tbuckley/cabot-search huggingface dataset:
Abstract 3874: Mutational landscapes of oral tongue squamous cell carcinoma reveal recurrent mutations in genes of therapeutic and prognostic relevance
Authors: Andre L. Vettore, Kalpana Ramnarayanan, Choon Kiat Ong, Hui Sun Leong, Weng Khong Lim, Ioana Cutcutache, John R. Mcpherson, Shenli Zhang, Thankshayeni Skanthakumar, Daniel SW Tan, Bin Tean Teh, Steve Rozen, Patrick Tan, N Gopalakrishna Iyer
Journal: Cancer Research (2015)

Abstract Carcinoma of the oral tongue (OTSCC) is the most common malignancy of the oral cavity, characterized by frequent recurrence and poor survival. The last three decades has witnessed a change in the OTSCC epidemiological profile, with increasing incidence in younger patients, females and never-smokers. This study aims to characterize the OTSCC genomic landscape and to determine factors that may delineate the genetic basis of this disease, inform prognosis and identify targets for therapeutic intervention. Seventy-eight Asian OTSCC cases were subjected to whole-exome and targeted deep sequencing. While the most common mutation seen was in TP53, the OTSCC genetic landscape differed from previously described cohorts of patients with head and neck squamous cell cancers: OTSCCs demonstrated frequent mutations in DST, FSIP2 and RNF213 while alterations in CDKN2A and NOTCH1 were significantly less frequent than previously reported. Despite a lack of previously-known NOTCH1 mutations, integrated analysis showed enrichments of alterations affecting Notch signaling, more commonly seen in women. Importantly, Notch pathway alterations were prognostic on uni- and multivariate analyses. Furthermore, a high proportion of OTSCCs presented with alterations in drug targetable genes and chromatin remodeling genes. Mutations in these groups were also prognostic, where patients harboring mutations in these actionable pathways more likely to succumb from recurrent disease compared to those who did not, suggesting that these patients should indeed be considered for treatment with targeted compounds in future trial designs. In conclusion, these findings define the mutational landscape of OTSCC, highlight the key role of the Notch signaling pathway in oral tongue tumorigenesis and uncover somatic mutations in therapeutically relevant genes which may represent candidate drug targets. Citation Format: Andre L. Vettore, Kalpana Ramnarayanan, Choon Kiat Ong, Hui Sun Leong, Weng Khong Lim, Ioana Cutcutache, John R. Mcpherson, Shenli Zhang, Thankshayeni Skanthakumar, Daniel SW Tan, Bin Tean Teh, Steve Rozen, Patrick Tan, N Gopalakrishna Iyer. Mutational landscapes of oral tongue squamous cell carcinoma reveal recurrent mutations in genes of therapeutic and prognostic relevance. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3874. doi:10.1158/1538-7445.AM2015-3874
Von Willebrand Factor for Menorrhagia: A Survey and Literature Review
Authors: Nicoletta Machin, Margaret V. Ragni, Lynn M. Malec, Donald Brambilla, Thomas Coyle, Joanna A. Davis, Annette Drygalski, Andra H James, Shawn M Jobe, Barbara A. Konkle, Peter Kouides, Philip Kuriakose, Alice D. Ma, Elaine M. Majerus, Danielle Nance, Anne T. Neff, Claire S. Philipp, Tzu-Fei Wang, Hassan M. Yaish
Journal: Blood (2015)
Costs of haematological disease high and rising
Authors: Tony Green, Dominique Bron, Christine Chomienne, Thom Duyvené de Wit, Fleur de Haas, Andreas Engert, Anton Hagenbeek, Ulrich Jäger, Elizabeth MacIntyre, Martina U Muckenthaler, Carin Smand, Pieter Sonneveld
Journal: The Lancet Haematology (2016)
Prevalence of intestinal metaplasia in the distal esophagus in patients endoscopically suspected for short Barrett's esophagus.
Authors: Antonio Grassi, D. Giannarelli, F. Iacopini, P. Paoluzi, A. Iannetti, L. Giovannelli, C. Efrati, F. Barberani, M. Giovannone, M. Tosoni
Journal: Journal of experimental & clinical cancer research (2006)

The clinical importance of Barrett's esophagus is related to its correlation to adenocarcinoma. The diagnosis is based on histologic demonstration of specialized intestinal metaplasia in the distal esophagus. The aim of this study was to assess the prevalence of intestinal metaplasia of the distal esophagus in a population submitted to gastroscopy not selected for reflux disease, and with columnar lined distal esophagus between 0.5 and 2 cm. Four biopsies in the distal esophagus were done in 224 patients undergoing routine gastroscopy. Patients were not selected for gastroesophageal reflux. Other clinical parameters were recorded to assess any possible association. In four Centers 224 patients received endoscopy with biopsies demonstrating specialized intestinal metaplasia in 21% of cases. No association was present among the patients with esophagitis or hiatal hernia, as well as with reflux symptoms. A significant association was present in over 70 (females), as well as with the presence of antral intestinal metaplasia demonstrated in 45 patients by gastric biopsies. No other significant associations were present. Biopsy samplings can diagnose the presence of intestinal metaplasia during endoscopy in patients endoscopically suspected for Barrett's esophagus: at present there is not clear evidence to promote this screening to achieve mortality reduction of esophageal adenocarcinoma.
Case 46-1962
Authors: John B. Stanbury, Benjamin Castleman
Journal: New England Journal of Medicine (1962)

Presentation of Case First admission. A sixty-three-year-old man was referred to the hospital because of dyspnea.Three weeks previously the patient experienced the onset of increasing shortness of breath, orthopnea and generalized weakness. A physical examination revealed rales at both lung bases and ankle edema. With digitalis therapy the symptoms improved only slightly, and he was admitted to another hospital, where the physical examination revealed a blood pressure of 130 systolic, 98 diastolic, enlargement of the heart and liver, persistent rales in the lungs and ankle edema. X-ray films of the chest (Fig. 1) after a thoracentesis showed cardiomegaly . . .
P0873 : Ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin (RBV) has minimal impact on health-related quality of life (HRQOL) compared with placebo during 12-week treatment in treatment-naïve adults with chronic Hepatitis C (CHC)
Authors: Y. Liu, L. Larsen, S. Zeuzem, E. Coakley, R. Baran, T. Juday
Journal: Journal of Hepatology (2015)
Abstract 2939: Heregulin-induced resistance against HER2-targeted therapies in HER2 positive breast and gastric cancer in vitro and in vivo
Authors: Yoshikane Nonagase, Kimio Yonesaka, Satomi Watanabe, Koji Haratani, Takayuki Takahama, Naoki Takegawa, Hiroto Ueda, Hisato Kawakami, Hidetoshi Hayashi, Masayuki Takeda, Haruka Sakamoto, Takao Tamura, Kazuhiko Nakagawa, Junji Tsurutani
Journal: Cancer Research (2016)

Abstract Background HER2-targeted therapies have been shown clinical benefits in patients with HER2 positive breast and gastric cancers. However, resistance against such targeted therapies eventually develops in most cases. Overexpression of heregulin, a ligand for HER3, has been reported as one of the resistant mechanism against HER2-targeted therapies. Upregulation of heregulin activates HER3-PI3K-AKT signaling, leading to the resistance against HER2-targeted therapies. We investigated the effects of heregulin in cell lines and evaluate its clinical impacts in HER2 positive breast and gastric cancers. Materials and methods We utilized transfected or recombinant heregulin to investigate the effect of heregulin on proliferation and apoptosis of SK-BR-3 and NCI-N87 cell lines treated with lapatinib, trastuzumab, trastuzumab-emtansine and paclitaxel. Clinical data and specimens were obtained from patients with HER2 positive breast and gastric cancers, evaluating their heregulin value from both serum and tissues using ELISA and RT-PCR, respectively. Results Heregulin transfection and recombinant heregulin conferred resistance against treatment with lapatinib, trastuzumab, and weak resistance against trastuzumab-emtansine, but no resistance against paclitaxel in HER2 positive cell lines. Clinical data of heregulin among patients treated with HER2-targeted therapies revealed that patients with relatively high heregulin value tended to have worse prognosis. Conclusions Together these data, overexpression of heregulin may at least in part play a role in resistance against HER2-targeted therapies in HER2 positive cancer patients. Further investigation is warranted to elucidate the relevance of treatments targeting heregulin-HER3-PI3K signaling. Citation Format: Yoshikane Nonagase, Kimio Yonesaka, Satomi Watanabe, Koji Haratani, Takayuki Takahama, Naoki Takegawa, Hiroto Ueda, Hisato Kawakami, Hidetoshi Hayashi, Masayuki Takeda, Haruka Sakamoto, Takao Tamura, Kazuhiko Nakagawa, Junji Tsurutani. Heregulin-induced resistance against HER2-targeted therapies in HER2 positive breast and gastric cancer in vitro and in vivo. [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 2939.
Routine Cancer Antigen 125 Surveillance—The Fatal Attraction of Testing
Authors: James S. Goodwin
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Hospitalizations and deaths within 60 days of fluoropyrimidine chemotherapy initiation among Medicare patients with colorectal cancer.
Authors: Gabriel Brooks, Angel Cronin, Deborah Schrag
Journal: Journal of Clinical Oncology (2016)

3603 Background: Fluoropyrimidine (FP) drugs are the basis of chemotherapy for colorectal cancer (CRC). FP chemotherapy carries risk for severe toxicity and death, however the incidence of these complications among elderly patients is poorly described. Methods: We used the SEER-Medicare data to identify adults age ≥ 65 who received FP chemotherapy (5-FU or capecitabine) for CRC. All subjects were diagnosed with CRC in 2003-11. Intent of chemotherapy was classified as adjuvant for patients diagnosed with locoregional colon cancer who had colectomy and initiated chemotherapy within 180 days of diagnosis. Therapy intent was classified as palliative for patients with metastatic CRC and for patients who initiated chemotherapy for CRC >180 days after diagnosis. Patients with rectal cancer were excluded from the adjuvant therapy group due to overlapping toxicities of FP drugs and radiation. We then identified first hospitalizations and deaths occurring within 60 days of FP initiation. Hospitalizations were considered FP-associated when a diagnosis code for neutropenia, thrombocytopenia, diarrhea, gastroenteritis, stomatitis, or mucositis was present on the hospital claim. Deaths were considered FP-associated when death followed FP-associated hospitalization and occurred within 60 days of FP initiation. Results:See table. Conclusions: 8% of Medicare patients receiving FP chemotherapy for CRC were hospitalized with symptoms of FP toxicity within 60 days of chemotherapy initiation. Further research is warranted to investigate the contribution of evaluable risk factors (including polymorphisms of the DPYD gene) to FP-associated hospitalizations and deaths. Events within 60 days of FP initiation Colon cancer, adjuvant Rx (95% CI) Colorectal cancer, palliative Rx (95% CI) Subjects (n) 13,268 11,134 Hospitalization, any (%) 18.9 (18.3-19.6) 24.9 (24.1-25.7) - Hospitalization with FP toxicity (%) 8.7 (8.2-9.2) 8.0 (7.5-8.50) Death, any cause (%) 1.9 (1.7-2.2) 7.1 (6.6-7.6) - Death after FP-associated hospitalization (%) 0.7 (0.6-0.9) 1.4 (1.2-1.7)
Abstract LB-137: IGF2BP1 and miR-34a genetic instability found in deadly neuroblastoma
Authors: Jessica L. Bell, Stefan Hüttelmaier
Journal: Cancer Research (2016)

Abstract Chromosomal 17q21-ter gain in neuroblastoma is both a common and clinically significant occurrence. The oncogenic, insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) gene is located near the proximal edge of this region. We have previously reported that in 69 neuroblastoma samples, IGF2BP1 DNA copy number (increased in 84% of tumors), mRNA, and protein levels are significantly higher in stage 4 compared with stage 1 tumors. Moreover, clinical and experimental data pointed to a strong association of IGF2BP1 with the MYCN oncogene. From the late 1990s onwards, 17q gain and 1p deletions (either alone or both) have been speculated as essential precursors to the MYCN amplification. As the tumor suppressive, miR-34a is located within 1p and is known to directly target MYCN and putatively IGF2BP1 mRNAs (Targetminer website), in this study we analyzed the co-occurrence of IGF2BP1 gain, miR-34a loss and MYCN amplification) in 69 neuroblastomas. qPCR was utilized to assess copy number. Changes were found for IGF2BP1 (58 tumors), miR-34a (15) and MYCN (12). miR-34a was never completed deleted. Interestingly, in all (12/12) MYCN amplified tumors, miR-34a was partially lost. Whilst, IGF2BP1 was gained in 9/12 MYCN amplified tumors. IGF2BP1 and miR-34a were aberrant together only twice with the absence of MYCN amplification. Of the 17 patients that died, all but one had at least an IGF2BP1 or miR-34a change in copy number. This stage 4 patent also had low MYCN protein levels, comparable to the stage 1 patients, indicating an aggressive tumor not involving the MYCN pathway. may A second larger cohort is certainly required to confirm these important results. IGF2BP1 and miR-34a locus have aberrant copy numbers in the majority of neuroblastoma, most strikingly, in the patients that died. IGF2BP1 and miR-34a may just be representative DNA of the larger locus changes and not be the causative event in affected neuroblastoma, but because of their known roles in cancer, the above results are intriguing. Although further experimental data is required, we speculate that either IGF2BP1 or mir-34a oncogenic changes are required for the clonal expansion of MYCN amplified tumor cells in neuroblastoma, and that these factors are crucial in the ability for an increase in MYCN transcription to be oncogenic in neuroblastoma. Citation Format: Jessica L. Bell, Stefan Hüttelmaier. IGF2BP1 and miR-34a genetic instability found in deadly neuroblastoma. [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 LB-137.
Activity of recombinant human interleukin-21 (rIL-21) in patients (pts) with stage IV malignant melanoma (MM) without prior treatment: Clinical data from a phase IIa study
Authors: I. D. Davis, B. Brady, R. Kefford, M. J. Millward, B. K. Skrumsager, U. Mouritzen, P. E. Kristjansen, G. A. McArthur
Journal: Journal of Clinical Oncology (2008)

3042 Background: IL-21 has a key role in cancer immunology. We have previously described a phase 1 study of rIL-21 in pts with advanced MM. We now report final clinical results from a phase 2a study in treatment-naïve pts with advanced MM. Methods: Open-label, two-stage phase 2a trial. Primary objective: antitumor efficacy as determined by response rate. Secondary objectives: safety, effects on blood biomarkers, measurement of anti-rIL-21 antibodies. Eligibility: unresectable MM, measurable disease by RECIST, no prior systemic therapy (adjuvant interferon permitted), adequate major organ function, good performance status, no significant autoimmune disease, life expectancy ≥4 months. rIL-21 was administered at 30 μg/kg/dose in cycles of 5 dosing days followed by 9 days of rest for 6 weeks (wks), followed by 2 wks off treatment. Further cycles were offered to pts without tumor progression causing symptoms and requiring other therapy. Only pts with PR or CR by RECIST at wk 16 were offered further treatment. Results: Stage 1 of the study comprised 14 pts. One confirmed CR was observed and as per protocol 10 more pts were accrued to stage 2 (total n=24: 10 female, 14 male). Best tumor response any time on study included 1 confirmed CR and 1 confirmed PR (both with lung mets) with overall RR 8.3%, 8 SD (33.3%) and 14 PD (58.3%). The pt with CR by wk 8 had PD 11 wks later. The pt with PR had SD at wk 8 but confirmed PR at wk 16. 6/8 pts with SD at wk 8 had progressed by wk 16. Another pt had CR in target lesions and SD in non-target, but PD in brain (overall PD). One pt had 9 cycles of treatment, 10 had 6, and 13 had 3–4. Treatment was well tolerated and safety was similar to the phase 1 trial. 8 pts had SAEs: hypersensitivity (1), hepatitis (1), fever (2), rigor (1), cellulitis (1), sinus tachycardia (1), cancer related pain (4). One pt withdrew due to adverse events at wk 8 and 3 pts had the dose reduced to 10 μg/kg. Conclusions: rIL-21 administered at 30 μg/kg/day in 5-day cycles every 2nd wk was well tolerated by pts with metastatic MM and confirmed responses by RECIST including one CR were observed. Future studies will evaluate potential for further anti-tumor activity at higher doses of rIL-21. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novo Nordisk A/S Novo Nordisk A/S Novo Nordisk A/S
The effect of low-dose GTx-758 on free testerone levels in men with metastatic castration resistant prostate cancer (mCRPC).
Authors: Evan Y. Yu, Robert H. Getzenberg, Jordan Smith, Michael L. Hancock, Ronald Tutrone, Thomas W. Flaig, James T. Dalton, Mitchell S. Steiner, Karl R Westenfelder, Miklos Szucs
Journal: Journal of Clinical Oncology (2014)

60 Background: Luteinizing hormone-releasing hormone (LHRH) agents used for androgen deprivation therapy (ADT) were designed to lower total testosterone (T) levels to those achieved by orchiectomy for palliative care of advanced prostate cancer. This castration equivalent level was based upon the lower limits of quantitation (50ng/dL) of outdated assays. Contemporary assays reveal that actual total T levels in men after orchiectomy are significantly lower (&lt;20ng/dL), with 30 to 40% of men on LHRH agonists not achieving that level. There is growing literature showing that lower T levels correlate with improved outcomes. Additionally, the biologically active form of T is unbound, free T. GTx-758 (Capesaris) is an oral estrogen receptor α agonist that increases sex hormone binding globulin (SHBG), lowers free T levels, and ameliorates estrogen deficiency side effects associated with ADT. Methods: In a phase II open label study (G200712), 38 men with metastatic castration resistant prostate cancer (mCRPC) were continued on their current form of ADT along with a low dose of GTx-758, 125 mg, for at least 90 days. Exclusion criteria included men at increased risk for venous thrombolic events (VTE). Results: The initial 14 patients in this trial completed 90 days on study and are evaluable for select trial endpoints. All treated men had a greater than or equal to a 150% increase in SHBG levels. Eleven of the 14 men began the study with suboptimal castration (free T &gt;0.7 pg/ml) and 91% (10 out of 11) of these men became optimally castrated by day 90. Four out of 14 patients had a more than 45% decrease in prostate-specific antigen. Stable or improved hot flashes and bone turnover markers were observed in 71% and 73% of treated men, respectively. While some patients experienced adverse events, none were vascular related and there were no serious adverse events or VTEs. Conclusions: The majority of patients on an LHRH agonist enrolled in this phase II study had suboptimal levels of free T that were further lowered by GTx-758 administration. GTx-758 treatment resulted in stabilization and/or improvement in reported hot flashes and bone turnover, two major side effects of ADT. While the phase II clinical trial is ongoing, and full results are forthcoming, these preliminary findings show that 125 mg of GTx-758 has clinical effectiveness and is well tolerated. Exploration of 250 mg a day is planned. Clinical trial information: NCT01615120.
Somatic Mutations Detected in Plasma Cell-Free DNA By Targeted Sequencing: Assessment of Liquid Biopsy in Primary Central Nervous System Lymphoma
Authors: Maxime Fontanilles, Florent Marguet, Élodie Bohers, Pierre-Julien Viailly, Philippe Bertrand, Sydney Dubois, Sylvain Mareschal, Vincent Camus, Elena-Liana Veresezan, Philippe Ruminy, Hervé Tilly, Annie Laquerriere, Jean-Michel Picquenot, Fabrice Jardin
Journal: Blood (2015)
Abstract 3030: CT179: A novel small molecule Olig2 inhibitor for the treatment of glioblastoma
Authors: Gordon Alton, Graham Beaton, Susan Knowles, Greg Stein, Rajesh Mukthavaam, Santosh Kesari
Journal: Cancer Research (2016)

Abstract Glioblastoma (GBM) is an orphan disease with a high unmet medical need. Despite optimal treatment, the median survival is only 12 to 15 months in GBM patients of which only 4% achieve 5-year survival. OLIG2 is a transcription factor that is almost exclusively expressed in the CNS that has been linked to the tumorigenesis of GBM cells and their resistance to radiotherapy. Importantly OLIG2 is a key transcription factor that maintains the stemness of the glial stem cells, drives proliferation and invasion and recurrent tumor growth. Inhibitors of this pathway are therefore of interest as potential treatments for this unmet need. CT-179 is a small molecule inhibitor that was initially designed to prevent homodimerization of Olig2. CT-179 is highly cytotoxic to OLIG2 expressing GBM cells with a high therapeutic index for non-OLIG2 expressing cell types. This inhibitor demonstrates functional inhibition of the OLIG2 pathway through specific reduction in nuclear Olig2 protein levels in treated cells. A cell pathway analysis indicates that CT-179 impacts GBM proliferation through cell cycle arrest and induction of apoptosis. Secondarily an immunosuppression mechanism-of-action may also be relevant. CT-179 penetrates the CNS to attain high brain concentrations at levels far in excess of its cytotoxicity to GBM cells. Efficacy studies reveal dose dependent reductions of tumor growth which is enhanced with radiotherapy. CT-179 demonstrates impressive extension of survival in orthotopic human PDX GBM. Safety studies indicate that there is a large therapeutic window. The compound has a long half-life, low metabolism and has excellent formulation properties and PK supporting once per day oral dosing. CT-179 show promise as both a cytotoxic agent and as potential radiosensitizer for use in the treatment of GBM. Citation Format: Gordon Alton, Graham Beaton, Susan Knowles, Greg Stein, Rajesh Mukthavaam, Santosh Kesari. CT179: A novel small molecule Olig2 inhibitor for the treatment of glioblastoma. [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 3030.