tbuckley/cabot-search huggingface dataset:
Characterization of a novel mutation in fibrolamellar hepatocellular carcinoma.
Authors: Kevin M Riggle, Heidi Kenerson, Machiko Kazami, Renay Bauer, Raymond Sze Yeung, Kimberly J Riehle
Journal: Journal of Clinical Oncology (2015)

284 Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a subtype of HCC occurring in children and young adults in the absence of underlying liver disease. Currently, there is no effective therapy for unresectable or metastatic FL-HCC. Recent genomic analysis identified a consistent mutation in FL-HCC involving a deletion on chromosome 19 resulting in a chimeric transcript containing the 5’-region of a heat shock protein (DNAJB1) fused to the catalytic subunit of protein kinase A (PRKACA). We sought to characterize the resultant protein and its effects on PKA activity in human FL-HCC. Methods: We prepared tissue lysates from four snap-frozen FL-HCC samples with paired, non-tumor liver as well as adult HCCs. PKA activity was determined via a radioactive kinase assay in the presence and absence of cAMP, a PKA activator. RNA was extracted using TRIZOL, and used for qRT-PCR. Triple immuno-fluorescent labeling was performed using antibodies to PRKACA, PKA RIIα, and a nuclear marker, DRAQ5. Results: We found that expression of the chimeric transcript was increased 40-fold in FL-HCC compared to normal liver, and was significantly higher than that of wild-type DNAJB1 and PRKACA in FL-HCC. The corresponding mutant protein was highly expressed in the tumors and was unique to FL-HCC. Basal PKA activities from freshly lysed tumors and paired livers were not significantly different, but cAMP-stimulated PKA activity was significantly higher in FL-HCC tumors when compared to normal liver. Using multi-color immuno-fluorescence we detected mutant DNAJB1-PRKACA within the nucleus, while wild-type PRKACA localizes to the cytoplasm. Conclusions: The expression of DNAJB1-PRKACA is unique to FL-HCC and not found in classic forms of HCC. Markedly elevated expression of the mutant transcript is indicative of dysregulated DNAJB1 promoter activity. PKA activity in FL-HCCs remains cAMP-dependent, but is greatly enhanced in the presence of cAMP; this could reflect an altered intrinsic activity of the mutant protein and/or elevated expression. Further, the mutant protein showed aberrant localization to the nucleus. These findings suggest that DNAJB1-PRKACA in FL-HCC leads to over-activation of PKA, which may contribute to tumor development.
A phase II study of neoadjuvant chemotherapy with a modified FOLFOX6 regimen for locally advanced gastric cancer.
Authors: Xiang Wang, Lin Zhao, Hongfeng Liu, Chunmei Bai, Xiaoyi Li
Journal: Journal of Clinical Oncology (2016)

81 Background: The aim of this study was to evaluate the efficacy and safety of neoadjuvant chemotherapy with the mFOLFOX6 regimen in gastric cancer patients. Methods: This study was a single-arm phase II study. 73 patients with histologically confirmed locally advanced gastric cancer (T2-T4 or N+) were enrolled. The patients were administered the mFOLFOX6 regimen for 3 cycles. Surgery was scheduled 3-4 weeks after the completion of the chemotherapy. Postoperative chemotherapy began 4 weeks after surgery, and the program choice was based on the results of patients’ clinical/pathological evaluations. Perioperative efficacy, toxicity, effects of surgery, postoperative observation, and prognosis were studied. Survival analysis was performed to identify the relationship between the response and outcome and to identify factors predictive of OS. Results: 73 patients received the neoadjuvant chemotherapy, and 67 (91.8%) completed all of the preoperative cycles, with grade 3-4 toxicity arising in 33.0%. Surgery was performed in 71 (97.3%) patients, and radical resection was achieved in 67 (91.8%) patients. Postoperative chemotherapy started in 63 (88.7%) patients. The radiology response rate of chemotherapy was 45.8%. Among the patients who underwent radical surgery, pT downstaging was observed in 22 (32.8%) patients and pN downstaging was observed in 17 (25.4%) patients. All of the patients showed different levels of histological regression of the primary tumour, with a ≥ 50% regression rate of 49.2% and a pCR rate of 3.0%. Univariate analysis identified factors that were associated with OS, including local tumour infiltration, Lauren classification, pre-chemotherapy N stage, ypTNM stage, and pathologic regression rate (GHR)( ≥ 2/3/ &lt; 2/3, ≥ 50%/ &lt; 50%). Multivariate analysis identified both ypTNM stage and Lauren classification as independent predictors of survival. Conclusions: The mFOLFOX6 regimen was very effective and well-tolerated as a neoadjuvant chemotherapy for locally advanced gastric cancer. The ypTNM stage could serve as an independent predictor of survival. GHR ≥ 50% / &lt; 50% could be used as a surrogate marker to guide the selection of a postoperative chemotherapy regimen. Clinical trial information: NCT02226380.
Cost Effectiveness of Screening Patients With Gastroesophageal Reflux Disease for Barrett’s Esophagus With a Minimally Invasive Cell Sampling Device
Authors: Curtis R. Heberle, Amir-Houshang Omidvari, Ayman Ali, Sonja Kroep, Chung Yin Kong, John M. Inadomi, Joel H. Rubenstein, Angela C. Tramontano, Emily C. Dowling, William D. Hazelton, E. Georg Luebeck, Iris Lansdorp-Vogelaar, Chin Hur
Journal: Clinical Gastroenterology and Hepatology (2017)
Identification of Non-Permissive HLA Allele Mismatch Combinations and Amino Acid Substitution Responsible for Acute Graft-Versus-Host Disease in Unrelated Allogeneic Bone Marrow Transplantation.
Authors: Yasuo Morishima, Takakazu Kawase, Keitaro Matsuo, Koichi Kashiwase, Hidetoshi Inoko, Hiroh Saji, Shunichi Kato, Takeo Juji, Yoshihisa Kodera, Takehiko Sasazuki
Journal: Blood (2006)
Bcr-Abl Kinase Domain Mutations in Imatinib and in Second-Generation Tyrosine Kinase Inhibitor Eras: Seven Years of Mutation Analysis, a Report by the GIMEMA CML Working Party
Authors: Simona Soverini, Alessandra Gnani, Sabrina Colarossi, Fausto Castagnetti, Ilaria Iacobucci, Massimo Breccia, Elisabetta Abruzzese, Fabrizio Pane, Giuseppe Saglio, Domenico Russo, Giorgina Specchia, Patrizia Pregno, Federica Sorà, Mario Tiribelli, Francesca Palandri, Gabriele Gugliotta, Marilina Amabile, Gianantonio Rosti, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2010)
Blinded independent radiologic review (BIRR) versus investigator radiologic evaluation (IRE) for response assessment in metastatic colorectal cancer (mCRC): Systematic review and meta-analysis.
Authors: J. P. S. N. Lima, F. M. Carcano, F. H. Souza, L. V. dos Santos
Journal: Journal of Clinical Oncology (2011)

2559 Background: Randomized controlled trials (RCT) provide the most reliable evidence about therapeutic interventions. However, RCTs are still in risk of some bias, like assessment bias. In order to reduce assessment bias, BIRR has been frequently used in clinical research. Despite the widespread use of BIRR, its real impact on bias reduction is fairly unknown. We performed a systematic review and meta-analysis to evaluate the impact of BIRR on response evaluation in mCRC. Methods: RCT testing any drug therapy in mCRC was eligible if overall response rate (ORR) data from BIRR and IRE were presented. Medline, Embase, CENTRAL, Clinicaltrials.gov, ASCO, and ESMO proceedings were searched. Random-effects model were used in calculations. Heterogeneity was expressed as I². Risk ratio (RR) and 95% confidence intervals (95%CI) were computed for BIRR and IRE data. Interaction tests were used to compare BIRR and IRE results. Ratios between response rates in experimental arms in BIRR and IRE (experRR) and control arms in BIRR and IRE (contRR) were also calculated. Results: 12 RCT (5189 patients) provided ORR data. Overall response rate RR in BIRR was 1.17 (95% CI 1.10, 1.25) while overall response rate RR in IRE was 1.19 (95% CI 1.11, 1.27). Interaction test showed no difference in ORR assessments between BIRR and IRE (P=0.17). The experRR (RR 0.88; 95%CI 0.79, 0.99) and contRR (RR 0.86; 95%CI 0.76, 0.97) showed that BIRR decreased the frequency of responses in experimental and control arms in a similar fashion, differently from previously hypothesized (Dodd et al., Biometrics 2011). Conclusions: In this large sample of trials, BIRR seemed to reduce the response rate in a similar amount in both control and experimental arms. These results suggest that BIRR may not improve reliability or assessment bias of randomized controlled trials. However, BIRR may be important in studies whose endpoints are response rates, such as phase II trials. Any impact of BIRR in local radiologist’s behavior, like “audit bias”, could not be evaluated and a prospective study is mandatory.
Evaluation of combination treatment with a BRAF inhibitor (BMS-908662) and CTLA-4 monoclonal antibody in preclinical models.
Authors: M. Jure-Kunkel, G. Masters, E. Girit, G. Dito, T. Wong, J. Wigginton, A. K. Gupta, J. Hunt
Journal: Journal of Clinical Oncology (2011)

e13055 Background: The antitumor activity and immunomodulatory effect of an ipilimumab homolog antibody in combination with BMS-908662, a selective RAF inhibitor, were assessed in preclinical models. Methods: Efficacy studies were conducted in the CT26 colon carcinoma and SA1N fibrosarcoma tumor models. Combination therapy was evaluated following concurrent or sequential dosing regimens. In addition, the effect of both agents on antigen-specific T cell expansion was evaluated in an ovalbumin antigen challenge model. Results: CT26 tumor model: As monotherapy, both BMS-908662 and the CTLA-4 antibody demonstrated anti-cancer activity. BMS-908662, 100 mg/kg every other day for 4 or 7 doses, demonstrated 78% and 73% tumor growth inhibition (TGI) respectively. The CTLA-4 mAb resulted in 97% TGI when dosing started on day 4. An enhanced antitumor effect was observed with combination dosing, (concurrent schedule - beginning on day 4), with higher number of tumor-free mice at the end of the study (10, 40 and 100% tumor-free mice for BMS-908662, CTLA-4 mAb and the combination treatment respectively). In the sequential dosing regimen, BMS-908662 (100 mg/kg) was administered for 4 doses every other day followed by CTLA-4 mAb. This dosing regimen also resulted in enhanced antitumor activity compared to single agent activity (tumor-free mice = 33, 10 and 63% for BMS-908662, CTLA-4 mAb and the combination treatment respectively). SA1N tumor model, sequential dosing of both agents resulted in 50% of mice with complete regressions compared to 0 for CTLA-4 mAb and 12.5% for BMS-908662. There was no indication of increased toxicity from combining the two agents at the doses tested. Furthermore, combination of both agents resulted in a significant expansion of antigen-specific T cells (p<0.05) in an ovalbumin antigen challenge model. Conclusions: Results from these studies support the rationale to further explore this combination in clinical trials.
Modification of the Psoriatic Arthritis Disease Activity Score (PASDAS)
Authors: Philip S Helliwell, Robin Waxman
Journal: Annals of the Rheumatic Diseases (2017)

Psoriatic arthritis is a complex heterogeneous disease manifesting with skin disease and a number of musculoskeletal abnormalities including arthritis, enthesitis, dactylitis and spondylitis. While not all of these manifestations are present in every patient, assessment of disease activity should account for these domains. To combine these domains into one composite score has been challenging but several have been developed. The Psoriatic Arthritis Disease Activity Score (PASDAS) was developed as part of an international Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) exercise.1 This measure includes physician-reported and patient-reported outcome measures combined into a composite index. The PASDAS requires the patient to complete a visual analogue scale and the short form 36 (SF36). The latter consists of 36 questions covering domains of physical and mental health. A shorter, 12 …
Outcomes and Immune Phenotype Recovery after Double Cord Blood Transplantation in Patients with High Risk Hematological Diseases
Authors: Annalisa Ruggeri, Regis Peffault de Latour, Maryvonnick Carmagnat, Marie Robin, Adrienne Madureira, Jerome Larghero, Richard Traineau, Patricia Ribaud, Cristele Ferry, Agnes Devergie, Claire Rabian, Antoine Toubert, Eliane Gluckman, Gerard Socié, Vanderson Rocha
Journal: Blood (2008)
Turnaround time for treatment of patients with colorectal cancer
Authors: S. F. Ali, M. F. Ali, T. Ahmed, A. G. Mundia, K. Seiter, S. S. Shah
Journal: Journal of Clinical Oncology (2008)

17548 Background: Colorectal cancer is one of the leading causes of deaths in the United States. Depending on cancer staging and other co-morbidities, patients require either first, second, or third line chemotherapy regimens, which are paid for through a health insurance plan. Based on insurance plan policies and criteria, the turnaround time for treatment can take weeks before treatment initiation. Chemotherapy induced neutropenia and/or anemia may result from chemotherapy. Methods: A retrospective study was performed on patient charts in which 180 patients, in groups of 20, represented six of the major insurance companies seen in the Westchester Hematology/Oncology Private Practice. These charts were analyzed to calculate the average turnaround time for treatment administration and the correlation between this turnaround time and the cost of treatment. Results: Insurance companies which required specialty pharmacies and preauthorizations such as AETNA, Blue Cross Blue Shield (BCBS), and HIP had the longest turnaround times for treatment, averaging from 9–19 days for all types of treatment. This was followed by insurance companies that required patients to obtain treatment from a local pharmacy such as UHS and GHI, averaging from 6–15 days for all types of treatment. Medicare, which allowed patients to obtain treatment directly from the office had the shortest turnaround time in treatment, averaging from 3–11 days. Patients with chemotherapy induced neutropenia/anemia were forced to stop treatment until medications were obtained and bloodwork returned to normal, further delaying the turnaround time for subsequent treatments. In addition there was a direct correlation between the turnaround time for treatment and the cost of treatment for all insurance companies. Conclusion: Based on insurance policy, the initiation of chemotherapy treatment can be delayed. Studies indicate that delays in treatment can increase the log growth of cancer cells. Patients and physicians are forced to wait, appeal and sometimes fight with the insurance company for treatment reimbursement. In addition, chemotherapy induced neutropenia/anemia requires treatment to be halted. Studies indicate that such dose delays may allow more tumor regrowth between cycles. No significant financial relationships to disclose.
Long-term Results of a Comparative PET/CT and PET/MRI Study of 11C-Acetate and 18F-Fluorocholine for Restaging of Early Recurrent Prostate Cancer
Authors: Giorgio Lamanna, Claire Tabouret-Viaud, Olivier Rager, Sandra Jorcano, Hans-Joerg Vees, Yann Seimbille, Habib Zaidi, Osman Ratib, Franz Buchegger, Raymond Miralbell, Thomas Zilli, Valentina Garibotto
Journal: Clinical Nuclear Medicine (2017)

The aims of this study were to assess the intraindividual performance of F-fluorocholine (FCH) and C-acetate (ACE) PET studies for restaging of recurrent prostate cancer (PCa), to correlate PET findings with long-term clinical and imaging follow-up, and to evaluate the impact of PET results on patient management.Thirty-three PCa patients relapsing after radical prostatectomy (n = 10, prostate-specific antigen [PSA] ≤3 ng/mL), primary radiotherapy (n = 8, prostate-specific antigen ≤5 ng/mL), or radical prostatectomy + salvage radiotherapy (n = 15) underwent ACE and FCH PET-CT (n = 29) or PET-MRI (n = 4) studies in a randomized sequence 0 to 21 days apart.The detection rate for ACE was 66% and for FCH was 60%. Results were concordant in 79% of the cases (26/33) and discordant in 21% (retroperitoneal, n = 5; pararectal, n = 1; and external iliac nodes, n = 1). After a median FU of 41 months (n = 32, 1 patient lost to FU), the site of relapse was correctly identified by ACE and FCH in 53% (17/32) and 47% (15/32) of the patients, respectively (2 M1a patients ACE+/FCH-), whereas in 6 of 32 patients the relapse was not localized. Treatment approach was changed in 11 (34.4%) of 32 patients and 9 (28%) of 32 patients restaged with ACE and FCH PET, respectively.In early recurrent PCa, ACE and FCH showed minor discrepancies, limited to nodal staging and mainly in the retroperitoneal area, with true positivity of PET findings confirmed in half of the cases during FU. Treatment approach turned out to be influenced by ACE or FCH PET studies in one third of the patients.
Epigentic mechanisms involved in the differential expression of <i>MDR1</i> between gastric and colon cancer cells
Authors: K. J. Kim, Y. D. Min, T. B. Lee, C. H. Choi
Journal: Journal of Clinical Oncology (2005)

9708 Background: The multidrug resistance (MDR) of tumor cells to anticancer drugs remains a major cause of treatment failure in cancer patients. The overexpression of P-glycopotein (Pgp), an MDR1 gene product, confers MDR to cancer cells. Methods: To explore the mechanisms and roles of differential MDR1 mRNA expression in gastric and colon cancer cells, its chemosensitivity, function and epigenetic regulation of gene expression in 10 gastric cancer cell lines (SNU-1, -5, -16, -216, -484, -601, -620, -638, -668 and -719) and 9 colon cancer cell lines (SNU-C1, -C4, -C5, COLO320HSR, LoVo, DLD-1, HT-29, HCT-8 and HCT-116) were compared. Results: The RT-PCR assay revealed that MDR1 mRNAs in 7 colon cancer cell lines except SNU-C5 and HT-29 were variously expressed whereas those in gastric cancer cell lines were significantly lower and even not expressed in SNU-16 than those of colon cancer cell lines. The MTT assay showed comparative resistance of COLO320HSR (high level of MDR1 mRNA expression) to paclitaxel with that of SNU-C5 (low level of its expression). Flow cytometry showed that decreased rhodamine accumulation of COLO320HSR was increased by PSC833, a Pgp inhibitor, suggesting that Pgp works functionally as an efflux pump. The methylation specific PCR indicated that SNU-1, -5, -16, -216, -601, -620, -638 -668 and -719 except for SNU-484 in gastric cancer cells and SNU-C5, COLO320HSR, HT-29, HCT-116 in colon cancer cells were hypermethylated. MDR1 mRNA levels of SNU-5, -601, -668 and -719 in gastric cancer cells more increased when treated with 5-aza-2’-deoxycytidine (a methyltransferase inhibitor) and/or tricostatin A (histone deacetylase inhibitor), respectively. Conclusions: These results suggest that MDR1/Pgp plays more important roles in colon cancer cells than gastric cancer cells and their differential expression of MDR1 was regulated by epigenetic mechanisms. No significant financial relationships to disclose.
Postoperative adjuvant 5-fluorouracil, cisplatin (FP) before and after chemoradiation with capecitabine versus FP alone in completely resected locally advanced gastric cancer
Authors: H.-C. Kwon, M. C. Kim, S. Y. Oh, S.-H. Kim, J.-S. Kim, H. S. Lee, G. J. Jung, H.-J. Kim
Journal: Journal of Clinical Oncology (2005)

4146 Background: Gastric cancer is the most common cancer in Korea. Adjuvant chemoradiation has become a standard of care in United States. We attempted to evaluate the efficacy and toxicity of FP before and after postoperative chemoradiation versus FP alone in patients with locally advanced gastric cancer. Methods: Patients with gastric cancer staged IIIA to IV-M0 were treated with chemoradiation and FP (arm A) or FP alone (arm B) after curative resection with extensive (D2) lymph node dissection. Arm A consisted of one cycle of FP (5-FU 1000 mg/m2 continuous infusion on day 1–5, cisplatin 60 mg/m2 on day 1) followed by 4,500 cGY (180 cGy/day) to RT field with capecitabine (1,650 mg/m2/day throughout radiation). One month after completion of radiotherapy, patients received three additional cycles of FP every 3 weeks. Arm B consisted of six cycles of FP. Results: Eighty-one patients were enrolled (33;arm A, 48;arm B), and median follow-up duration was 14.7 months (range 1–34.7). A total 9 patients (27.3%) did not complete all planned therapy in arm A, 13 patients (27.1%) in arm B. There was no significant difference in 2-year survival (85.4% vs 78.7%, respectively; P = 0.48), or 2-year disease free survival (69.5% vs. 60.4%, respectively; P = 0.64) between arm A and B. Six patients (18.1%) have relapsed (3; liver, 2; peritoneum, 1; ovary) in arm A, and 11 patients (22.9%) have relapsed (4;liver, 3;peritoneum, 2;bone, 1;ovary, lymph nodes) in arm B. Grade 3/4 neurtopenia occurred in 48.5% in arm A and 22.9% in arm B. Grade 3 nausea/vomiting occurred in 6% in arm A and 14.6% in arm B. There was no grade 3/4 hand foot syndrome, and there has been no treatment related deaths. Conclusions: These preliminary results suggest that postoperative adjuvant chemoradiation and chemotherapy versus chemotherapy alone has similar efficacy in gastric cancer patients who have undergone a D2 dissection. Longer follow up and further studies are needed to evaluate efficacy. No significant financial relationships to disclose.
Outcomes of adjuvant platinum-based chemotherapy or radiation therapy in completely resected stage I-IV uterine carcinosarcoma (uCS)
Authors: V. Makker, N. R. Abu-Rustum, C. A. Aghajanian, M. L. Hensley
Journal: Journal of Clinical Oncology (2008)

5560 Background: GOG 150, a phase III trial of whole abdominal irradiation (WAI) v. cisplatin-ifosfamide-mesna (CIM) as post- resection therapy for completely resected stages I-IV uCS patients, required 11 years to accrue 206 patients. 3 year (y) Overall Survival (OS) was approximately 54% with CIM v. 43% with RT. We aimed to determine whether progression free survival (PFS) and OS in a cohort of patients who would have met GOG 150 eligibility criteria and received either platinum-based chemotherapy with or without pelvic RT or intravaginal RT (Chemo±RT), or pelvic RT or WAI ± IVRT (RT alone) was similar to GOG outcomes, in an era when most patients received paclitaxel- carboplatin (PC). Methods: MSKCC electronic medical records from 8/1/1995 to 10/3/2007 were reviewed for pt age, diagnosis date, debulking status, stage, treatment, dates of progression and death, and site of first recurrence. PFS and OS by stage (I/II v. III/IV) and by adjuvant treatment (Chemo± RT v. RT alone) using landmark analyses were determined. Results: 46 patients met study criteria (58 pts were identified; 9 excluded for no treatment or only IVRT; 3 for progression within 8 weeks of surgery). 35/46 patients received adjuvant chemotherapy: 21/35 (60%) PC; 7/35 (20%) ifosfamide-platinum; 7/35 (20%) other chemo. FIGO stage was: I = 14 (30%); II = 4 (9%); III = 20 (44%); IV = 8 (17%). 3 y PFS for stages I-II was 43% v. 14% for stages III-IV (HR = 1.98 [0.9–4.33]); p = 0.082. 3 y OS for stages I-II was 68% and v. 55% for stages III-IV (HR = 1.26 [0.47–3.41]); p = 0.648. 3 y OS for Chemo±Pelvic RT±IVRT was 66% v. 34% for RT alone (HR = 2.02 [0.77–5.33]); p = 0.146. 3y PFS by treatment group is in the Table. Conclusions: PC has become a common adjuvant chemotherapy for uterine carcinosarcoma. Our data confirm recent results which demonstrated a superior PFS and OS for pts treated with chemotherapy, even when the majority received PC. Landmark analysis of PFS stratified by treatment (N=46) Variable N %PF 3Y PFS Rate (95%CI) Hazard Ratio P-value Treatment Group Chemo±RT 35 51% 35% (16∼54%) 0.164 RT alone 11 9% 9% (1∼33%) 1.74 (0.79∼3.85) No significant financial relationships to disclose.