tbuckley/cabot-search huggingface dataset:
Pathologic down-staging and complete pathologic response with gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder.
Authors: Sarah P. Psutka, Aria F. Olumi, Adam S. Feldman, Philip James Saylor, Donald S. Kaufman, Richard J. Lee
Journal: Journal of Clinical Oncology (2012)

307 Background: Neoadjuvant chemotherapy (NC) with MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) improves survival in muscle invasive urothelial cancer (MI−UC) with patients who achieve pathologic complete response (PCR) following radical cystectomy (RC). Gemcitabine/cisplatin (GC) NC is increasingly employed due to lower toxicity, however, its effectiveness as neoadjuvant therapy is controversial and multiple studies have reported poor utilization of this therapy, despite recent recommendations advocating for broader use. We describe pathologic and clinical outcomes following NC and RC. Methods: We retrospectively evaluated patients with MI−UC who received NC between 2003 and 2011 (n=38). Those who were treated with neoadjuvant radiation therapy (n= 15) were excluded. We compared initial clinical stage at surgery to final pathological stage and assessed overall−median progression free−survival. Mean follow−up was 25 months (SD 21.6, range 3 –76 months). Results: Twenty-three patients who received NC were included. Nineteen patients (82.6%) were treated with GC, 3 (13.0%) with MVAC, and 1 (4.3%) with gemcitabine/paclitaxel. The median time from start of NC to RC was 119 days (IQR 98.5−146). 10/19 (52.6%) patients treated with GC achieved PCR (pT0) from clinical stage T2 (n=5), cT3 (n=2) and cT4 (n=3), and 6 (31.2%) were downstaged to pT1 and pTIS from cT2. Two patients treated with MVAC were downstaged to pT1 and one achieved PCR. Median recurrence-free survival was 13 months (IQR 6−19 months) with 8 patients developing recurrent or metastatic UC following RC. At median follow-up of 19 months (IQR 8−31.2 months, Range 1−71 months), 15/23 (65.2%) patients were disease free, all of whom had received GC NC prior to cystectomy. Conclusions: Neoadjuvant GC for MI−UC was associated with a 52.6% PCR rate at RC and was well tolerated. These data compare favorably with published data on GC and MVAC as NC, and warrant further study.
Deficient Ribosomal Protein S19 in Diamond-Blackfan Anemia Causes a Reduction in bcl-2 and Bad and Leads to Apoptosis in Erythroid Progenitor Cells.
Authors: Koichi Miyake, Taiju Utsugisawa, Johan Flygare, Thomas Kiefer, Isao Hamaguchi, Johan Richter, Stefan Karlsson
Journal: Blood (2005)
The Addition of Bevacizumab (B) to Lenalidomide and Low Dose Dexamethasone Does Not Significantly Increase Response in Relapsed or Refractory Multiple Myeloma (NCI#7317).
Authors: Natalie Scott Callander, Stephanie Markovina, Mark B. Juckett, Elizabeth Wagner, Jill Kolesar, Walter Longo, Eliot C. Williams, Kyungmann Kim, Jae Werndli, Shigeki Miyamoto
Journal: Blood (2009)
Liver transplantation in patients with primary antibody deficiency
Authors: Silje F. Jørgensen, Magnhild E. Macpherson, Kristian Bjøro, Tom H. Karlsen, Henrik M. Reims, Krzysztof Grzyb, Bjarte Fosby, Børre Fevang, Pål Aukrust, Ingvild Nordøy
Journal: Journal of Allergy and Clinical Immunology (2016)
A Prospective Evaluation of Bleeding Tendency and Efficacy of Antihemorrhagic Treatments in Patients with Increased Von Willebrand Factor (VWF) Clearance (Von Willebrand Disease Vicenza AND C1130F Mutation).
Authors: Giancarlo Castaman, Alberto Tosetto, Augusto B. Federici, Francesco Rodeghiero
Journal: Blood (2008)
Predictors of long-term survival in patients with metastatic renal cell carcinoma in the cytokine era: An analysis of 473 patients treated between 1995 and 2005.
Authors: N. Shinohara, S. Maruyama, T. Abe, A. Sazawa, K. Nonomura
Journal: Journal of Clinical Oncology (2011)

335 Background: Based on the clinical data in Japanese renal cell carcinoma (RCC) patients who underwent cytokine therapy (Naito et al, Eur Urol 2010), the overall survival (OS) of these patients has been considered to be better than that of Caucasian patients. We identified long-term survivors among a cohort of 473 metastatic RCC patients, and explored clinical predictors of OS in these patients. Methods: Between 1995 and 2005, 473 patients with metastatic RCC were the subjects of this retrospective analysis. Three hundred sixty-one (76%) patients received IFN-α and no patient did molecular-targeted drugs. The patients with survival times of greater than 5 years after the development of metastases were identified as long-term survivors. Multiple logistic regression analysis was performed to evaluate the impact of clinical variables potentially influencing OS. Results: Median OS for all patients was 22.3 months (95%CI 18.7-27.6), the estimated 5-year survival rate was 27.4% (95% CI 22.9-31.9). Sixty-eight patients (14.4%) among 473 patients were identified as long-term survivors. Twenty-six (38%) had metastases at diagnosis of kidney cancer, 3 (4%) and 11 (16%) had liver mets and bone mets, respectively. According to MSKCC risk classification, 19 (28%), 28 (41%), and 6 (9%) were classified as favorable, intermediate, and poor risk, respectively. All patients had undergone prior nephrectomy, and 40 (59%) underwent metastatectomy. Multiple logistic regression analysis from all patients identified metastatectomy (HR 5.0; 95%CI 2.7-9.5) and MSKCC risk group (HR 3.7; 95%CI 1.5-9.1) as adverse prognostic factors for long-term OS. Conclusions: Selected patients with metastatic RCC who can undergo metastatectomy have a good opportunity for long-term survival, especially those with favorable or intermediate risk classified by MSKCC risk classification. No significant financial relationships to disclose.
Adjuvant surgery in patients with testicular cancer undergoing post-chemotherapy retroperitoneal lymph node dissection.
Authors: Hooman Djaladat, Craig R. Nichols, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2012)

335 Background: Up to 50% of patients who undergo induction chemotherapy for metastatic germ cell cancer have significant residual retroperitoneal disease in whom post chemotherapy RPLND is indicated with intent to cure. Since complete resection is a critical component in PC-RPLND, meticulous dissection of the retroperitoneum with resection of involved organs or structures (adjuvant surgery) should be considered whenever feasible to ensure optimal outcome. Methods: From 2004 to 2010, 85 testicular cancer patients underwent PC-RPLND by a single surgeon (SD). A bilateral template approach was utilized with nerve sparing technique whenever feasible. The clinico-pathologic and outcome of patients who underwent adjuvant surgery during PC-RPLND were reviewed. Results: Of 85 patients undergoing PC-RPLND, 28 (33%) required adjuvant procedures. Thirteen (15%) required vascular procedures including cavotomy/ caval resection in six, aortic resection in eight, common iliac vessels resection in four and renal vessels resection/reimplant in two. Twelve patients (14%) required adjuvant nephrectomy (10/12 left sided). There was 1 ureteral resection with appendiceal substitution, 1 partial duodenectomy, 2 cholecystectomy, 2 thoracotomies, 4 liver resection/ biopsy, and 1 neck dissection. There were 8 early complications (28%) including vocal cord paralysis, brachial plexus injury, lower extremities compartment syndrome, thigh numbness, UGI bleeding, retroperitoneal hematoma and alcohol withdrawal. No peri-operative death was reported. Retroperitoneal pathology revealed mature teratoma in 11 (39%), fibrosis in 8 (28%) and viable germ cell tumor (GCT) in 9 (32%) patients. 75%, 82% and 66% of patients with fibrosis, teratoma and viable GCT had no evidence of recurrence in mean follow up of 18 months. Conclusions: A significant number of patients undergoing PC-RPLND require adjuvant surgery including vascular procedures and nephrectomy. The excellent outcomes associated with low operative morbidity/mortality validate such aggressive surgical approaches performed by experienced surgeons.
The economic and clinical costs of chronic kidney disease following radical and partial nephrectomy in the management of small renal masses.
Authors: S. L. Chang, L. E. Cipriano, L. C. Harshman, B. I. Chung
Journal: Journal of Clinical Oncology (2011)

353 Background: Postoperative chronic kidney disease (PCKD), defined as a glomerular filtration rate of &lt; 60mL/min/1.73m 2 , is a recognized adverse outcome after extirpative therapy for small renal masses (SRM, ≤ 4cm). We quantified the long-term economic and clinical costs of PCKD following radical and partial nephrectomy for the management of SRM. Methods: Using a Markov model, we evaluated open and laparoscopic approaches for radical and partial nephrectomy in the treatment of SRMs. The base case was a 65-year old healthy individual with a unilateral SRM and normal renal function. We used a 3-month cycle length, lifetime horizon, societal perspective, and 3% discount rate. The costs, quality of life adjustments, and transition probabilities were estimated from the literature, Medicare, and expert opinion. Health outcomes were measured in quality-adjusted life-years (QALY) gained and costs in 2008 U.S. dollars. The model was tested with sensitivity analyses. Results: The average discounted lifetime outcomes are listed in the Table. There were minimal differences between the open and laparoscopic approaches. PCKD led to a substantial increase costs and decrease in health outcomes. The impact of PCKD was indirectly associated with age. Conclusions: Partial nephrectomy provides cost-savings and improved health outcomes compared to radical nephrectomy in the management of patients with SRMs. Both procedures incur significant economic and clinical costs due to the development of PCKD. A discussion about the potential for PCKD should be incorporated into the informed consent for surgical treatment of SRMs. [Table: see text] No significant financial relationships to disclose.
Effect of IGF1R protein expression on benefit to adjuvant trastuzumab in early-stage HER2+ breast cancer in NCCTG N9831 trial.
Authors: M. M. Reinholz, A. C. Dueck, B. Chen, X. Geiger, A. E. McCullough, R. B. Jenkins, W. L. Lingle, C. Andorfer, N. E. Davidson, S. Martino, P. A. Kaufman, L. A. Kutteh, G. W. Sledge, L. Harris, J. Gralow, E. A. Perez
Journal: Journal of Clinical Oncology (2011)

10503 Background: Preclinical evidence suggests that increased IGF1R (insulin-like growth factor receptor) signaling interferes with trastuzumab action, suggesting a possible mechanism of resistance. Thus, we evaluated IGF1R prevalence, relationship with demographic data, and association with disease-free survival (DFS) of patients (pts) randomized to chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the prospective phase III HER2+ adjuvant N9831 trial. Methods: The % of cells with IGF1R staining at 0 (none), 1+ (weak), 2+ (moderate), and 3+ (strong) intensity was determined in TMA sections containing 3 cores per block (N=1210) or whole tissue sections (WS) (N=536) using IHC (Cell Signaling 1:200). A tumor was considered positive (IGF1R+) if any core or WS had ≥1+ membrane staining in >0% invasive tumor cells. Median follow-up was 6.1 yrs. Other cutpoints of positivity, including ≥2+ and 3+ membrane staining in >0% invasive tumor cells were also examined. Results: Of 1,746 pts, 708 (41%) were IGF1R+. IGF1R+ was associated with lower age (median 48 vs 51, t-test p=0.006), higher % ER/PgR positivity (78% vs 35%, chi sq p<0.001), nodal positivity (89% vs 83%, chi sq p<0.001), tumors ≥2 cm (72% vs 67%, chi sq p=0.02), lower % high grade (66% vs 76%, chi sq p<0.001) but not associated with race or tumor type. IGF1R did not impact DFS within arms. The impact of IGF1R on DFS between Arms A and B or C is shown in the table below. Conclusions: In contrast to preclinical studies that suggest a decrease in trastuzumab sensitivity in IGF1R+ tumors, our data show benefit of adjuvant trastuzumab for both IGF1R+ and IGF1R- groups (with slightly greater benefit in the IGF1R+ group) independent of cutpoint. Supported by NIH CA129949, CA25224, CA114740 and the BCRF. IGF1R Arm N Events HR 95% CI P value 5-yr DFS + AB 223277 6265 0.77 0.54-1.10 0.15 75.979.9 - AB 357354 10477 0.74 0.55-1.00 0.05 72.180.1 + AC 223208 6229 0.48 0.31-0.75 0.001 75.988.9 - AC 357327 10465 0.66 0.48-0.90 0.009 72.183.2 + BC 277208 6529 0.57 0.37-0.90 0.02 79.988.9 - BC 354327 7765 0.92 0.66-1.28 0.62 80.183.2 Interaction with IGF1R p values: A vs B 0.76; A vs C 0.28; B vs C 0.14.
<i>Notes from the Field</i>: Plague in Domestic Cats — Idaho, 2016
Authors: Ahmed M. Kassem, Leslie Tengelsen, Brandon Atkins, Kimberly Link, Mike Taylor, Erin Peterson, Ashley Machado, Kris Carter, Scott Hutton, Kathryn Turner, Christine Hahn
Journal: MMWR Morbidity and Mortality Weekly Report (2016)
Cytogenetics in Pediatric MDS - Data of the EWOG-MDS 98 Study.
Authors: K. Michalova, H. B. Beverloo, G. Michaelsen, B. Schlegelberger, J. Harbott, O. A. Haas, G. B. Kerndrup, L. Sainati, E. Bergstraesser, H. Hasle, J. Starý, M. Trebo, M. M. Van den Heuvel-Eibrink, M. Zecca, P. Noellke, A. Fischer, C. M. Niemeyer, D. R. Betts
Journal: Blood (2005)
The Eukaryotic Translation Initiation Factor 4E (eIF4E) Has Oncogenic Functions and May Represent a New Therapeutic Target In Diffuse Large B Cell Lymphoma (DLBCL)
Authors: Biljana Culjkovic, Tharu Fernando, ShaoNing Yang, Ari M. Melnick, Katherine LB Borden, Leandro Cerchietti
Journal: Blood (2013)
Induction of Apoptosis and Cell Cycle Arrest in Acute Myeloid Leukemia Cells by Histone Deacetylase Inhibitor, Suberoyl Hydroxamic Acid (SAHA): Lack of Cross-Resistance to Cytosine Arabinoside and Etoposide.
Authors: Sabine Dreyer, Thomas Decker, Michaela Wagner, Christian Peschel, Thomas Licht
Journal: Blood (2004)
An analysis of arterial hypertension and mutational status as predictive factors for results of sunitinib (SU) therapy in gastrointestinal stromal tumors (GIST).
Authors: P. Rutkowski, E. Bylina, T. Switaj, A. Klimczak, S. Falkowski, J. Kroc, I. A. Lugowska, M. Brzeskwiniewicz, A. Wozniak, J. Siedlecki, J. Limon
Journal: Journal of Clinical Oncology (2011)

10017 Background: The purpose of the study was to analyze the outcomes of treatment and factors predicting effects of SU therapy in inoperable/metastatic GIST CD 117(+) patients after failure on imatinib therapy. Mutational status is well-known factor related to the results of therapy with tyrosine kinase inhibitors. Arterial hypertension is common adverse event during SU treatment but it was also reported as predictive factor for results of SU treatment of renal-cell carcinoma patients—this last phenomenon has not been analyzed in GIST patients. Methods: We identified 107 consecutive patients with advanced GIST in all but one cases after progression on imatinib treated in one center (35 were included in the trial A6181036) with SU (2nd line) at initial dose 50 mg daily 4 weeks on/2 weeks off. Median follow-up time was 23 months. Results: The estimated median progression-free survival (PFS; calculated form the date of the start of SU) was 44 weeks and 1-year PFS rate—42%. The estimated overall survival (calculated both from start of SU and IM) was 73 weeks and 51 months, respectively. We identified two independent factors significantly influenced PFS and OS in univariate and multivariate analysis, respectively: tumor genotype (p=0.04; hazard ratio [HR]=1.22) and presence of arterial hypertension (p=0.0007; HR=3.2; HA defined as occurrence of systolic blood pressure >140 and diastolic pressure >90 mm Hg; or deterioration of preexisting HA). 1-year PFS was 65% (median: 74 weeks) in 53 patients with HA vs. 22% (median: 17.2 weeks) in 54 patients without HA. Patients with primary tumors carrying mutations in KIT exon 9 and wild-type tumors had substantially better 1-year PFS (68% and 57%; median 65 and 50.4 weeks respectively) than patients with tumors with exon 11 KIT or PDGFRA mutants (33% and 17%; median 31.1 and 9.7 weeks, respectively). Conclusions: We confirmed that many advanced GIST patients benefit from sunitinib therapy with overall survival exceeding 1.5 year. Primary tumor genotype and SU-induced arterial hypertension (as surrogate of its antiangiogenic activity) are two independent factors influencing the progression-free survival.
Dose to regions within the prostate during the learning curve phase in low dose rate (LDR) brachytherapy: Sector analysis of 71 consecutive patients at Princess Margaret Hospital.
Authors: E. P. Saibishkumar, D. Iupati, J. Borg, K. Fernandes
Journal: Journal of Clinical Oncology (2011)

91 Background: It is important to evaluate the dose distribution within the prostate in highly conformal and operator dependent treatment like brachytherapy, especially in the learning curve phase when technical skill is evolving. We report detailed dosimetric analysis of prostate sectors in the initial 71 consecutive implants performed by a physician in the first year of practice. Methods: Implants were done based on a pre plan but intra-operative adjustments were made to account for actual seed positions and addition of seeds and the final dose distribution to the prostate was documented as Intra-operative (IO) plan. Post-implant assessment was at 1 month using fused MRI/CT scans. Twelve prostate sectors were generated by division into 4 quadrants (anterior, posterior, laterals) and 3 segments (base, middle and apex). IO and post-implant (PI) V100 and D90 for sectors and whole prostate were recorded. Comparative (Wilcoxon Rank Sum) and association (Spearman's rank correlation) testing was performed for univariate analysis. Optimal dosimetry values for the entire prostate and sectors were defined as D90 &gt;90% and V100 &gt;85%. Results: Seventy implants were optimal (out of 71) with mean prostate PI V100 and D90 of 95.5% and 117.1%. Only 1 sector had suboptimal mean PI V100 and D90 (70.3% and 85.9%), significantly lower than IO (p&lt;0.001), contributing to lower PI V100 for the base (88%) and anterior sectors (86.9%). The mean IO D90 of apical sectors (126%) was lower than base and mid gland (131% and 132% respectively) and lateral sectors was (134%) higher than anterior and posterior sectors (123% and 126%) consistent with a modified peripheral loading approach. D90 decreased from IO to PI plan in anterior (123% vs 106%, p&lt;0.001) and base sectors (132% vs 108%, p&lt;0.001) while increase was noted in apical (126% vs 133%, p&lt;0.001) and posterior sectors (126% vs 131%, p=0.006). Conclusions: Results are encouraging with optimal dosimetry in 11/12 sectors in most patients, and sector analysis provided insight into planning factors and provided useful data for refinement in practice. Further study correlating sector analysis with clinical outcomes is required. No significant financial relationships to disclose.
AMC-053: Pilot Study of an Oncolytic Viral Strategy Using Bortezomib with ICE +/- Rituximab for Relapsed/Refractory HIV+ Lymphomas
Authors: Erin Gourley Reid, David Looney, Frank Maldarelli, Ariela Noy, David H. Henry, David M. Aboulafia, Juan Carlos Ramos, Joseph Sparano, Richard F. Ambinder, Jeannette Lee, Ronald T. Mitsuyasu, William Wachsman
Journal: Blood (2016)
Abstract P095: An Expression-Based in Vivo Protein Trap Screen Enriches Cardiac Mutants and Reveals Cardiac Functions of Methionine Adenosyltransferase 2A in Zebrafish
Authors: Yonghe Ding, Wei Huang, Yun Deng, Beninio Jomok, Alissa Caron, Jingchun Yang, Xueying Lin, Stephen Ekker, Xiaolei Xu
Journal: Circulation Research (2011)

The present forward mutagenesis screen strategies in vertebrates are difficult to identify genes and mutants affecting a specific organ of interest. Here, we report a strategy to enrich cardiac mutants by leveraging the transparency of zebrafish embryos and the high efficiency of pGBT-RP2 (RP2), a gene-breaking transposon-based in vivo protein trap cassette. By selectively raising up founder fish with Red Fluorescence Protein (RFP) reporter expression in the heart, we successfully generated 15 cardiac mutant lines. All tagged loci exhibit cardiac expression and the overall knockdown efficiency at transcript level is greater than 95%. One of the cardiac lines, RP2_ #135, is a homozygous embryonic lethal line that is caused by a RP2 insertion in methionine adenosyltransferase 2a (mat2a) . Taking advantage of the LoxP sites inside the RP2 vector, we further demonstrated that the cardiac phenotypes in RP2_ #135 is due to a disrupted expression of mat2a in cardiomyocytes, as indicated by a conditional rescue assay using Tg(cmlc2:Cre-YFP) , a myocardium specific Cre transgenic line. Finally, we show that the reduced cardiomyocyte number, but not size, in the mat2a mutant is conveyed by the p53-mediated apoptosis pathway. Together, our data prove the feasibility of a facile approach to generate a vertebrate cardiac mutant collection with the following two unique features. First, the expression dynamics of each tagged gene is reported by RFP. Second, the causality between the tissue-specific gene expression and the resulted cardiac phenotypes can be attested genetically.
A novel combined radiologic method for evaluation of the response to chemotherapy for primary bone sarcoma.
Authors: S. Miwa, T. Shirai, J. Taki, N. Yamamoto, H. Nishida, K. Hayashi, H. Kimura, A. Takeuchi, K. Igarashi, H. Tsuchiya
Journal: Journal of Clinical Oncology (2011)

10035 Background: In the treatment of primary bone sarcoma, evaluation of chemotherapeutic effects is extremely important. In this study, we compared radiological evaluations and histological response, and developed a combined radiological evaluation method for assessing the response to chemotherapy. Methods: A total of 79 patients with primary bone sarcomas were examined by X-ray photography (Xp), angiography, magnetic resonance imaging (MRI), 201Tl scintigraphy (Tl) and 99mTc-MIBI scintigraphy (MIBI) to evaluate their response to preoperative chemotherapy. Patients were classified as responders and non-responders according to radiological images: sclerotic changes and cortical recovery in Xp; vascular changes in angiograms; reduction rate of extraskeletal mass in MRI; and percentage reduction in Tl and MIBI. The sensitivity, specificity, accuracy, and kappa values in radiological evaluation were calculated. All resected tumors were evaluated histologically and classified as a good response (≥ 90% necrosis) or a poor response (≤ 90% necrosis). Finally, we developed a combined radiological scoring system according to the predictive power of the images. Results: Sensitivity, specificity, and accuracy were 90.9%, 38.2%, and 67.5% (K=0.31), respectively, for Xp; 91.7%, 33.3%, and 66.7% (K=0.27) for angiography; 81.0%, 67.6%, and 75.0% (K=0.49) for MRI; 78.9%, 72.4%, and 76.1% (K=0.51) for Tl; and 85.3%, 69.2%, and 78.3% (K=0.55) for MIBI. Our combined radiological scoring method gave values of 93.3%, 76.5%, and 86.1% (K=0.71), which was the highest accuracy (86.1%) and kappa value (0.71). Conclusions: Our combined radiological scoring system showed high correlation with histological response for assessing the effects of preoperative chemotherapy for primary bone sarcoma.
TCR-Ligand Dissociation-Rate, a Reliable and Determining Parameter, Identifying Tumor-Reactive CD8 T Cells of High Avidity and Functional Potency
Authors: Nathalie Rufer, Mathilde Allard, Barbara Couturaud, Laura Carretero, Julien Schmidt, Minh Ngoc Duong, Petra Baumgaertner, Philippe Gannon, Daniel Speiser, Michael Hebeisen
Journal: Blood (2016)
Combination of a Novel Proteasome Inhibitor NPI-0052 and Lenalidomide Trigger in Vivo Synergistic Cytotoxicity in Multiple Myeloma
Authors: Dharminder Chauhan, Ajita V. Singh, Mohan Brahmandam, Giada Bianchi, Klaus Podar, Teru Hideshima, Nikhil Munshi, Paul Richardson, Michael A. Palladino, Kenneth C. Anderson
Journal: Blood (2008)