tbuckley/cabot-search huggingface dataset:
Abstract 2022: Twist1 regulates UVB-induced epidermal cell proliferation in non-melanoma skin cancer
Authors: Jaya Srivastava, Okkyung Rho, John DiGiovanni.
Journal: Cancer Research (2016)

Abstract Nonmelanoma skin cancer (NMSC) is the most common cancer and consists of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). SCC metastases account for up to 20% of all deaths from skin cancer. The major risk factor for the development of NMSC is solar ultraviolet radiation (UV). UVA and UVB both function as initiators and promoters in carcinogenesis and possess immunosuppressive activity. Given the prevalence of this disease, there remains a pressing need for the development of novel prevention and treatment strategies for NMSC. In a recent study (Srivastava et al. 2015. Mol. Carcinog. doi:10.1002/mc.22335), we evaluated the effect of Twist1, a transcription factor that is known to play a role in tumor progression, during epithelial carcinogenesis. Using the two-stage chemical carcinogenesis model, we identified that BK5.Cre x Twist1flox/flox mice, which have a keratinocyte-specific Twist1 knockout (Twist1 KO), developed significantly reduced numbers of papillomas (70% reduction) and SCCs (75% reduction) as well as delayed tumor latency compared to wild-type (WT) mice. Twist1 KO mice also exhibited significantly reduced epidermal proliferation in response to chemical promotion that correlated with reduced levels of cell cycle regulators and increased levels of p53 and p21. In further studies, we have begun analyzing the effects of UVB irradiation in Twist1 KO mice. Specifically, Twist1 KO mice exhibited heightened sensitivity to UVB-induced apoptosis and decreased epidermal proliferation as compared to similarly exposed WT mice. In addition, the accumulation of mast cells in the skin was significantly decreased in Twist1 KO mice as compared to WT mice. Further preliminary experiments showed that the protein expression levels of c-Myc, phospho-p65 (S536) and phospho-p50 (S337) decreased following UVB irradiation whereas levels of the cell cycle inhibitors p21 and p27 exhibited an increased expression in Twist1 KO mice as compared to WT mice. Further experiments have suggested that Twist1 may play a pivotal role in the proliferation/migration of bulge region keratinocyte stem cells (KSCs) following exposure to UVB. These and other results from ongoing experiments will be presented. Collectively, these findings suggest that Twist1 may have a novel role in UVB-induced epithelial carcinogenesis by regulating proliferation and migration of keratinocytes and KSCs. Research supported by CPRIT RP150346, CPRIT RP140108, and NIH T32 ES007247. Citation Format: Jaya Srivastava, Okkyung Rho, John DiGiovanni. Twist1 regulates UVB-induced epidermal cell proliferation in non-melanoma skin cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2022.
Abstract 1227: New small molecules targeting MYC:MAX interactions that inhibits tumor cell growth in a MYC-dependent manner
Authors: Alina Castell, Karin Ridderstråle, Qinzi Yan, Fan Zhang, Per Hydbring, Marcela Franco, Jacob Goodwin, Inga Müller, Siti Mariam Zakaria, Lars Johansson, Lars-Gunnar Larsson
Journal: Cancer Research (2016)

Abstract Deregulated expression of MYC family oncogenes MYC, MYCN and MYCL (here collectively referred to as MYC) occurs in many types of human tumors, and is often associated with aggressive tumor development and poor prognosis. In mouse tumor models, inactivation of MYC often leads to tumor regression with well-tolerated side effects, suggesting that MYC is a potential and suitable target for anti-cancer therapy. At present there are no drugs targeting MYC in the clinic, and transcription factors like MYC are considered difficult to target. However, MYC function is strictly dependent on interaction with cofactors, and targeting such interaction may be a plausible way to combat Myc. We have used cell-based screens utilizing Bimolecular Fluorescence Complementation (BiFC) and split Gaussia luciferase (G-Luc) to identify small molecule inhibitors of the interaction between MYC and its essential partner MAX. Several potent MYC:MAX interaction inhibitors have been identified in these screens and have been validated by other protein-protein interactions (PPI) assays such as in situ Proximity Ligation Assay (isPLA), Fluorescence Resonance Energy Transfer (FRET), Surface Plasmon Resonance (SPR) and coimmunoprecipitations. In general the identified molecules fall into two categories: those that inhibit MYC:MAX interactions not only in cells but also in vitro using purified MYC and MAX, and those that inhibit the interaction in cells but not in vitro, suggesting an indirect mode of action. Molecules of both categories inhibit cell growth and viability of a variety of tumor cells in culture with high efficacy in a MYC-dependent manner. So far, one of the molecules have been utilized for cancer treatment in mouse tumor models and found to significantly inhibit tumor growth and improve survival. These molecules have the potential to become important tools in the studies of MYC function in cells and in vivo as well as potentially basis for drug development for treatment of MYC-driven tumors. We have thus provided proof of principle that our screening systems are able to identify potent PPI inhibitors and we are at present setting up similar systems to screen for inhibitors of other MYC:cofactor interactions of relevance for specific tumor types. Citation Format: Alina Castell, Karin Ridderstråle, Qinzi Yan, Fan Zhang, Per Hydbring, Marcela Franco, Jacob Goodwin, Inga Müller, Siti Mariam Zakaria, Lars Johansson, Lars-Gunnar Larsson. New small molecules targeting MYC:MAX interactions that inhibits tumor cell growth in a MYC-dependent manner. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1227.
Longitudinal Erythronychia of the Fingernail
Authors: Shari R. Lipner, Richard K. Scher
Journal: JAMA Dermatology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Abstract 1993: IL-18 induces an anti-apoptotic effect through stabilizing COX-2 mRNA expression in leukemia
Authors: Yu Yi Chu, Chiung Yuan KO, Ju Ming Wang
Journal: Cancer Research (2016)

Abstract Leukemia is a cancer of bone marrow or blood cells. The acute myeloid leukemia (AML) is a common subtype occurred in adults to result in death. Forcing malignant cells to undergo differentiation instead of killing cancer cells is one of AML therapeutic strategy. However, the AML patients with poor outcome due to drug resistance is still a challenge. In this study, the abundances of the pro-inflammatory cytokine IL-18 and its receptor (IL-18R) were found to be correlated with the occurrence of drug resistance in AML patients. Importantly, we found that IL-18 induced an anti-apoptotic effect on U937 and THP-1 cells. Cyclooxygenase 2 (COX-2) has been suggested to have an anti-apoptotic role in chemo-resistant cancer cells. IL-18 increased COX-2 expression through post-transcriptional regulation in differentiated U937 cells. We found that two RNA binding proteins, HuR and IMP-3, stabilized COX-2 mRNA expression. In addition, IL-18 induced their interaction and facilitated this complex shuttle from nucleus to cytoplasm. Subsequently, HuR and IMP-3 bound to COX-2 mRNA 3’UTR. Two chemical inhibitors of JNK and ERK1/2 attenuated IL-18-enhanced COX-2 transcripts and the shuttle of HuR from nucleus to cytoplasm. These results suggested that IL-18 stabilized COX-2 mRNA through the JNK- and/or ERK1/2-regulated HuR nucleocytoplasmic shuttling and contributed to an anti-apoptotic effect in AML. Citation Format: Yu Yi Chu, Chiung Yuan KO, Ju Ming Wang. IL-18 induces an anti-apoptotic effect through stabilizing COX-2 mRNA expression in leukemia. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1993.
Circadian Rhythm Disruption Promotes Lung Tumorigenesis
Authors: Thales Papagiannakopoulos, Matthew R. Bauer, Shawn M. Davidson, Megan Heimann, Lakshmipriya Subbaraj, Arjun Bhutkar, Jordan Bartlebaugh, Matthew G. Vander Heiden, Tyler Jacks
Journal: Cell Metabolism (2016)
ARCII: Nelfinavir, a hypoxia-modifying agent, in combination with chemoradiotherapy (CRT) in locally-advanced pancreatic cancer (LAPC)–Mechanism and clinical outcomes.
Authors: James Matthew Wilson, Susan J. Dutton, Sara Lyons Hackett, Lisa Durrant, Kwun-Ye Chu, Cynthia Eccles, Aswin George Abraham, Eric O'Neill, Mike Partridge, Maria A Hawkins, William Gillies McKenna, Tim Maughan, Thomas B Brunner, Somnath Mukherjee
Journal: Journal of Clinical Oncology (2015)

e15279 Background: In LAPC, additional benefit of CRT over chemotherapy is uncertain. Optimising local therapy for a subset that never develops distant disease may prolong survival. Nelfinavir is thought to enhance radiosensitivity through hypoxia reduction by increasing tumour blood flow. Methods: A non-randomised, single centre phase II study, in FDG-PET-selectedpatients withhistologically proven LAPC. CRT consisted of: nelfinavir 1250 mg bd (days -3 to 45); gemcitabine 300 mg/m2 & cisplatin 30 mg/m2 (days 2, 9, 23 & 30); concurrent radiotherapy: 59.4 Gy/33# to primary tumour, 50.4 Gy/28# to regional nodes. Adjuvant gemcitabine was given for 6 months. Primary endpoint: 1 year overall survival (OS); secondary endpoints included: toxicity, response rate, resectability, median progression free survival (PFS), OS and local PFS. 6 patients had sequential dynamic 18fluoromisonidazole PET (FMISO-PET) and perfusion CT (pCT) before and after 6-7 days of nelfinavir (given from day -8). Results: 23 patients entered between Feb 2010-July2014. The trial was stopped because of unavailability of nelfinavir in Europe. 3 patients did not complete treatment (1 each of PE, biliary sepsis, stroke). Common G3/4 toxicities: thrombocytopenia/leukopenia (both 35%), diarrhoea (17%), nausea/vomiting (17%), fatigue (13%). 1 yr and median OS: 76.7% (95% CI 52.8-89.6) and 17.4 months (95% CI 12.7-22.8) respectively. 1 yr PFS and Local PFS: 36.8% (16.5-57.5) and 52.9% (95% CI 25.2-74.4) respectively. Mean FDG SUVmax reduction was 39% (p < 0.001) and was ≥60% in 29% of patients. 2 patients became resectable. 4/6 patients had reduced FMISO retention and increased pCT derived blood flow (BF) post-nelfinavir. Mean change in FMISO-k3 (2 tissue compartmental model) -50.3% vs 6% and BF 20.1 vs -7.1% in responders vs non-responders. 8/13 demonstrated a reduction in pAKT in peripheral blood mononuclear cells. Conclusions: Nelfinavir with CRT is well tolerated with promising outcomes, as these patients were not pre-selected through induction chemotherapy. Modulation of hypoxia & BF by nelfinavir was demonstrated. A randomised phase II study, SCALOP2, opens in 2015. Clinical trial information: 2008-006302-42.
Phase I study of intravenous Seneca Valley virus (NTX-010), a replication competent oncolytic virus, in patients with neuroendocrine (NE) cancers
Authors: C. M. Rudin, N. Senzer, J. Stephenson, D. Loesch, K. Burroughs, S. R. Police, P. Hallenbeck
Journal: Journal of Clinical Oncology (2009)

4629 Background: NTX-010 is a naturally occurring replication competent picornavirus with potent and selective tropism for human NE tumors, including small cell cancers and carcinoid. NTX-010 elicts rapid cytolysis in vitro and durable responses following IV dosing in multiple xenograft models. Methods: A first-in-human phase I study of IV NTX-010 was conducted across 5 log-increment dose cohorts from 10 7 vp/kg to 10 11 vp/kg, in patients with NE cancers. Study endpoints included toxicity assessment, response assessment, evaluation of viral titers and clearance in blood, sputum, nasal swabs, urine, and stool, and assessment of neutralizing antibody (Ab) development. Results: 30 patients were treated (6 small cell, 24 carcinoid-type). All small cell patients were heavily pretreated (&gt; third line) and received 10 7 vp/kg. In these patients, median PFS was 1.2 months and median OS was 4.1 months, including 1 long term (16 month +) survivor with prolonged SD after progressing through prior therapies. Carcinoid patients in cohorts 1–4 have 70% SD rate and median PFS of 5.4 months (95% CI 3.6 to NE); median OS has not been reached. Cohort 5, a 12 patient expansion cohort at 10 11 vp/kg restricted to carcinoid, is still being monitored and shows promising antitumor activity including improvement in carcinoid syndrome symptoms, decline in 5HIAA and other serum markers, minor responses by CT scan, and an objective PET response (&gt;50% decrease in SUV). There were no DLTs in any cohort. Evidence of intratumoral viral replication includes delayed kinetics in serum viral titer, post-infusion serum titers greater then the dose administered and positive immunohistochemistry and/or RT-PCR signal for viral antigens in tumor mass despite Ab production. Viral clearance was documented in all subjects and correlated temporally with development of antiviral Ab. Conclusions: NTX-010 is the first picornavirus to be evaluated as an anticancer therapeutic. A single IV dose of 10 11 vp/kg of NTX-010 is safe, has predictable viral kinetics, and shows promising activity against NE tumors. Phase II testing of this novel agent either as a single agent or in combination with standard cytotoxic therapies is warranted. [Table: see text]
Abstract 4513: A prognostic model for pulmonary carcinoid tumors based on large chromosomal alterations
Authors: Konstantinos Leventakos, Aaron S. Mansfield, Stephen J. Murphy, Sarah H. Johnson, Sarah E. Kerr, Marie Christine Aubry, George Vasmatzis, Julian R. Molina
Journal: Cancer Research (2016)

Abstract PURPOSE: Previous mutational analyses have failed to identify a predictive or prognostic marker for pulmonary carcinoid tumors (PCT). The heterogeneity of PCTs coupled with a lack of detailed information about the tumor biology, impedes patient stratification into groups based on tumor phenotypes or treatment response. We sought to use high-throughput next-generation sequencing to improve prognostication. METHODS: We stratified 37 patients with resected PCTs as low risk (n = 17) and high risk (n = 20) based on a 5 year long follow up for recurrence. Patients with no recurrence within 5 years from initial treatment were deemed low risk. Macrodissection was followed by genomic DNA isolation and next-generation sequencing was performed using an Illumina Mate Pair library protocol. Sequence reads were mapped to the human genome, and primers spanning the fusion junctions were used for validation polymerase chain reaction. RESULTS: Carcinoids commonly harbor rearrangements (median 3.5, range 1-167). Large chromosomal gains or losses were found in 24 of the cases (64.8%). We developed a prognostic score that included the total amount of genetic alterations (deletions and translocations). ROC analysis revealed an AUC of 0.76. High risk patients had a mean score of 20 and low risk patients had a mean score of 5.45 (p value = 0.03, Welch Two Sample t-test). Further analysis of the specific genetic alterations harbored by high and low risk PCTs and correlation with the pathologic and immunohistochemical information is currently underway. CONCLUSION: Large chromosomal rearrangements and aneuploidy portend a poor prognosis for patients with PCTs. Mate Pair sequencing of PCTs provides valuable prognostic information for this highly heterogeneous group of cancers. Citation Format: Konstantinos Leventakos, Aaron S. Mansfield, Stephen J. Murphy, Sarah H. Johnson, Sarah E. Kerr, Marie Christine Aubry, George Vasmatzis, Julian R. Molina. A prognostic model for pulmonary carcinoid tumors based on large chromosomal alterations. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4513.
Retrospective study of irinotecan plus cisplatin induction followed by concurrent thoracic irradiation with irinotecan plus cisplatin chemotherapy for limited-disease small cell lung cancer.
Authors: J. Jeong, J. Sung, H. Pyo, K. Cho, H. Kim, J. Han, T. Yun, G. Lee, J. Lee
Journal: Journal of Clinical Oncology (2010)

7053 Background: Japanses Clinical Oncology Group (JCOG) 9104 study which compared iriontecan plus cisplatin (IP) with etoposide plus cisplatin (EP) in extensive disease small cell lung cancer patients showed a superior response rate and survival in IP group. We evaluated the efficacy and toxicity of coucnrrent iriontecan plus cisplatin (IP) chemotherapy with thoracic radiotherapy in limited-disease SCLC (LD-SCLC). Methods: From January 2006 to October 2009, thirty chemotherapy-naíve patients with LD-SCLC planned IP induction chemotherapy followed by IP concurrent chemoradiotherapy (CCRT). Twenty-nine patients (97%) were male, and 29 (97%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median age was 60 years. Treatment consisted of one to six cycles of 21-day cycles of irinotecan 65mg/m2 and cisplatin 30mg/m2 intravenously (IV) on days 1 and 8 followed by two 21-day cycles of iriontecan 60mg/m2 IV and cisplatin 30mg/m2, with concurrent thoracic radiotherapy. Results: The objective response was observed in 30 (100%, partial response [PR], 30) of 30 patients after induction chemotherapy and also 28 (100%, complete response [CR], 5; PR, 23) of 28 patients who got concurrent chemoradiotherapy after IP CCRT. After median follow up of 24.2 months, the estimated median survival was 34.2 months (95% CI, 21.2 - 47.2) with 1- and 2-year overall survival rates of 89.1% and 60.9%, respectively. Median progression-free survival (PFS) was 11.6 months with a 1- and 2-year PFS of 46.5% and 22.6%, respectively. The most common toxicities was grade 3 or 4 neutropenia noted in 30% of patients during induction chemotherapy and 15% during CCRT. Febrile neutropenia occurred in 7 % of patients during induction chemotherapy and 7% during CCRT. There was neither grade 3 or 4 esophagitis and radiation pneumonitis nor grade 2 alopecia. Conclusions: IP induction chemotherapy followed by CCRT using IP in LD- SCLC showed a promising activity with favorable 1- and 2-year survival rates, and favorable toxicity in this study. Further studies is warranted for using IP during CCRT. No significant financial relationships to disclose.
Abstract 1262: Primate-specific estrogen-induced long noncoding RNAs as targets for breast cancer treatment
Authors: Donghong Ju, Daniel Xie, Juan Cai, Anton Scott Goustin, Mary A. Kosir, Leonard Lipovich
Journal: Cancer Research (2016)

Abstract Purpose: Estrogen is a proliferative hormone that regulates the growth of estrogen receptor positive cells, including breast cancer cells. Although estrogen is a global regulator of protein-coding genes as well as non-coding RNA (ncRNA) genes, its effects on long ncRNA (lncRNA) genes, the most abundant class of human ncRNAs, remain poorly understood. We previously used custom microarrays and Taqman qRTPCR to identify 127 estrogen-responsive lncRNAs, and demonstrated a direct role for 25 of these in breast cancer cell viability and proliferation: estrogen-induced lncRNAs cause cell proliferation (reversed upon siRNA knockdown of these lncRNAs) and estrogen-repressed lncRNAs cause cell death (induced upon overexpression of those lncRNAs). Furthermore, since over 60% of human lncRNAs, including CR593775, are primate-specific, eight additional primate-specific lncRNAs were used in functional assays to determine whether primate-specific lncRNAs are functional in breast cancer. Methods/Results: We ablated two new estrogen-induced primate-specific lncRNAs with two independent siRNAs each and validated the knockdowns by qRTPCR. Post-transfection MTT and crystal violet cell proliferation assays revealed that for one lncRNA, both knockdowns reduced cell viability and proliferation. We also used Stellaris RNA fluorescent in situ hybridization (FISH) to determine that the primate-specific estrogen-repressed cell death inducer lncRNA BC041455 is cytoplasmic in MCF7 cells. In addition, CR593775, our top estrogen-induced lncRNA, does not regulate the viability and proliferation of nonmalignant MCF10A breast cells as compared to breast cancer cells that are estrogen receptor positive (T47D, MCF7) and negative (MDA-MB-231). Conclusion: The primate-specific estrogen-induced lncRNAs are cytoplasmic targets for breast cancer treatment that leads to reduced proliferation and cell viability. Citation Format: Donghong Ju, Daniel Xie, Juan Cai, Anton Scott Goustin, Mary A. Kosir, Leonard Lipovich. Primate-specific estrogen-induced long noncoding RNAs as targets for breast cancer treatment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1262.