, therapeutic strategies for melanoma brain metastases focused on local treatments: surgery, whole-brain radiation therapy, and stereotactic radiosurgery. Historically, systemic therapy had limited utility. Immunotherapeutic drugs, such as anti-cytotoxic T-lymphocyte-associated antigen 4 and anti-programmed death 1 agents, and agents targeting the BRAF-MEK pathway have revolutionized the systemic treatment of melanoma brain metastases. Recent clinical trials of these agents have shown activity against melanoma brain metastases, and they are increasingly being used in clinical practice...
September 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28812301/changing-treatment-paradigms-for-brain-metastases-from-melanoma-part-1-diagnosis-prognosis-symptom-control-and-local-treatment
#7
REVIEW
Vyshak Alva Venur, Pauline Funchain, Rupesh Kotecha, Samuel T Chao, Manmeet S Ahluwalia
Melanoma is the third most common cause of brain metastases, after lung and breast cancer. The management of melanoma brain metastases can be broadly divided into symptom control and therapeutic strategies. Supportive treatments include corticosteroids to reduce peritumoral edema, antiepileptics for seizure control, and medications to preserve cognitive function. Until recently, therapeutic strategies consisted primarily of local treatments, including surgery, whole-brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS)...
August 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28799876/melanoma-brain-metastasis-the-impact-of-stereotactic-radiosurgery-braf-mutational-status-and-targeted-and-or-immune-based-therapies-on-treatment-outcome
#8
Rupesh Kotecha, Jacob A Miller, Vyshak A Venur, Alireza M Mohammadi, Samuel T Chao, John H Suh, Gene H Barnett, Erin S Murphy, Pauline Funchain, Jennifer S Yu, Michael A Vogelbaum, Lilyana Angelov, Manmeet S Ahluwalia
OBJECTIVE The goal of this study was to investigate the impact of stereotactic radiosurgery (SRS), BRAF status, and targeted and immune-based therapies on the recurrence patterns and factors associated with overall survival (OS) among patients with melanoma brain metastasis (MBM). METHODS A total of 366 patients were treated for 1336 MBMs; a lesion-based analysis was performed on 793 SRS lesions. The BRAF status was available for 78 patients: 35 had BRAF mut and 43 had BRAF wild-type ( BRAF-WT) lesions. The Kaplan-Meier method evaluated unadjusted OS; cumulative incidence analysis determined the incidences of local failure (LF), distant failure, and radiation necrosis (RN), with death as a competing risk...
July 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28173873/microbiomic-differences-in-tumor-and-paired-normal-tissue-in-head-and-neck-squamous-cell-carcinomas
#9
Hannah Wang, Pauline Funchain, Gurkan Bebek, Jessica Altemus, Huan Zhang, Farshad Niazi, Charissa Peterson, Walter T Lee, Brian B Burkey, Charis Eng
BACKGROUND: While the role of the gut microbiome in inflammation and colorectal cancers has received much recent attention, there are few data to support an association between the oral microbiome and head and neck squamous cell carcinomas. Prior investigations have been limited to comparisons of microbiota obtained from surface swabs of the oral cavity. This study aims to identify microbiomic differences in paired tumor and non-tumor tissue samples in a large group of 121 patients with head and neck squamous cell carcinomas and correlate these differences with clinical-pathologic features...
February 7, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28053877/metabolomic-analysis-identifies-differentially-produced-oral-metabolites-including-the-oncometabolite-2-hydroxyglutarate-in-patients-with-head-and-neck-squamous-cell-carcinoma
#10
Pranab K Mukherjee, Pauline Funchain, Mauricio Retuerto, Richard J Jurevic, Nicole Fowler, Brian Burkey, Charis Eng, Mahmoud A Ghannoum
BACKGROUND: Metabolomics represents a promising approach for discovering novel targets and biomarkers in head and neck squamous cell carcinoma (HNSCC). Here we used metabolomics to identify oral metabolites associated with HNSCC. METHODS: Tumor and adjacent normal tissue from surgical resections and presurgical oral washes as well as oral washes were collected from healthy participants. Metabolites extractions of these samples were analyzed by liquid chromatography-mass spectroscopy (LC/MS), LC/MS/MS and gas chromatography-MS (GC/MS)...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28025390/prevalence-of-hpv-infection-in-racial-ethnic-subgroups-of-head-and-neck-cancer-patients
#11
Camille Ragin, Jeffrey C Liu, Gieira Jones, Olubunmi Shoyele, Bukola Sowunmi, Rachel Kennett, Harry J M Groen, Denise Gibbs, Elizabeth Blackman, Michael Esan, Margaret S Brandwein, Karthik Devarajan, Francesco Bussu, Rebecca Chernock, Chih-Yen Chien, Marc A Cohen, El-Mofty Samir, Suzuki Mikio, Gypsyamber D'Souza, Pauline Funchain, Charis Eng, Susanne M Gollin, Angela Hong, Yuh-S Jung, Maximilian Krüger, James Lewis, Patrizia Morbini, Santo Landolfo, Massimo Rittà, Jos Straetmans, Krisztina Szarka, Ruth Tachezy, Francis P Worden, Deborah Nelson, Samuel Gathere, Emanuela Taioli
The landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial/ethnic background...
December 26, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27899194/strategies-for-clinical-implementation-of-screening-for-hereditary-cancer-syndromes
#12
REVIEW
Brandie Heald, Jessica Marquard, Pauline Funchain
Hereditary cancer syndromes generally account for 5%-10% of malignancies. While these syndromes are rare, affected patients carry significantly elevated risks of developing cancer, as do their at-risk relatives. Identification of these patients is critical to ensure timely and appropriate genetic testing relevant to cancer patients and their relatives. Several guidelines and tools are available to assist clinicians. Patients suspected to have hereditary cancer syndromes should be offered genetic testing in the setting of genetic counseling by a qualified genetics professional...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/26962171/complete-durable-response-from-carboplatin-and-olaparib-in-a-heavily-pretreated-triple-negative-metastatic-breast-cancer-with-germline-brca2-and-brcaness-mutations
#13
Sanghee Hong, Pauline Funchain, Abdo Haddad, Joseph Crowe, Nancy Dalpiaz, Jame Abraham
No abstract text is available yet for this article.
March 2016: Journal of Oncology Practice
https://www.readbyqxmd.com/read/26553780/prospective-clinical-study-of-precision-oncology-in-solid-tumors
#14
Davendra P S Sohal, Brian I Rini, Alok A Khorana, Robert Dreicer, Jame Abraham, Gary W Procop, Yogen Saunthararajah, Nathan A Pennell, James P Stevenson, Robert Pelley, Bassam Estfan, Dale Shepard, Pauline Funchain, Paul Elson, David J Adelstein, Brian J Bolwell
Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact...
November 9, 2015: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/23731547/hunting-for-cancer-in-the-microbial-jungle
#15
Pauline Funchain, Charis Eng
No abstract text is available yet for this article.
2013: Genome Medicine
https://www.readbyqxmd.com/read/22490388/a-reinvestigation-of-somatic-hypermethylation-at-the-pten-cpg-island-in-cancer-cell-lines
#16
Luke B Hesson, Deborah Packham, Emily Pontzer, Pauline Funchain, Charis Eng, Robyn L Ward
BACKGROUND: PTEN is an important tumour suppressor gene that is mutated in Cowden syndrome as well as various sporadic cancers. CpG island hypermethylation is another route to tumour suppressor gene inactivation, however, the literature regarding PTEN hypermethylation in cancer is controversial. Furthermore, investigation of the methylation status of the PTEN CpG island is challenging due to sequence homology with the PTEN pseudogene, PTENP1. PTEN shares a CpG island promoter with another gene known as KLLN...
2012: Biological Procedures Online
https://www.readbyqxmd.com/read/22180460/microbiomic-subprofiles-and-mdr1-promoter-methylation-in-head-and-neck-squamous-cell-carcinoma
#17
Gurkan Bebek, Kristi L Bennett, Pauline Funchain, Rebecca Campbell, Rahul Seth, Joseph Scharpf, Brian Burkey, Charis Eng
Clinical observations and epidemiologic studies suggest that the incidence of head and neck squamous cell carcinoma (HNSCC) correlates with dental hygiene, implying a role for bacteria-induced inflammation in its pathogenesis. Here we begin to explore the pilot hypothesis that specific microbial populations may contribute to HNSCC pathogenesis via epigenetic modifications in inflammatory- and HNSCC-associated genes. Microbiomic profiling by 16S rRNA sequencing of matched tumor and adjacent normal tissue specimens in 42 individuals with HNSCC demonstrate a significant association of specific bacterial subpopulations with HNSCC over normal tissue (P < 0...
April 1, 2012: Human Molecular Genetics
https://www.readbyqxmd.com/read/21173910/acute-liver-injury-induced-by-weight-loss-herbal-supplements
#18
Gary C Chen, Vivek S Ramanathan, David Law, Pauline Funchain, George C Chen, Samuel French, Boris Shlopov, Viktor Eysselein, David Chung, Sonya Reicher, Binh V Pham
We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss...
November 27, 2010: World Journal of Hepatology
https://www.readbyqxmd.com/read/15659661/mutants-with-temperature-sensitive-defects-in-the-escherichia-coli-mismatch-repair-system-sensitivity-to-mispairs-generated-in-vivo
#19
Esther S Hong, Annie Yeung, Pauline Funchain, Malgorzata M Slupska, Jeffrey H Miller
We have used direct selections to generate large numbers of mutants of Escherichia coli defective in the mismatch repair system and have screened these to identify mutants with temperature-sensitive defects. We detected and sequenced mutations that give rise to temperature-sensitive MutS, MutL, and MutH proteins. One mutation, mutS60, results in almost normal levels of spontaneous mutations at 37 degrees C but above this temperature gives rise to higher and higher levels of mutations, reaching the level of null mutations in mutS at 43 degrees C...
February 2005: Journal of Bacteriology
https://www.readbyqxmd.com/read/15059895/epigenetic-profiling-in-chronic-lymphocytic-leukemia-reveals-novel-methylation-targets
#20
Laura J Rush, Aparna Raval, Pauline Funchain, Amy J Johnson, Lisa Smith, David M Lucas, Melania Bembea, Te-Hui Liu, Nyla A Heerema, Laura Rassenti, Sandya Liyanarachchi, Ramana Davuluri, John C Byrd, Christoph Plass
CpG island methylation is an epigenetic alteration that contributes to tumorigenesis by transcriptional inactivation of genes. Little is known about the overall levels of CpG island methylation in chronic lymphocytic leukemia (CLL). To provide a baseline estimate of global aberrant methylation and identify target sequences for additional investigation, we performed Restriction Landmark Genomic Scanning on 10 CLL samples. Two methylation-sensitive landmark enzymes were used (NotI and AscI), allowing assessment of over 3000 CpG islands in each sample...
April 1, 2004: Cancer Research
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