Medical Specialties Commons^™

Telotristat Ethyl In Carcinoid Syndrome: Safety And Efficacy In The Telecast Phase 3 Trial, Marianne Pavel, David J. Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R. P. Warner, Matthew H. Kulke, Lowell B. Anthony, Pamela L. Kunz, Dieter Hörsch, Martin O Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio Garcia-Carbonero

Internal Medicine Faculty Publications

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥ 4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with < 4 BMs/day on SSAs (or ≥ 1 symptom or ≥ 4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. …

Demographic, Presentation, And Treatment Factors And Racial Disparities In Ovarian Cancer Hospitalization Outcomes, Tomi F. Akinyemiju, Gurudatta Naik, Kemi Ogunsina, Daniel T. Dibaba, Neomi Vin-Raviv

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: This study examines whether racial disparities in hospitalization outcomes persist between African-American and White women with ovarian cancer after matching on demographic, presentation, and treatment factors.

METHODS: Using data from the Nationwide Inpatient Sample database, 5,164 African-American ovarian cancer patients were sequentially matched with White patients on demographic (e.g., age, income), presentation (e.g., stage, comorbidities), and treatment (e.g., surgery, radiation) factors. Racial differences in-hospital length of stay, post-operative complications, and in-hospital mortality were evaluated using conditional logistic regression models.

RESULTS: White ovarian cancer patients had relatively higher odds of post-operative complications when matched on demographics (OR 1.35, 95% CI …

Treatment Options For Primary Cns Lymphoma, Abid Laghari, Syed Ijlal Ahmed, Adnan Jabbar, Muhammad Shahzad Shamim

Section of Haematology/Oncology

Primary CNS lymphoma (PCNSL) is a rare and aggressive brain tumour that is uniformly fatal. The rarity of the disease and the poor response to treatment makes it difficult to reach a consensus with regards to treatment options. In this review, the authors have discussed different treatment modalities used in the management of PCNSL including chemotherapy, surgery and radiation, as well as the results of recent clinical trials on treatment options for PCNSL.

Clinical Audit To Assess Delays In Chemotherapy Administration At Daycare Oncology Center At A Tertiary Care Hospital In Karachi, Pakistan, Arifa Aziz, Zarka Samoon, Mohammad Khurshid, Afsheen Feroz, Nadia Ayoub, Safia Awan, Madhia Beg

Section of Haematology/Oncology

Aim: There were delays reported by patients in chemotherapy administration in daycare oncology. Therefore, we decided to audit all processes which are involved in chemotherapy administration. The objective was to improve our service by decreasing the time between admission and initiation of chemotherapy and identify the reasons for delays.

Materials and Methods: The audit was conducted in three parts. In Review I, audit tool was developed and information documented of 109 patients receiving chemotherapy at daycare center from April 14 to May 13, 2015. Five processes were assessed out of which delay in initial assessment by the nurse was the …

Ferrocenylchalcone-Uracil Conjugates: Synthesis And Cytotoxic Evaluation, Amandeep Singh, Vishu Mehra, Neda Sadeghiani, Saghar Mozaffari, Keykavous Parang, Vipan Kumar

Pharmacy Faculty Articles and Research

Huisgen’s azide-alkyne cycloaddition reaction was employed to synthesize a series of 1H-1,2,3-triazole-tethered uracil-ferrocenyl chalcone conjugates with the aim of evaluating their in vitro anti-proliferative efficacy on human leukemia (CCRF-CEM) and human breast adenocarcinoma (MDA-MB-468) cell lines. Cytotoxic evaluation studies identified a number of synthesized conjugates that inhibited the proliferation of leukemia cancer cells by ~70% after 72 h. The selected synthesized conjugates were found to be significantly less cytotoxic against normal kidney cell line (LLC-PK1) when compared with CCRF-CEM cancer cells.

Resveratrol And Pterostilbene Exhibit Anticancer Properties Involving The Downregulation Of Hpv Oncoprotein E6 In Cervical Cancer Cells, Kaushiki Chatterjee, Dina Alsharif, Christina Mazza, Palwasha Syar, Mohamed Al Sharif, Jimmie E. Fata

Publications and Research

Cervical cancer is one of the most common cancers in women living in developing countries. Due to a lack of affordable effective therapy, research into alternative anticancer compounds with low toxicity such as dietary polyphenols has continued. Our aim is to determine whether two structurally similar plant polyphenols, resveratrol and pterostilbene, exhibit anticancer and anti-HPV (Human papillomavirus) activity against cervical cancer cells. To determine anticancer activity, extensive in vitro analyses were performed. Anti-HPV activity, through measuring E6 protein levels, subsequent downstream p53 effects, and caspase-3 activation, were studied to understand a possible mechanism of action. Both polyphenols are effective agents …

A Lin28b Tumor-Specific Transcript In Cancer, Weijie Guo, Zhixiang Hu, Yichao Bao, Yuchen Li, Shengli Li, Qiupeng Zheng, Dongbin Lyu, Di Chen, Tao Yu, Yan Li, Xiaodong Zhu, Jie Ding, Yingjun Zhao, Xianghuo He, Shenglin Huang

Markey Cancer Center Faculty Publications

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer …

Targeting Cdk6 And Bcl2 Exploits The "Myb Addiction" Of Ph+ Acute Lymphoblastic Leukemia, Marco De Dominici, Patrizia Porazzi, Angela Rachele Soliera, Samanta A. Mariani, Sankar Addya, Paolo Fortina, Luke F. Peterson, Orietta Spinelli, Alessandro Rambaldi, Giovanni Martinelli, Anna Ferrari, Ilaria Iacobucci, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph^þ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1–dependent and –independent mechanisms. Newly developed TKI can target Ph^þ ALL cells with BCR-ABL1–dependent resistance; however, overcoming BCR-ABL1–independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Ph^þ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced …

Downregulation Of Srebp Inhibits Tumor Growth And Initiation By Altering Cellular Metabolism In Colon Cancer, Yang-An Wen, Xiaopeng Xiong, Yekaterina Y. Zaytseva, Dana L. Napier, Emma Vallee, Austin T. Li, Chi Wang, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Markey Cancer Center Faculty Publications

Sterol regulatory element-binding proteins (SREBPs) belong to a family of transcription factors that regulate the expression of genes required for the synthesis of fatty acids and cholesterol. Three SREBP isoforms, SREBP1a, SREBP1c, and SREBP2, have been identified in mammalian cells. SREBP1a and SREBP1c are derived from a single gene through the use of alternative transcription start sites. Here we investigated the role of SREBP-mediated lipogenesis in regulating tumor growth and initiation in colon cancer. Knockdown of either SREBP1 or SREBP2 decreased levels of fatty acids as a result of decreased expression of SREBP target genes required for lipid biosynthesis in …

Global Survey Of Clinical Oncology Workforce, Aju Mathew

Internal Medicine Faculty Publications

A lack of well-trained clinical oncologists can result in significant cancer health disparities. The magnitude of this problem around the world is poorly described in the literature. A comprehensive global survey of the clinical oncology workforce was conducted. Data on the number of clinical oncologists in 93 countries were obtained from 30 references. The mortality-to-incidence ratio was estimated by using data on incidence and mortality rates from the GLOBOCAN 2012 database; the ratio was > 70% in 26 countries (28%), which included 21 countries in Africa (66%) and five countries in Asia (26%). Eight countries had no clinical oncologist available to …

Oncolog, Volume 63, Number 02, February 2018, Sarah Bronson, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Radiation Therapy for Liver Cancer: Clinical trials expand treatment options for patients with primary liver cancer
• Proton Therapy for Breast Cancer May Avoid Heart Damage: Trial compares cardiotoxicity of proton-and photon-based radiation therapy to the breast/chest wall and lymph nodes
• New targeted Therapies for Leukemia: New treatments target CD123, BCL2 proteins in acute myelogenous leukemia, blastic plasmacytoid dendritic cell neoplasm
• HOUSE CALL: Supportive Care for Cancer Patients- Supportive care treats the whole patient, not just the cancer

Neurotensin Receptor 3/Sortilin Contributes To Tumorigenesis Of Neuroendocrine Tumors Through Augmentation Of Cell Adhesion And Migration, Ji Tae Kim, Dana L. Napier, Heidi L. Weiss, Eun Y. Lee, Courtney M. Townsend, B. Mark Evers

Markey Cancer Center Faculty Publications

Neurotensin (NTS), a 13–amino acid peptide which is distributed predominantly along gastrointestinal tract, has multiple physiologic and pathologic functions, and its effects are mediated by three distinct NTS receptors (NTSRs). Overexpression and activation of NTS signaling components, especially NTS and/or NTSR1, are closely linked with cancer progression and metastasis in various types of cancers including neuroendocrine tumors (NETs). Although deregulation of NTSR3/sortilin has been implicated in a variety of human diseases, the expression and role of NTSR3/sortilin in NETs have not been elucidated. In this study, we investigated the expression and oncogenic effect of NTSR3/sortilin in NETs. Increased protein levels …

Cd20 Expression And Effects On Outcome Of Relapsed/ Refractory Diffuse Large B Cell Lymphoma After Treatment With Rituximab, Afshan Asghar Rasheed, Adeel Samad, Ahmed Raheem, Samina Ismail Hirani, Shabbir Shabbir- Moosajee

Section of Haematology/Oncology

Introduction: Down regulation of CD20 expression has been reported in diffuse large B cell lymphoma (DLBCL)). Therefore, it is important to determine whether chemotherapy with rituximab induces CD20 down regulation and effects survival. Objectives: To determine the incidence of down regulation of CD20 expression in relapsed DLBCL after treatment with rituximab and to compare outcomes and assess pattern of relapse between CD20 negative and CD20 positive cases. Methodology: We retrospectively reviewed patients with relapsed DLBCL who received rituximab in the first line setting at Aga Khan University Hospital between January 2007 and December 2014. Data were recorded on predesigned questionnaires, …

Amine Containing Analogs Of Sulindac For Cancer Prevention, Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds

Pharmaceutical Sciences Faculty Publications

Background:

Sulindac belongs to the chemically diverse family of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) that effectively prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA), an amide analog of sulindac sulfide, shows insignificant COX-related activity and toxicity while enhancing anticancer activity in vitro and demonstrating in vivo xenograft activity.

Objective:

Develop structure-activity relationships in the sulindac amine series and identify analogs with promising anticancer activities.

Method:

A series of sulindac amine analogs were designed and synthesized and then further modified in a “libraries from libraries” approach to produce amide, sulfonamide and N,N-disubstituted …

Ependymomas Overexpress Chemoresistance And Dna Repair-Related Proteins., Sherise D Ferguson, Shouhao Zhou, Joanne Xiu, Yuuri Hashimoto, Nader Sanai, Lyndon Kim, Santosh Kesari, John De Groot, David Spetzler, Amy B Heimberger

Articles, Abstracts, and Reports

Background: After surgery and radiation, treatment options for ependymoma are few making recurrence a challenging issue. Specifically, the efficacy of chemotherapy at recurrence is limited. We performed molecular profiling on a cohort of ependymoma cases in order to uncover therapeutic targets and to elucidate the molecular mechanisms contributing to treatment resistance.

Results: This ependymoma cohort showed minimal alterations in gene amplifications and mutations but had high expression rates of DNA synthesis and repair enzymes such as RRM1 (47%), ERCC1 (48%), TOPO1 (62%) and class III β-tublin (TUBB3) (57%), which are also all associated with chemoresistance. This cohort also had high …

Galectin - Method For Enhancing Specific Immunotherapies In Cancer Treatment, Peter G. Traber, William L. Redmond, Eliezer Zomer, Anatole Klyosov, Stephanie N. Linch

Technology Transfer - Patents

Methods and compositions of the invention relate to the enhancement of specific immunotherapies in cancer treatment. In particular, aspects of the invention relate to novel approaches to boost immune function using a complex carbohydrate pharmaceutical compound alone or in combination with other targeted immunotherapy to increase the efficacy of immunotherapy of cancer.

Mammographic Breast Density And Breast Cancer Molecular Subtypes: The Kenyan-African Aspect, Asim Jamal, Maeve Mullooly, Shahin Sayed, Rose Ndumia, Innocent Abayo, James Orwa, Ronald Wasike, Zahir Moloo, Gretchen L. Gierach

Internal Medicine, East Africa

Introduction: Data examiningmammographic breast density (MBD) among patients in Sub-Saharan Africa are sparse.We evaluated how MBD relates to breast cancer characteristics in Kenyan women undergoing diagnostic mammography.

Methods: This crosssectional study included women with pathologically confirmed breast cancers (𝑛 = 123). Pretreatment mammograms of the unaffectedbreast were assessed to estimate absolute dense area (cm2), nondense area (cm2), and percent density (PD). Relationships between density measurements and clinical characteristics were evaluated using analysis of covariance.

Results: Median PD and dense area were 24.9% and 85.3 cm2. Higher PD and dense area were observed in younger women (𝑃 < 0.01). Higher dense and nondense areas were observed in obese women (𝑃-trend < 0.01). Estrogen receptor (ER) positive patients (73%) had higher PD and dense area than ER-negative patients (𝑃 ≤ 0.02). Triple negative breast cancer (TNBC) patients (17%) had lower PD and dense area (𝑃 ≤ 0.01) compared with non-TNBCs. No associations were observed between MBD and tumor size and grade.

Conclusions: Our findings show …

Emotion Regulation And Positive Affect In The Context Of Salivary Alpha-Amylase Response To Pain In Children With Cancer, Brooke N. Jenkins, Douglas A. Granger, Ryan J. Roemer, Ariana Martinez, Tara K. Torres, Michelle A. Fortier

Psychology Faculty Articles and Research

Background

Children with cancer routinely undergo painful medical procedures invoking strong physiological stress responses. Resilience to this pain may be conferred through resources such as emotion regulation strategies and positive affect.

Procedure

This study measured dispositional positive affect in children with cancer (N = 73) and randomly assigned participants to one of three emotion regulation strategy conditions (distraction, reappraisal, or reassurance). Children applied their assigned strategy during an experimental pain procedure (the cold pressor task [CPT]) and provided saliva samples before, immediately after, and 15 min after the CPT. Saliva samples were later assayed for salivary alpha amylase (sAA)—a surrogate …

Liposomal Tricurin, A Synergistic Combination Of Curcumin, Epicatechin Gallate And Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, And Eliminates Glioblastoma (Gbm) And Gbm Stem Cells, Sumit Mukherjee, Juliet N. E. Baidoo, Samay Sampat, Andrew Manusco, Lovena David, Leah S. Cohen, Shuiqin Zhou, Probal Banerjee

Publications and Research

Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12–15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (M): 32:8:100 (termed 32 M+ TriCurin). We have now prepared liposomal TriCurin (TrLp) and demonstrated …

Implementation Of A Low-Cost Unna Boot Alternative As Adjunctive Treatment For Kaposi Sarcoma, Alexander Robert Mills, Edith Tonui, Sonak Pastakia, Rakhi Karwa, Phelix Were

Engagement & Service-Learning Summit

There are 6 million people living with HIV; 70% reside in Sub-Saharan Africa (SSA). Furthermore, 1.1 million deaths occur due to opportunistic infections (OIs) that can be minimized with antiretroviral therapy. In Kenya, Kaposi Sarcoma (KS) is an especially debilitating OI that presents with dermatologic lesions; magnifying the stigma that patients with HIV face physically and psychosocially. Dermatology research is underway to determine the effectiveness of an unna boot (medicated, layered compression dressing) to speed the healing of these lesions with anecdotal success. Commercially available unna boot products are too expensive and not readily available in SSA. Clinicians from Purdue …

Beta-Catenin Cleavage Enhances Transcriptional Activation, Tatiana Goretsky, Emily M. Bradford, Qing Ye, Olivia F. Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C. Keller, Preetika Sinh, Josep M. Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat⁵⁵²). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat⁵⁵², increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat⁵⁵² in the nucleus of inflamed and …

Surgical Interventions For Advanced Parameningeal Rhabdomyosarcoma Of Children And Adolescents., Paul J Choi, Joe Iwanaga, R Shane Tubbs, Emre Yilmaz

Articles, Abstracts, and Reports

Owing to its rarity, rhabdomyosarcoma of the head and neck (HNRMS) has seldom been discussed in the literature. As most of the data is based only on the retrospective experiences of tertiary healthcare centers, there are difficulties in formulating a standard treatment protocol. Moreover, the disease is poorly understood at its pathological, genetic, and molecular levels. For instance, 20% of all histological assessment is inaccurate; even an experienced pathologist can confuse rhabdomyosarcoma (RMS) with neuroblastoma, Ewing's sarcoma, and lymphoma. RMS can occur sporadically or in association with genetic syndromes associated with predisposition to other cancers such as Li-Fraumeni syndrome and …

A Plasma Telomeric Cell-Free Dna Level In Unaffected Women With Brca1 Or/And Brca2 Mutations: A Pilot Study, Shatovisha Dey, Natascia Marino, Kanokwan Bishop, Paige N. Dahlgren, Aditi Shendre, Anna Maria Storniolo, Chunyan He, Hiromi Tanaka

Internal Medicine Faculty Publications

Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 mutation with age-matched controls …

An Intracellular Activation Of Smoothened That Is Independent Of Hedgehog Stimulation In Drosophila, Kai Jiang, Yajuan Liu, Jie Zhang, Jianhang Jia

Markey Cancer Center Faculty Publications

Smoothened (Smo), a GPCR family protein, plays a critical role in the reception and transduction of Hedgehog (Hh) signal. Smo is phosphorylated and activated on the cell surface; however, it is unknown whether Smo can be intracellularly activated. Here, we demonstrate that inactivation of the ESCRT-III causes dramatic accumulation of Smo in the ESCRT-III/MVB compartment, and subsequent activation of Hh signaling. In contrast, inactivation of ESCRTs 0–II induces mild Smo accumulation in the ESCRT-III/MVB compartment. We provide evidence that Kurtz (Krz), the Drosophila β-arrestin2, acts in parallel with the ESCRTs 0-II pathway to sort Smo to the multivesicular bodies and …

Erk-Mediated Phosphorylation Regulates Sox10 Sumoylation And Targets Expression In Mutant Braf Melanoma., Shujun Han, Yibo Ren, Wangxiao He, Huadong Liu, Zhe Zhi, Xinliang Zhu, Tielin Yang, Yu Rong, Bohan Ma, Timothy J. Purwin, Zhenlin Ouyang, Caixia Li, Xun Wang, Xueqiang Wang, Huizi Yang, Yan Zheng, Andrew E. Aplin, Jiankang Liu, Yongping Shao

Department of Cancer Biology Faculty Papers

In human mutant BRAF melanoma cells, the stemness transcription factor FOXD3 is rapidly induced by inhibition of ERK1/2 signaling and mediates adaptive resistance to RAF inhibitors. However, the mechanism underlying ERK signaling control of FOXD3 expression remains unknown. Here we show that SOX10 is both necessary and sufficient for RAF inhibitor-induced expression of FOXD3 in mutant BRAF melanoma cells. SOX10 activates the transcription of FOXD3 by binding to a regulatory element in FOXD3 promoter. Phosphorylation of SOX10 by ERK inhibits its transcription activity toward multiple target genes by interfering with the sumoylation of SOX10 at K55, which is essential for …

Differential Impact Of Rb Status On E2f1 Reprogramming In Human Cancer., Christopher Mcnair, Kexin Xu, Amy C. Mandigo, Matteo Benelli, Benjamin E. Leiby, Daniel Rodrigues, Johan Lindberg, Henrik Gronberg, Mateus Crespo, Bram De Laere, Luc Dirix, Tapio Visakorpi, Fugen Li, Felix Y. Feng, Johann De Bono, Francesca Demichelis, Mark A. Rubin, Myles Brown, Karen E. Knudsen

Department of Cancer Biology Faculty Papers

The tumor suppressor protein retinoblastoma (RB) is mechanistically linked to suppression of transcription factor E2F1-mediated cell cycle regulation. For multiple tumor types, loss of RB function is associated with poor clinical outcome. RB action is abrogated either by direct depletion or through inactivation of RB function; however, the basis for this selectivity is unknown. Here, analysis of tumor samples and cell-free DNA from patients with advanced prostate cancer showed that direct RB loss was the preferred pathway of disruption in human disease. While RB loss was associated with lethal disease, RB-deficient tumors had no proliferative advantage and exhibited downstream effects …

Economic Evaluation Of Patient Navigation Programs In Colorectal Cancer Care, A Systematic Review., C Gervès-Pinquié, A Girault, S Phillips, S Raskin, Mandi Pratt-Chapman

GW Cancer Institute

Patient navigation has expanded as a promising approach to improve cancer care coordination and patient adherence. This paper addresses the need to identify the evidence on the economic impact of patient navigation in colorectal cancer, following the Health Economic Evaluation Publication Guidelines. Articles indexed in Medline, Cochrane, CINAHL, and Web of Science between January 2000 and March 2017 were analyzed. We conducted a systematic review of the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality assessment of the included studies was based on the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Inclusion criteria …

Mutation Patterns Identify Adult Patients With De Novo Acute Myeloid Leukemia Aged 60 Years Or Older Who Respond Favorably To Standard Chemotherapy: An Analysis Of Alliance Studies, A. K. Eisfeld, J. Kohlschmidt, K. Mrózek, J. S. Blachly, C. J. Walker, D. Nicolet, S. Orwick, S. E. Maharry, J. E. Kolitz, C. D. Bloomfield, +6 Additional Authors

Journal Articles

© 2018 Macmillan Publishers Limited, part of Springer Nature. Thus far, only 5-15% of AML patients aged ≥60 years are cured with chemotherapy. Identification of patients who are less (more) likely to respond to standard chemotherapy might enable early risk stratification toward alternative treatment regimens. We used a next-generation sequencing panel of 80 cancer- and/or leukemia-associated genes to profile molecularly 423 older patients with de novo AML. Using variables identified in multivariable models and co-occurring mutations in NPM1-mutated AML, we classified the patients into good-, intermediate-, and poor-risk groups for complete remission (CR) attainment, disease-free (DFS), and overall survival (OS). …

Oral Curcumin For Radiation Dermatitis: A Urcc Ncorp Study Of 686 Breast Cancer Patients, J. R. Wolf, C. E. Heckler, J. J. Guido, A. R. Peoples, J. S. Gewandter, M. Ling, V. P. Vinciguerra, T. Anderson, L. Evans, G. R. Morrow, +2 Additional Authors

Journal Articles

No abstract provided.

Nf1 Mutations Are Recurrent In Adult Acute Myeloid Leukemia And Confer Poor Outcome, A. K. Eisfeld, J. Kohlschmidt, K. Mrózek, A. Mims, C. J. Walker, J. S. Blachly, D. Nicolet, S. Orwick, J. E. Kolitz, C. D. Bloomfield, +7 Additional Authors

Journal Articles

© 2018 Macmillan Publishers Limited, part of Springer Nature Targeted mutation assessment of 81 genes in 1021 adults with de novo acute myeloid leukemia (AML) identified recurrent mutations in the neurofibromin 1 (NF1) gene in 52 (5.1%) patients, including 36 (5.2%) younger and 16 (4.8%) older patients, which suggests NF1 belongs to the 20 most frequently mutated genes in adult AML. NF1 mutations were found throughout the gene, and comprised missense, frameshift, and nonsense mutations. One mutation hotspot, at amino acid threonine 676 (Thr676), was found in 27% of AML patients with NF1 mutations. NF1-mutated patients belonged more often to …