tbuckley/cabot-search huggingface dataset:
Phase I study of 5-FU and arsenic trioxide (ATO) in patients with refractory metastatic colorectal carcinoma.
Authors: B. Ardalan, P. R. Subbarayan, Y. Ramos, M. Gonzalez, D. Mezentsev, I. M. Reis, R. Duncan, P. Ganjei-Azar, K. Lee
Journal: Journal of Clinical Oncology (2010)

e14081 Background: In vitro, prolonged exposure of colon cancer cells to 5-FU induces resistance and is associated with increased synthesis of thymidylate synthase (TS). 5-FU resistance is well correlated with the over expression of intratumoral TS mRNA which if down regulated may reverse 5FU resistance. Earlier we demonstrated that ATO significantly down regulated TS in vitro and in patients thereby sensitizing them back to 5-FU. Methods: A treatment cycle consisted of four weeks of therapy and one week of rest. On days one through five, 8, 11, 15 and 22, the patients (pts.) received a 4-hour ATO infusion; on days 8, 15 and 22 a 24-hour 5 FU/ leucovorin infusion. To date 12 pts with refractory metastatic colorectal carcinoma were enrolled. In the 5-FU dose escalation phase, patient one received 1,600 mg/ m2; patient two 2,000 mg/m2; patient three 2,300 mg/m2; patient four and all the subsequent patients 2,600 mg/m2 of 5-FU. ATO was infused at 0.15 mg/kg in patient one through seven and at 0.20 mg/kg in patient eight through 12. Peripheral blood mononuclear cells (PBMC) were obtained before and during therapy. Pre treatment and end of cycle 1 tumor specimen were obtained. TS levels were monitored by RT-PCR. Results: The toxicities were as follows: No patient experienced grade 4 toxicities. Grade 3 toxicity: diarrhea (2 pts.), neutropenia (1); QTc prolongation (1), fatigue (2), alkaline phosphatase (1). Grade 2 toxicity: anorexia (1), constipation (1), fatigue (2), edema (1), nausea and vomiting (1). Two patients developed herpes zoster (Gr. 3) outbreak which resolved with acyclovir. Plasma As2O3 levels ranged from 41 to 157 μg/L. ATO suppresses TS transcription: We measured TS mRNA levels in eight pairs of tumor tissues and PBMC of all patients. In four out of 8 patients, the end of cycle 1 TS level was reduced by over 70% in tumor samples. In three tissue specimen the post treatment TS level increased and in one remained unchanged. TS was down regulated in all the PBMC samples analyzed (proof of hypothesis). Conclusions: 1) 0.2 mg/kg of ATO and 2,600 mg/m2 of 5-FU regimen have manageable toxicity and determined to be the MTD. Supported by NCI grant 1R21CA117116- 01A2. No significant financial relationships to disclose.
Antitumor activity of MDV3100 in pre- and post-docetaxel advanced prostate cancer: Long-term follow-up of a phase I/II study.
Authors: C. S. Higano, T. M. Beer, M. Taplin, E. Efstathiou, A. Anand, M. Hirmand, M. Fleisher, H. I. Scher
Journal: Journal of Clinical Oncology (2011)

134 Background: MDV3100 is a novel androgen receptor (AR) antagonist selected for potent AR activity and devoid of partial agonist effects. A preliminary report of the phase I/II study described anti-tumor activity and adverse events (Scher HI et al. Lancet. 2010;375:1437). This abstract provides long-term follow-up on time to PSA and radiographic progression in this trial. Methods: Patients (pts) with progressive castration resistant prostate cancer (CRPC) were enrolled in sequential cohorts of 3-6 pts at MDV3100 doses of 30, 60, 150, 240, 360, 480 and 600 mg/day. Once the tolerability of a dose was established, enrollment was expanded at doses ≥60 mg/day to include approximately 12 chemotherapy naïve (naïve) pts and 12 pts previously treated with docetaxel (post-chemo) per cohort. Results: 140 pts were enrolled of which 18 (13%) pts continue on active treatment (16 naive and 2 post-chemo). The median time on treatment is 51 weeks for naïve and 17 weeks for post-chemo groups. Median time on treatment for the 18 patients still on study is 131 weeks. The median time to PSA progression, defined per-protocol as a ≥25% increase in PSA from baseline, was not met for naïve and was 33 weeks for post-chemo groups. Median time to PSA progression by Prostate Cancer Clinical Trials Working Group 2 criteria was 41 weeks for naïve and 20 weeks for post-chemo groups. Median time to radiographic progression was 56 weeks for naive and 24 weeks for post-chemo groups. Circulating tumor cell counts available for 128 of 140 pts showed 91% (70/77) with favorable pre-treatment counts (&lt;5 cells/7.5 mL blood) remaining favorable post-treatment, while 49% (25/51) converted from unfavorable pre-treatment to favorable post-treatment. Conclusions: MDV3100 demonstrates durable anti-tumor activity in pts with CRPC both before and after chemotherapy. Based on these promising results MDV3100 is currently being evaluated in two global phase III studies in pts with metastatic CRPC, the AFFIRM study in pts previously treated with docetaxel and the PREVAIL study in chemotherapy-naïve pts who have progressed on androgen deprivation therapy. [Table: see text]
Genomic profiling of small bowel adenocarcinoma: Insights from a comparative analysis with gastric and colorectal cancer and opportunities for targeted therapy
Authors: A.B. Schrock, C.E. Devoe, R. McWilliams, J. Sun, J.T. Ruggiero, P. Stephens, J.S. Ross, R. Wilson, V.A. Miller, S.M. Ali, M.J. Overman
Journal: Annals of Oncology (2016)
Neutrophil PRV-1 mRNA Overexpression in Chronic Idiopathic Myelofibrosis May Be Associated with Poor Prognosis.
Authors: Heinz Gisslinger, Steffen Klippel, Hermann Heimpel, Mathias Kees, Alexandra Kaider, Juergen Thiele, Heike L. Pahl
Journal: Blood (2004)
Prognostic impact of comorbidity in stage II-III colorectal cancer (CRC) patients treated with surgery and neoadjuvant/adjuvant chemotherapy: a single Institution observational study
Authors: M. Baretti, L. Giordano, L. Rimassa, M.C. Tronconi, T. Pressiani, S. Bozzarelli, N. Personeni, A. Santoro
Journal: Annals of Oncology (2016)
ANGI-03. STANNIOCALCIN-1 EXPRESSION IN GLIOBLASTOMA IS ASSOCIATED WITH LEPTOMENINGEAL DISSEMINATION OR METASTASIS
Authors: Junichi Sakata, Takashi Sasayama, Kazuhiro Tanaka, Mitsutoshi Nakada, Naoya Hashimoto, Manabu Kinoshita, Naoki Kagawa, Katsu Mizukawa, Hiroaki Nagashima, Naoko Sato, Eiji Kohmura
Journal: Neuro-Oncology (2016)

Dissemination or metastasis (D/M) occasionally occurs in glioblastomas (GBMs), and those cases have very poor prognosis. MicroRNAs (miRs) have been shown to involve metastasis in various tumors. The aim of this study is to clarify the miRs which promote D/M and to find a target molecule associated with them in GBMs. Twenty-two supratentorial GBMs with D/M to spinal cord or medulla oblongata (GBMswith) and 53 GBMs without D/M (GBMswithout) were analyzed. The expression levels of 22 miRs which were known to be related to GBM were examined, and miRs which were statistically upregulated or downregulated in GBMwith compared to GBMwithout were determined. Then, we searched the targets of these miRs by the web site of “microRNA.org”, and analyzed the association of miRs with target molecule by real-time PCR and Western blot. Furthermore, we analyzed the functions and the expressions of the target molecule in GBMs. Eight miRs (miR-7, miR-29b, miR-34a, miR-101, miR-124, miR-128a, miR-137, miR-218) were statistically decreased in GBMwith compared to GBMwithout, and mimic RNAs of these miRs inhibited cell proliferation and migration in glioma cells. As the most predictive target of these miRs, we focused on stanniocalcin-1 (STC1). STC1 is a secreted, homodimeric glycoprotein and involved in metastasis in various cancers. We confirmed that the mimic RNAs of these miRs (miR-29b, miR-34a, miR-101) decreased the expression of STC1. Knockdown of STC1 inhibited the cell proliferation and migration. STC1 protein was higher expressed in GBMs than that in low grade gliomas. Futhermore, GBMwith had statistically higher expression levels of STC1 than GBMwithout had. Several studies have reported that the high level expression of STC1 was associated with ischemia and metastatic cancer. STC1 may be the target of miRs downregulated in GBMwith, and may be one of the key molecules of metastasis or dissemination in GBMs.
Development and validation of a patient-reported outcome instrument for skin involvement in patients with systemic sclerosis
Authors: Ada Man, Jeannette K Correa, Jessica Ziemek, Robert W Simms, David T Felson, Robert Lafyatis
Journal: Annals of the Rheumatic Diseases (2017)

We developed a patient-reported outcome (PRO) instrument to assess the skin-related quality of life in patients with systemic sclerosis (SSc).Participants with SSc provided input on skin-related health effects through focus groups. We developed items for scleroderma skin PRO (SSPRO) to encompass these effects. Further consideration from cognitive interviews and an expert panel led to reduction and modification of items. A 22-item SSPRO was field tested. Psychometric analysis included test-retest reliability, internal consistency and exploratory factor analysis (EFA). Construct validity was assessed through correlation with other participant and physician-assessed measures.140 participants completed the SSPRO: mean age was 53.4 years, median disease duration was 5 years, 82.1% were female and 32.9% had diffuse cutaneous SSc. EFA supported four factors in SSPRO corresponding to hypothesised constructs: physical effects, physical limitations, emotional effects and social effects. Removal of 4/22 items resulted in acceptable goodness-of-fit statistics. Test-retest reliability (intraclass correlation coefficient=0.61-0.83) was moderate to high and internal consistency (Cronbach's α=0.89-0.96) was high. SSPRO correlated strongly with other participant-reported measures (r=0.59-0.88) suggesting construct validity, and less well with physician-assessed measures (r=0.31-0.40). SSPRO scores were significantly different for each level of participant-reported skin severity, and for limited versus diffuse cutaneous SSc.SSPRO has been developed with extensive patient input and demonstrates evidence for reliability and validity. It is complementary to existing measures of SSc skin involvement with emphasis on the patient's experience. Further research is needed to assess its sensitivity to change.
A New Prognostic Score for Patients Older Than 60 Years with a Classical Hodgkin Lymphoma: A Retrospective Analysis on 165 Patients
Authors: Violaine Safar, Nadia Oussaid, Alexandra Traverse-Glehen, Catherine Chassagne-Clement, Catherine Sebban, Anne-Sophie Michallet, Pierre Biron, Emmanuel Bachy, Emmanuelle Nicolas-Virelizier, Francoise Berger, Bertrand Coiffier, Gilles Salles, Herve Ghesquieres
Journal: Blood (2014)
Non-drug therapies should be first line treatment for low back pain, US guidance says
Authors: Michael McCarthy
Journal: BMJ (2017)

New guidelines from the American College of Physicians recommend that physicians avoid prescribing drugs, particularly opioids, to treat acute and subacute low back pain and should instead emphasize non-pharmacologic therapies, such as superficial heat, massage, and physical therapy.

“Clinicians should reassure patients that acute or subacute low back pain usually improves over time, regardless of treatment. Thus, clinicians should avoid prescribing costly and potentially harmful treatments for these patients, especially narcotics,” the guidelines said.

If clinicians decide to use a pharmacologic agent, non-steroidal anti-inflammatory drugs or skeletal muscle relaxants should be used, …
Outcomes of elderly chemorefractory metastatic colorectal (mCRC) patients (pts) treated with regorafenib: a single institution experience
Authors: C. Cardone, V. Sforza, A. Nappi, A. Capasso, M.L. Ferrara, G. Martini, S. Napolitano, P. Vitiello, P. Vitale, N. Zanaletti, M. Diadema, M. Orditura, F. De Vita, T. Troiani, F. Ciardiello, E. Martinelli
Journal: Annals of Oncology (2016)
Interim analysis of a phase I dose escalation trial of ASG-22CE (ASG-22ME; enfortumab vedotin), an antibody drug conjugate (ADC), in patients (Pts) with metastatic urothelial cancer (mUC)
Authors: J.E. Rosenberg, E. Heath, R. Perez, J. Merchan, J. Lang, D. Ruether, D. Petrylak, R. Sangha, D.C. Smith, S. Sridhar, E. Gartner, M. Vincent, R. Chu, B. Anand, F. Donate, A. Melhem-Bertrandt, J. Zhang
Journal: Annals of Oncology (2016)
Description and prognostic value of the mutational load across various metastatic solid tumors in the prospective MOSCATO-01 and MATCH-R trials
Authors: L. Mahjoubi, M. Pedredo, C. Massard, E. Castanon Alvarez, C. Lefebvre, L. Lacroix, Y. Loriot, F. André, J.-C. Soria
Journal: Annals of Oncology (2016)
Toxicity and Early Response after Intravenous (IV) Busulfan (Bu) Plus Melphalan (Mel) Conditioning for Autologous Stem Cell Transplantation (SCT) in Patients (pts) with Multiple Myeloma (MM).
Authors: Partow Kebriaei, Sergio Giralt, Timothy L. Madden, Neil Thapar, Elizabeth J. Shpall, Chitra Hosing, Muzaffar H. Qazilbash, Daniel R. Couriel, Uday Popat, Peter F. Thall, Richard E. Champlin, Roy Jones, Borje S. Andersson
Journal: Blood (2006)
Is the benefit of adjuvant chemotherapy limited to high-risk stage ii colorectal cancer?
Authors: M. Roberto, A. Romiti, E. Pilozzi, G. Balducci, M. Ferri, S. Uccini, R. Falcone, G. Campisi, P. Mercantini, F. Mazzuca, F.R. Di Pietro, C.E. Onesti, A. Botticelli, P. Marchetti
Journal: Annals of Oncology (2016)
Time Point-Dependent Concordance of Flow Cytometry and RQ-PCR in the MRD Detection in Childhood ALL: The Experience of the AIEOP-BFM- ALL MRD Study Group
Authors: Giuseppe Gaipa, Giovanni Cazzaniga, Renate E Panzer-Grümayer, Marinella Veltroni, Leonid Karawajew, Daniela Silvestri, Barbara Buldini, Richard Ratei, Andre Schrauder, Martin Schrappe, Wolf-Dieter Ludwig, Maria Grazia Valsecchi, Andrea Biondi, Michael N Dworzak, Giuseppe Basso
Journal: Blood (2008)
Randomized Phase II Trial of Timed Sequential Cytosine Arabinoside with and without the CHK1 Inhibitor MK-8876 in Adults with Relapsed and Refractory Acute Myelogenous Leukemia
Authors: Jonathan Allen Webster, Raoul Tibes, Amanda Blackford, Lawrence Morris, Mrinal M Patnaik, Lihua Wang, Melanie Rebechi, Jacqueline Greer, Mark R Litzow, Larry Karnitz, Gary L. Rosner, Austin Doyle, Scott H. Kaufmann, Judith E Karp, B. Douglas Smith
Journal: Blood (2015)
Lymphotoxin-β Interacts with Methylated EGFR to Mediate Acquired Resistance to Cetuximab in Head and Neck Cancer
Authors: Dennis Shin-Shian Hsu, Wei-Lun Hwang, Chiou-Hwa Yuh, Chen-Hsi Chu, Yang-Hui Ho, Pon-Bo Chen, Han-Syuan Lin, Hua-Kuo Lin, Shih-Pei Wu, Chih-Yi Lin, Wen-Hao Hsu, Hsin-Yi Lan, Hsiao-Jung Wang, Shyh-Kuan Tai, Mien-Chie Hung, Muh-Hwa Yang
Journal: Clinical Cancer Research (2017)

Purpose: In head and neck squamous cell carcinoma (HNSCC), the incidence of RAS mutation, which is the major cause of cetuximab resistance, is relatively rare compared with the other types of cancers, and the mechanism mediating acquired resistance is unclear compared with the driver gene mutation-mediated de novo resistance. Here, we investigated the driver gene mutation-independent mechanism for cetuximab resistance in HNSCC.Experimental Design: We used the in vitro-selected and in vivo-selected cetuximab-resistant sublines of HNSCC cell lines for investigating the mechanism of acquired resistance to cetuximab. Zebrafish model was applied for evaluating the synergistic effect of combinatory drugs for overcoming cetuximab resistance.Results: The cetuximab-resistant HNSCC cells undergo a Snail-induced epithelial-mesenchymal transition. Mechanistically, Snail induces the expression of lymphotoxin-β (LTβ), a TNF superfamily protein that activates NF-κB, and protein arginine methyltransferase 1 (PRMT1), an arginine methyltransferase that methylates EGFR. LTβ interacts with methylated EGFR to promote its ligand-binding ability and dimerization. Furthermore, LTβ activates the NF-κB pathway through a LTβ receptor-independent mechanism. Combination of an EGFR tyrosine kinase inhibitor and a NF-κB inhibitor effectively suppressed cetuximab-resistant HNSCC and interfering with the EGFR-LTβ interaction reverses resistance.Conclusions: Our findings elucidate the mechanism of driver gene mutations-independent mechanism of acquired resistance to cetuximab in HNSCC and also provide potential strategies for combating cetuximab resistance. Clin Cancer Res; 23(15); 4388-401. ©2017 AACR.
Molecular and Biological Characteristics of Tumour Substrate in Patients with Extramedullary Multiple Myeloma
Authors: Maya V. Firsova, Larisa P. Mendeleeva, Alla M. Kovrigina, Natalia L. Deineko, Maxim V. Solovev, Maria V. Nareyko, Larisa A. Kuzmina, Valery G. Savchenko
Journal: Blood (2016)
Considering Blood Pressure Level in the Association Between Serum Calcium Level and the Size and Expansion in Patients With Intracerebral Hemorrhage—Reply
Authors: Andrea Morotti, Jonathan Rosand, Joshua N. Goldstein
Journal: JAMA Neurology (2017)

In Reply We would like to thank Dr Chen and colleagues for their interest in our study investigating the association between serum calcium level and the extent of bleeding in patients with acute intracerebral hemorrhage (ICH).
A Phase I/II Study Combining Sunitinib with Standard Ara-C/Daunorubicin Chemotherapy In Patients 60 Years or Older with FLT3 Mutated AML
Authors: Walter Fiedler, Jürgen Krauter, Katharina Götze, Helmut R. Salih, Carsten Bokemeyer, Daniela Spaeth, Konstanze Döhner, Hartmut Döhner, Richard F. Schlenk
Journal: Blood (2010)
Bi-weekly oxaliplatin (oxa) and gemcitabine (gem) in cisplatin pretreated patients with relapsed ovarian cancer (roc): Preliminary data of a phase II trial
Authors: D. Germano, D. Bilancia, A. Di Nota, A. M. Dello Russo, R. Romano, G. Rosati, F. Giotta, L. Manzione
Journal: Journal of Clinical Oncology (2004)

5104 Background: Both OXA and GEM have shown single agent activity in pts with ROC. Responce rates to second-line therapies remain low and there is a need to develop more effective regimens. In view of the synergistic effect using the sequence GEM followed by OXA ( Faivre S, Cancer Chemother Pharmacol 1999, 44(2): 117–23), we studied these agents in pts with ROC heavely pretreated. The aim of the study was to evaluate the efficacy and toxicity of combination of GEM 1000 mg/m2 D1 IV and OXA 100 mg/m2 in 2h infusion D2, treatment was repeated every 2 weeks until progression of desease or intollerable toxicity Methods: The study was monoinstitutional and started in November 2002.To date 15 patients, median age 66 years (range 52–82) have been treated. Median Karnofski Performance Status was 70 % (range 60–90), all had at least 1 prior platinum based chemotherapy and 11 had received a taxane Results: At November 2003 of 15 patients entered onto study, 13 were assesable. Pts received a median of 6 cycles of treatment ( range 4–11). There was 1 patient (7.7%) with complete response, 3 patients (23 %) achieved a partial response. Using the technique of Rustin et al. (JCO 1996, 14:5; 1545–1551) Ca 125 responses occurred in 3 of the 4 responding patients. As concerns toxicity, a low profile (grade 1 -2, WHO criteria) was observed: nausea 38.5%, trombocytopenia 30.7%, neuropaty 38.5%. Conclusions: The GEMOX combination is extremely well tolerated and even in this small pts group encouraging responses have been documented. Recruitment continues and further data will be presented. No significant financial relationships to disclose.
Breast cancer in young women less than 30 years from southern India: Study on clinical profile and outcome
Authors: R. Rejiv, D. Biswajit, R. Neelesh, V. Sridevi, T. G. Sagar, V. Shanta
Journal: Journal of Clinical Oncology (2009)

e22196 Background: Breast cancer in young patients have an aggressive behaviour with poorer outcome. The patients are in their reproductive age group and are concerned with fertility issues,pregnancy and lactation. The literature pertaining to patients less than 30 years is limited. Methods: 213 Patients under the age of 30 years with breast cancer were studied for Demographics, clinical presentations, pathological profiles, treatment and survival. The case records were retrospectively analyzed between Jan 1993 - Dec 2003 at Cancer Institute (WIA) Chennai. Results: The mean age of the study population was 28 years and ranged between 17 to 30 years. Early menarche, defined as less than 12 years (17.5 %), Nulliparity (21.1%), first child birth less than 18 years (26.8%) were the major risk factors noted. Family history of breast and ovarian cases were seen in 6.6% of the patients. The Stage distribution included Stage I (1.4%), Stage II (31%), Stage III (49.6) and Stage IV (11%) and unclassifiable (7%). Node positive tumours constituted 158 patients (74.1%). Hormone receptor studies were negative in 62% of the patients. Modified radical mastectomy was performed in 164 (77%) of the patients. Non infiltratring ductal carcinoma histopathology was noted in 13.6%. Surgical and radiocastration was performed in 35.2% and 17% of the cases respectively. Of 201 (94.3%) patients who received chemotherapy anthracycline based chemotherapy was delivered in 30.3%. Recurrence pattern included local, local and distant and distant recuurences in 8.5%, 23.5% and 2.3% respectively. The 5 year over all survival for the evaluable patients was 53.2%. Conclusions: Very young Indian patients less than 30 years constitute a unique subset of breast cancer patients with majority being hormone receptor negative and locally advanced stage at presentation. The over all outcome is inferior compared to older patients with breast cancer. More aggressive adjuvant treatment may help in improving survival. No significant financial relationships to disclose.
TONSILLECTOMY AND POLIOMYELITIS
Journal: JAMA (1962)

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Role of Reduced-Intensity Conditioning Followed by Allogeneic Stem Cell Transplantation In Patients with Multiple Myeloma Relapsing After Autograft: a Donor Versus No Donor Analysis
Authors: Francesca Patriarca, Hermann Einsele, Francesco Spina, Benedetto Bruno, Chiara Nozzoli, Miriam Isola, Alessandra Sperotto, Andrea Nozza, Fortunato Morabito, Gernot Stuhler, Moreno Festuccia, Alberto Bosi, Renato Fanin, Paolo Corradini
Journal: Blood (2010)
Interim safety and clinical activity in patients with advanced NSCLC from a multi-cohort phase 1 study of ramucirumab (R) plus pembrolizumab (P)
Authors: R.S. Herbst, J. Martin-Liberal, E. Calvo, N. Isambert, J.C. Bendell, P. Cassier, J.L. Perez-Gracia, J. Yang, J. Rege, G. Mi, D. Ferry, L. Paz-Ares
Journal: Annals of Oncology (2016)