tbuckley/cabot-search huggingface dataset:
Do recurrent and de novo metastatic biliary tract cancer patients have the same outcome on treatment?
Authors: Mairead G McNamara, Priya Aneja, Manjula Maganti, Anne M. Horgan, Sean P. Cleary, Jennifer J. Knox
Journal: Journal of Clinical Oncology (2015)

351 Background: Biliary tract cancers (BTCs) include cholangiocarcinoma, which refers to cancers arising in the intrahepatic, perihilar or distal biliary tree, ampulla of vater and gallbladder carcinoma. Even after complete surgical resection, a large number of BTC patients develop recurrence. Whether recurrence after surgery and de novo metastatic BTC should have comparable stratification in first-line palliative systemic therapy clinical studies is unknown. Methods: 480 patients who received palliative chemotherapy as first-line treatment for advanced BTC between January 1987 and May 2014 in Princess Margaret Cancer Centre, Toronto were reviewed. Probability of overall survival (OS) was estimated using the Kaplan-Meier method, and independent prognostic factors for OS were identified using the multivariable Cox proportional hazard model. Results: There were 171 recurrent and 309 de novo metastatic patients. Median age at diagnosis was 62 years, performance status&lt;2; 436 (91%) patients, male; 262 (55%). In the recurrent group, 91 (53%) had indwelling stents, ampulla of vater; 50 (29%), gallbladder; 29 (17%), cholangiocarcinoma; 92 (54%). In the de novo metastatic group, 185 (60%) had indwelling stents, primary site was ampulla of vater; 16 (5%), gallbladder; 94 (30%), cholangiocarcinoma; 199 (65%). Systemic treatment received was gemcitabine/platinum doublet in 134 (28%), gemcitabine/5-FU doublet; 186 (39%), gemcitabine; 97 (20%), other; 63 (20%). Median OS for the recurrent group who received first-line palliative chemotherapy was 15.6 months (95% confidence interval [CI] 13.5-18.0) and 14.4 months (95% CI 12.0-16.0) in the de novo metastatic group. Multivariable analysis for OS revealed that gallbladder as the primary site (P=0.03) and ECOG performance status ≥2 (P=0.001) were prognostic for worse OS. De novo metastatic status was not prognostic for worse OS compared with recurrent status (Hazard ratio 1.1, 95% CI 0.82-1.50, P=0.51). Conclusions: Similar treatment of patients with recurrent disease after surgery and de novo metastatic BTC, with first-line palliative chemotherapy is acceptable.
Is the incidence of anal canal cancers different in Moslem societies?
Authors: D. Cabuk, P. F. Yumuk, U. Abacioglu, G. Demir, F. Dane, M. Gumus, M. Ozguroglu, M. Ekenel, G. Basaran, N. S. Turhal
Journal: Journal of Clinical Oncology (2004)

4233 Background: In the western world, cancers of the anal region account for 1% to 2% of all colon cancers and 3.9% of all anorectal carcinomas. The majority of these patients (75% to 80%) have squamous cell carcinomas and the rest have mainly adenocarcinomas. Many medical oncologists in Turkey state in their private communications that the anal cancers are rare in the Moslem world, due to different sanitary habits of these societies. There are no tumor registries established in the Moslem world to confirm this. In order to study this we reviewed local tumor registries in two university medical centers with respected oncological reputation. Methods: Marmara and Cerrahpasa University Hospital Medical Oncology Divisions' tumor registries are studied between 1990 and 2003. All patients whether they have received any chemo-radiotherapy or not are included in the tally. Results: There are 798 patients with large bowel carcinomas during that period and 9 (1.12%) of these patients have squamous cell carcinomas of anal canal. Conclusion: Even though sanitary behaviors are different in Moslem societies like our country, it appears that the ratio of anal to colorectal cancers are no different than what is reported in the western literature. No significant financial relationships to disclose.
A phase II study of the antisense oligonucleotide GTI-2040 plus docetaxel and prednisone as first line treatment in hormone refractory prostate cancer (HRPC)
Authors: S. S. Sridhar, C. M. Canil, S. J. Hotte, K. Chi, S. Ernst, G. R. Pond, C. Dick, J. A. Zwiebel, M. J. Moore
Journal: Journal of Clinical Oncology (2006)

13015 Background: Despite initial responses to chemotherapy, median survival in HRPC remains a dismal 18 mos. Novel therapeutic approaches are clearly needed. The enzyme ribonucleotide reductase (RNR) composed of 2 subunits, R1 and R2 is essential for DNA synthesis and repair. The R2 subunit is often overexpressed in tumors increasing their malignant potential and promoting drug resistance. GTI-2040 (Lorus Therapeutics, Canada) is an antisense oligonucleotide to the R2 subunit downregulating its expression. In preclinical studies, GTI-2040 has shown antitumor activity in prostate cancer xenografts, synergy and non-overlapping toxicity with the taxanes. It is therefore a rational choice for combination with docetaxel in HRPC. Objectives: To determine efficacy of this regimen using PSA response rate. Secondary objectives include: duration of response, TTP, objective tumor response rate, safety and tolerability. Pharmacokinetic (PK) studies will be performed. PBMC will be used to determine RNR activity and R2 subunit quantitation. Methods: HRPC patients with PS 0–2, adequate organ function and no prior chemotherapy were treated with GTI-2040 5mg/kg/d continuous infusion for 14d, docetaxel 75 mg/m2 IV every 21d, and prednisone 5mg twice daily. Results: Twenty-two pts in 5 centers have been enrolled. Pts have received a total of 107 cycles to date. Median age 63 (52–77); median baseline PSA 140 (26–1256); ECOG 0:1:2: 14:7:1; prior radiotherapy in 14 pts. Pts received a median of 5 cycles (2–10). Grade 3/4 hematologic toxicities were lymphophenia (10pts), leukopenia (7pts), and neutropenia (7pts). Anemia (any grade) was seen in 19 pts across 92 cycles. Most frequent non-hematologic toxicities were fatigue and pain. PSA responses seen in 9/22 pts. Objective tumor response:1 PR, 9 SD, 3 PD, 3 off due to toxicity prior to objective response measurement, 3 no measureable lesions, 3 to be assessed. 19 pts off treatment: 9 PD, 4 toxicity (1 toxic death), 2 completed 10 cycles, 2 at investigator’s discretion and 2 withdrew consent. Three pts remain on study. Median TTP estimated at 17 wks. Accrual has been sufficient to meet stage 1 requirements. Final response, toxicity, pK, RNR and R2 subunit analysis will be available and presented. No significant financial relationships to disclose.
Ad-ISF35-transduced autologous cells promote in vitro and in vivo chemosensitization in patients with 17p-/P53-defective chronic lymphocytic leukemia
Authors: J. Melo-Cardenas, J. E. Castro, B. Cox, J. D. Sandoval-Sus, D. Darrah, M. Urquiza, C. E. Prussak, T. J. Kipps
Journal: Journal of Clinical Oncology (2009)

e14552 Background: Transduction of chronic lymphocytic leukemia (CLL) cells with a replication-defective adenovirus (Ad) encoding recombinant CD154 (Ad-ISF35) induces expression of death receptors and Bid via a P53-independent pathway involving induction of P73. Induction of P73 significantly enhances the sensitivity of P53-defective CLL cells to “P53-dependent” drugs, such as Fludarabine (F-ara-A). Patients with P53-defective CLL who received iv infusions of autologous Ad-ISF35-transduced CLL cells were observed to achieve complete remissions (CR) with subsequent treatment using F-ara-A based treatment regimens, suggesting Ad-ISF35 could sensitize P53-defective CLL to chemotherapy. Methods: We examined patients with drug-resistant and/or P53-defective CLL before and after iv infusions of autologous Ad-ISF35-transduced CLL cells who were enrolled in a phase I study examining whether such treatment could sensitize patients to a truncated fludarabine, cyclophosphamide and rituximab (FCR) regimen. We examined CLL cells for sensitivity to F-ara-A in vitro, expression of CD95, DR5, Bid, and P73 and correlated these with the response to treatment in vivo. Results: P53-defective CLL cells were resistant to F-ara-A induced apoptosis with IC50 &gt; 10μM prior to treatment. CLL cells collected from patients≥24 hours after IV infusion of autologous Ad-ISF35-trasduced CLL cells became sensitive to the cytotoxic effects of F-ara-A, with IC50 0.3–1 μM. Enhanced sensitivity to F-ara-A was associated with induced expression of Bid, DR5, CD95, and P73 by circulating CLL cells, an effect lasting≥2 weeks following iv infusion. Consistent with this, we observed complete resolution in lymphocytosis, lymphadenopathy and splenomegaly following 1 cycle of FCR administered 2 weeks after 3 biweekly infusions of Ad-ISF35- transduced CLL cells. Conclusions: IV infusion of autologous Ad-ISF35-transduced CLL cells can induce de novo, systemic expression of death receptors and Bid on bystander CLL cells, which is associated with enhanced sensitivity of P53-defective CLL to the cytotoxic effects of standard chemotherapy [Table: see text]
GATA-1 Interferes with Monopoiesis by Blocking a Positive Regulatory Circuit Involving VDR and PU.1 - Results from a Retroviral Dominant Effector Screen.
Authors: Sabine Taschner, Florian Gobel, Mario Kumerz Mag, Almut Jorgl, Susanne Richter, Herbert Strobl
Journal: Blood (2007)
Loss of Mismatched HLA as a Mechanism of Leukemia Immune Escape in Family Haploidentical and Unrelated HSCT: Analysis of 103 Transplants From Alternative Donors.
Authors: Luca Vago, Maria Teresa Lupo Stanghellini, Daniela Clerici, Alessandro Crotta, Carlo Messina, Barbara Forno, Benedetta Mazzi, Monica Zanussi, Andrea Assanelli, Sarah Marktel, Magda Marcatti, Consuelo Corti, Massimo Bernardi, Jacopo Peccatori, Silvano Rossini, Maurizio Ferrari, Claudio Bordignon, Chiara Bonini, Katharina Fleischhauer, Fabio Ciceri
Journal: Blood (2009)
Is there any difference between microscopic residual disease (pTm) and no invasive disease (pT0) in the breast when there is residual disease in the axilla after primary chemotherapy for breast cancer (BC)? Results of a multicenter study
Authors: S. Barni, M. T. Ionta, M. E. Cazzaniga, F. Atzori, F. Petrelli, M. Murru, M. Cabiddu, D. Guerzoni, L. Minerba, B. Massidda
Journal: Journal of Clinical Oncology (2007)

11069 Background: Several studies have demonstrated the importance of achieving pCR both in the breast and axilla, in terms of DFS and OS. We previously demonstrated that no difference exists between microscopic residual (pTm) and no invasive residual (pT0) tumour in the breast in terms of DFS and OS in breast cancer (BC) patients (pts) following primary chemotherapy (CHT). Nevertheless, when pN0 is achieved, we observed a statistical significant advantage for pT0 in comparison to pTm pts (DFS 94.7% vs 80%, p=0.03; OS 100% vs 86%, p=0.08). Aim of the present study was to investigate the clinical significance of pTm in the breast when there is residual tumour in the axilla. Methods: We analysed 48 out of 287 pts with clinical T 2–4 BC, who achieved pCR, according to Sataloff’s classification, following different kinds of neoadjuvant CHT. One pt was considered not valuable for clinical outcomes, because lost to follow up. Median age was 47 years (29–68), clinical TN stage was T4 in approximately half of the pts (22/48, 45.8%) and N+ in 11/48 (22.9%). Hormone receptor status was ER- in 20 pts (41.7%) and PR- in 26 (54.2%). All pts received anthracycline-based neoadjuvant CHT, even standard (Q21 days) or intensified (Q14). Median number of administered cycles was 3 (2–6). Median follow up was 89 months (9–189). Results: Thirteen pts (27.6%) had residual disease in the axilla at the end of primary CHT, of whom 6 achieved pT0 and 7 pTm in the breast. Surprisingly, pTm pts had a significant better DFS and OS in comparison to pT0 pts. Results are shown in Table 1 . Conclusions: Our data indicate that the achievement of pT0 in the breast is not of clinical significance when there is residual tumour in the axilla. These results, even if affected by the small number of pts, could be explained by the fact that less aggressive treatments have been delivered to pT0 pts due to the complete clearance of the tumour. [Table: see text] No significant financial relationships to disclose.
Neoadjuvant imatinib and organ preservation in locally advanced gastrointestinal stromal tumors (GIST)
Authors: P. Hohenberger, O. Oladeji, T. Licht, A. Dimitrakopoulou-Strauss, J. Jakob, D. Pink, M. Schwarzbach, P. Ströbel, P. Reichardt, E. Wardelmann
Journal: Journal of Clinical Oncology (2009)

10550 Background: We assessed the outcome of patients with locally advanced gastrointestinal stromal tumors (GIST) undergoing preoperative therapy with imatinib. Methods: 36 patients with biopsy proven GIST (23 f, 13 m, median age 58 (27–85) yrs, 31 primary tumors, 5 local recurrences) of the esophagus/EGJ (n=5), stomach (n=17), duodenum (n=2), small bowel (n=3), or rectum (n=9) were treated with imatinib 400mg/d for 6 mos. preop. Six pts had been found unresectable at exploratory lap. and no pt. had signs of metastases on CT/MRI and/or FDG-PET. Average tumor size was 10.5 cm (4–28 cm). According to Consensus two tumors were low risk, 11 intermediate, and 23 were high risk for aggressive behaviour. 33 pts were symptomatic. Extent of surgery, local outcome, morbidity and response to therapy were analyzed; median follow-up is 22 mos. Results: Median treatment duration was 11 mos. (range 2–31 mos). Successful dose adjustment for exon 9 mutation to 800 mg imatinib/d was used in two pts. 33 pts. completed the treatment schedule, two died from unrelated disease, another one had to be operated for tumor rupture. Of the remaining 33, median tumor size shrank to 55 mm. Two elderly patients refused surgery and continued with the drug; one pt. was found still unresectable. Complete tumor removal was possible in 28 pts without operative mortality, but two pts showed previously undetected peritoneal spread (R2 resection). Histologically, one pCR and 11 near CR/good PRs were found. The extent of resection found 5 of 6 inoperable pts now resectable and in 21/25 pts a less extensive procedure could be performed in comparison to recommendations by previous tumor boards (segmental gastric resection for gastrectomy, avoidance of pancreatectomy, transanal resection instead of colo-anal anastomosis). Two local recurrences were detected at 31 and 44 mos. postop. Conclusions: Locoregionally advanced GIST can be treated successfully with upfront imatinib at 400mg/ (800 mg in exon 9 mutation). Substantial tumor shrinkage facilitates radical but conservative surgery and results in organ-preservation in the overwhelming majority of patients. PET monitoring proved very helpful and added to CT/MRI evaluation. Long-term results on survival and metastatic spread have to be awaited. [Table: see text]
Response to High Dose Imatinib and Long-Term Outcome in Children and Adolescents with Previously Untreated Chronic Myeloid Leukemia in Chronic Phase. the Italian Experience
Authors: Fiorina Giona, Maria Caterina Putti, Giuseppe Menna, Concetta Micalizzi, Nicola Santoro, Grazia Iaria, Saverio Ladogana, Roberta Burnelli, Caterina Consarino, Maria Luisa Moleti, Sabrina Mariani, Daniela De Benedittis, Deborah Marzella, Stefania Varotto, Francesca Tucci, Mauro Nanni, Chiara Messina, Daniela Diverio, Andrea Biondi, Andrea Pession, Marco Zecca, Franco Locatelli, Giuseppe Saglio, Robin Foà
Journal: Blood (2014)
Src kinase activity in early breast cancer (EBC): A quantitative luminometric and immunohistochemical (IHC) approach
Authors: O. Young, R. J. Jones, G. Clack, V. Jacobs, A. Marshall, M. Fennell, T. Green, J. M. Dixon
Journal: Journal of Clinical Oncology (2006)

13010 Background: Src kinase expression and activity is increased in many solid tumors including breast cancer, and Src kinase has a role in the regulation of cancer cell invasion. Thus, Src kinase is a potential therapeutic target. Targeting cancer cell invasion may be of particular value in early disease, although drug effects are unlikely to be measurable by conventional endpoints, for example tumor regression. This prospective study aimed to establish robust measures of Src activity in invasion-related pathways in tissue derived from EBC and to assess the variability between these measures, in order to establish a methodology for pharmacodynamic assessment of Src inhibition in clinical disease. Methods: Duplicate sets of core biopsies were taken from 30 patients, both at diagnosis and surgery. Biopsies were fixed immediately in either liquid nitrogen (luminometric analysis) or pre-cooled isopentane (IHC analysis). Formalin-fixed, paraffin-embedded tissue (FFPET) was also collected at the time of diagnosis. Levels of phospho-paxillin, phospho-focal adhesion kinase (FAK), total phosphotyrosine and total paxillin were measured in lysed tumor tissue using the Luminex system. Expression of activated Src, phospho-paxillin, phospho-FAK, total paxillin and total FAK was determined in sections of frozen tissue and FFPET, and assessed semi-quantitatively by visual examination. An analysis of variance (ANOVA) model was fitted to the Luminex data ( Table ). Results: All tumors expressed active Src, and there was a high level of expression, but low variability, of paxillin, FAK, phospho-paxillin and phospho-FAK. The subcellular localization of these markers could also be assessed in FFPET sections. Conclusion: The results indicate the feasibility of assessing the effect of a Src inhibitor on invasion-related endpoints in women awaiting surgery for EBC. [Table: see text] [Table: see text]
High Incidence of Cardiovascular Complications After CHOP-Like Chemotherapy In Lymphoma Patients From Poland – Retrospective Analysis of Polish Lymphoma Research Group (PLRG)
Authors: Wojciech Jurczak, Marcin Sobocinski, Jagoda Gorka, Jacek Cieslak, Joanna Drozd-Sokolowska, Piotr Boguradzki, Justyna Dzietczenia, Monika Joks, Andrzej Deptala, Magdalena Halasz, Tomasz Wrobel, Grzegorz Mazur, Aleksander Skotnicki
Journal: Blood (2010)
Enhanced Homing of HSPCs After Treatment with Prostaglandin E2 (PGE2) May Be An Effect of Transcriptional Regulation of CXC Chemokine Receptor 4 (CXCR4) Through Hypoxia Inducible Factor 1α (HIF1α)
Authors: Jennifer M Speth, Jonathan Hoggatt, Louis M. Pelus
Journal: Blood (2011)
3D printing of Mg-substituted wollastonite reinforcing diopside porous bioceramics with enhanced mechanical and biological performances
Authors: Dongshuang He, Chen Zhuang, Sanzhong Xu, Xiurong Ke, Xianyan Yang, Lei Zhang, Guojing Yang, Xiaoyi Chen, Xiaozhou Mou, An Liu, Zhongru Gou
Journal: Bioactive Materials (2016)

Mechanical strength and its long-term stability of bioceramic scaffolds is still a problem to treat the osteonecrosis of the femoral head. Considering the long-term stability of diopside (DIO) ceramic but poor mechanical strength, we developed the DIO-based porous bioceramic composites via dilute magnesium substituted wollastonite reinforcing and three-dimensional (3D) printing. The experimental results showed that the secondary phase (i.e. 10% magnesium substituting calcium silicate; CSM10) could readily improve the sintering property of the bioceramic composites (DIO/CSM10-x, x = 0-30) with increasing the CSM10 content from 0% to 30%, and the presence of the CSM10 also improved the biomimetic apatite mineralization ability in the pore struts of the scaffolds. Furthermore, the flexible strength (12.5-30 MPa) and compressive strength (14-37 MPa) of the 3D printed porous bioceramics remarkably increased with increasing CSM10 content, and the compressive strength of DIO/CSM10-30 showed a limited decay (from 37 MPa to 29 MPa) in the Tris buffer solution for a long time stage (8 weeks). These findings suggest that the new CSM10-reinforced diopside porous constructs possess excellent mechanical properties and can potentially be used to the clinic, especially for the treatment of osteonecrosis of the femoral head work as a bioceramic rod.
GW26-e1577 Serum Cystatin C as a Potential Predictor for the Progression of Prehypertension-to-hypertension
Authors: Ruimin Dong, Xing Shui, Xujing Xie, Zhenda Zheng, Suhua Li, Lin Chen, Jinlai Liu, Jieming Zhu
Journal: Journal of the American College of Cardiology (2015)
GW26-e5417 Mechanisms and factors governing periprocedural myocardial injury after coronary bifurcations stenting - Magnetic Resonance Late Gadolinium Enhancement Study
Authors: Aleksandra Michalek, Robert J. Gil, Dobrin Vassilev, Mariusz I. Furmanek, Monika Odyniec-Nowacka, Jaroslaw Rzezak, Tomasz Pawlowski, Phillip Tran, Hoang Quoc Bao, Jerzy Walecki
Journal: Journal of the American College of Cardiology (2015)
A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence
Authors: A Tefferi, H K Al-Ali, G Barosi, T Devos, H Gisslinger, Q Jiang, J-J Kiladjian, R Mesa, F Passamonti, V Ribrag, G Schiller, A M Vannucchi, D Zhou, D Reiser, J Zhong, R P Gale
Journal: Leukemia (2016)

Abstract RBC-transfusion dependence is common in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis. The objective of this study was to determine the rates of RBC-transfusion independence after therapy with pomalidomide vs placebo in persons with MPN-associated myelofibrosis and RBC-transfusion dependence. Two hundred and fifty-two subjects (intent-to-treat (ITT) population) including 229 subjects confirmed by central review (modified ITT population) were randomly assigned (2:1) to pomalidomide or placebo. Trialists and subjects were blinded to treatment allocation. Primary end point was proportion of subjects achieving RBC-transfusion independence within 6 months. One hundred and fifty-two subjects received pomalidomide and 77 placebo. Response rates were 16% (95% confidence interval (CI), 11, 23%) vs 16% (8, 26%; P =0.87). Response in the pomalidomide cohort was associated with ⩽4 U RBC/28 days (odds ratio (OR)=3.1; 0.9, 11.1), age ⩽65 (OR=2.3; 0.9, 5.5) and type of MPN-associated myelofibrosis (OR=2.6; 0.7, 9.5). Responses in the placebo cohort were associated with ⩽4 U RBC/28 days (OR=8.6; 0.9, 82.3), white blood cell at randomization &gt;25 × 10 9 /l (OR=4.9; 0.8, 28.9) and interval from diagnosis to randomization &gt;2 years (OR=4.9; 1.1, 21.9). Pomalidomide was associated with increased rates of oedema and neutropenia but these adverse effects were manageable. Pomalidomide and placebo had similar RBC-transfusion-independence response rates in persons with MPN-associated RBC-transfusion dependence.
Establishment of Trichimerism in the Dog Leukocyte Antigen (DLA)-Identical Canine Hematopoietic Transplant Model.
Authors: Scott S. Graves, William Hogan, George E. Georges, Christian Kuhr, Razvan Diaconescu, Michael Harkey, Eustacia Zellmer, Rainer Storb
Journal: Blood (2006)