tbuckley/cabot-search huggingface dataset:
Multi-institutional review of sequential intravesical gemcitabine and mitomycin C chemotherapy for non-muscle-invasive bladder cancer.
Authors: Andrew J. Lightfoot, Benjamin N. Breyer, Henry M. Rosevear, Badrinath Konety, Michael A. O'Donnell
Journal: Journal of Clinical Oncology (2012)

294 Background: Combination chemotherapy is the standard of care for neoadjuvant, adjuvant, and metastatic bladder cancer due to increased efficacy when compared to monotherapy. We report our experience with sequential intravesical combination chemotherapy using gemcitabine and mitomycin C (MMC) for non-muscle invasive bladder cancer (NMIBC). Methods: We performed a multi-institutional retrospective review of 47 consecutive patients who received 6 weekly treatments with sequential gemcitabine (1g) and mitomycin C (40mg) chemotherapy for NMIBC. Thirty patients received treatment at University of Iowa, 14 at UCSF and 3 at University of Minnesota. Results: A total 47 patients (median age 70, range 32-85; 36 males, 11 females) previously failing a median of 2 intravesical treatments were reviewed. The complete response (CR), 1-year recurrence-free survival (1-RFS) and 2-year recurrence-free survival (2-RFS) for all patients was 68%, 48% and 38%, respectively. In all, 14 of 47 patients (30%) remain free of recurrence with a median time to followup of 26 months (range 6-80 months). The median time to recurrence for all patients who recurred was 4 months (range 1-33 months). Ten patients required cystectomy. Conclusions: Sequential intravesical combination chemotherapy using gemcitabine and MMC appears to be a useful treatment for patients with a history of NMIC which has failed BCG or other intravesical therapy, in addition to patients with intermediate and high-risk disease.
Consolidation Radiotherapy Improved Survival in Limited Stage Diffuse Large B-Cell Lymphoma (DLBCL): A Nationwide Multi-Institutional Registry of 816 Cases in Thailand
Authors: Lalita Norasetthada, Weerasak Nawarawong, Arnuparp Lekhakula, Jakrawadee Julamanee, Chittima Sirijerachai, Kanchana Chansung, Kitsada Wudhikarn, Udomsak Bunworasate, Noppadol Siritanaratanakul, Archrob Khuhapinant, Tontanai Numbenjapon, Kannadit Prayongratana, Tawatchai Suwanban, Suporn Chuncharunee, Pimjai Niparuck, Somchai Wongkhantee, Peerapon Wong, Nisa Makruasi, Nonglak Kanitsap, Tanin Intragumtornchai
Journal: Blood (2015)
Associations of Specific Postoperative Complications With Outcomes After Elective Colon Resection
Authors: John E. Scarborough, Jessica Schumacher, K. Craig Kent, Charles P. Heise, Caprice C. Greenberg
Journal: JAMA Surgery (2016)

Numerous quality initiatives have been implemented in an effort to minimize the onus of postoperative complications on clinical and economic outcomes after major surgery. It is unknown which complications have the greatest overall effect on these outcomes.To quantify the associations of specific postoperative complications with outcomes after elective colon resection.Patients undergoing elective colon resection between January 1, 2012, and December 31, 2013, who were included in the Colectomy-Targeted American College of Surgeons National Surgical Quality Improvement Program were assessed for the development of specific types of postoperative complications. The overall contributions of these complications to subsequent clinical and resource use outcomes were assessed.The main outcomes were 30-day mortality, end-organ dysfunction, reoperation, prolonged hospitalization, nonroutine discharge status, and hospital readmission. Risk-adjusted population attributable fractions were estimated for each complication-outcome pair. The population attributable fractions for a specific complication represented the percentage reduction in a given outcome that would be expected if exposure to that complication was completely eliminated.A total of 26 682 patients undergoing elective colon resection were included for analysis; 13 870 patients were women (52.0%) and 15 088 (56.5%) were younger than 65 years. The most common index complications were ileus (n = 3140; 11.8%), bleeding (n = 2032; 7.6%), and incisional surgical site infection (n = 1873; 7.0%). Anastomotic leak was associated with the incidence of end-organ dysfunction, mortality, reoperation, and hospital readmission, with estimated population attributable fractions of 33.3% (95% CI, 29.6-36.8), 20.0% (95% CI, 14.0-25.7), 48.4% (95% CI, 45.7-51.0), and 20.6% (95% CI, 19.1-22.1) for each of these respective outcomes. The effect of complications, such as urinary tract infection, venous thromboembolism, and myocardial infarction, on these outcomes was comparatively small.Anastomotic leak has a large overall effect on 30-day clinical and economic outcomes after elective colon resection. The findings of our study support the adoption of a procedure-targeted approach to surgical quality improvement and describe a practical method for assessing complication effect.
Long Noncoding RNA Meg3 Controls Endothelial Cell Aging and Function
Authors: Reinier A. Boon, Patrick Hofmann, Katharina M. Michalik, Noelia Lozano-Vidal, Denise Berghäuser, Ariane Fischer, Andrea Knau, Nicolas Jaé, Christoph Schürmann, Stefanie Dimmeler
Journal: Journal of the American College of Cardiology (2016)
A multicenter, open-label phase II trial of dovitinib, a fibroblast growth factor receptor 1 (FGFR1) inhibitor, in <i>FGFR1-</i>amplified and nonamplified metastatic breast cancer (BC).
Authors: F. Andre, T. D. Bachelot, M. Campone, F. Dalenc, J. M. Perez-Garcia, S. A. Hurvitz, N. C. Turner, H. S. Rugo, J. Baselga, Y. Zhang
Journal: Journal of Clinical Oncology (2011)

289 Background: Amplification of the FGFR1 gene occurs in ≈ 10% of BC, correlates with FGFR1 overexpression, and is mainly observed in estrogen receptor (ER)-positive human epidermal growth factor receptor 2 (HER2)- BCs. Dovitinib (TKI258) is a multitargeted tyrosine kinase inhibitor that demonstrated potent antitumor activities in FGFR1-amplified tumor cell lines. This phase 2 study evaluated the efficacy and safety of dovitinib in metastatic HER2- BC. Methods: Patients were stratified into 4 groups based on FGFR1 and hormone receptor (HR) tumor subtype: 1) FGFR1+, HR+; 2) FGFR1+, HR-; 3) FGFR1-, HR+; 4) FGFR1-, HR-. Screening for FGFR1 status was performed by fluorescence/chromogenic in situ hybridization (cutoff ≥ 6 gene copies). Dovitinib (500 mg) was administered once daily on a 5-day-on/ 2-day-off schedule. The primary endpoint was RECIST best overall response rate in patients with measurable disease per external radiology review. Results: Data from 77 of 81 treated patients were available as of January 2011 (n=21, n=34, n=22 in groups 1, 3, 4, respectively). Median number of prior therapies in the metastatic setting was 2 chemotherapy lines (all patients) and 2 endocrine therapy lines (HR+ patients). Liver metastases were present in 58% of patients (81%, 50%, 50% in groups 1, 3, 4, respectively). Most common adverse events included vomiting (75%; grade 3 [g3]: 6%), diarrhea (72%; g3: 6%), nausea (62%; g3: 5%), and asthenia (61%; g3: 17%). Median dovitinib exposure was 1.7 (range, 0-8.2) months, including 8 patients with &gt; 4 months of therapy. Of patients with measurable disease at baseline, in group 1, 13% had unconfirmed partial responses and 44% had stable disease ≥ 4 months (SD4). In groups 3 and 4, 29% and 11% had SD4. Conclusions: This is the first trial reporting efficacy of an FGFR1 inhibitor in patients with FGFR1-amplified BC. Dovitinib showed antitumor activity in patients with HR+, FGFR1- amplified BC and disease stabilization in other subgroups. FGFR1 is likely a relevant target in BC, and FGFR1 amplification may define a segment of dovitinib-sensitive disease. Further evaluation of dovitinib in patients with HR+ BC is planned.
Prognostic factors for response to systemic treatments carried out in patients with advanced renal carcinoma.
Authors: C. Muriel, E. Esteban, P. Martinez-Camblor, A. Astudillo, G. Crespo, P. Pardo, M. Izquierdo, J. Berros, E. Gutierrez, A. J. Lacave
Journal: Journal of Clinical Oncology (2011)

369 Background: The analysis of predictive factors of response could help to select those patients with advanced renal cell carcinoma (RCC) who would be good candidates for systemic treatments Methods: The expression of several biomarkers was retrospectively analysed by immunohistochemistry (IHC), as well as 2 analytical variables: thrombocytosis and neutrophilia, in 135 patients with advanced RCC treated with cytokines (CK) and/or biological agents and was correlated to the response. Results: 67 patients were treated only with biological agents and 68 with CK (23 treated also with biological agents). Univariate statistical analysis: HIF-1alpha did not correlate significantly with the response to these drugs. The overexpression of ACIX was associated to a larger response (%) to biological agents such as sunitinib (65.9 vs. 16.7 p&lt;0.001) or sorafenib (61.9 vs 0 p=0.007), and CK (22.6 vs. 0 p=0.038). PTEN showed a predictive value for response (%) to sunitinib (70.8 vs. 34.1 with PTEN negative p=0.005). p21 was associated to a lower response (%) with sunitinib (35.9 vs. 65.4 with p=0.025). Thrombocytosis was not significantly associated with the response (%) to biological agents, although it was associated to CK (0 vs. 20 without thrombocytosis p=0.017). Neutrophilia correlated with a smaller response to biological agents (29.6 vs. 57.5 without neutrophilia, p=0.045), although it did not associate with a response to CK. In the multivariate analysis, overexpression of ACIX was an independent predictor of a larger response to biological agents and CK with an OR of 8,773 (p&lt;0.001). Conclusions: Our findings prove the usefulness of ACIX to select patients with advanced RCC candidates to receive systemic treatment. PTEN and p21 could be important in the prediction of response to sunitinib. Thrombocytosis and neutrophilia appear to relate to the response to CK and biological agents respectively. No significant financial relationships to disclose.
Loss of B-cell translocation gene 2 in estrogen receptor–positive breast cancer and tamoxifen resistance.
Authors: T. Hayashida, H. Jinno, M. Takahashi, Y. Kitagawa
Journal: Journal of Clinical Oncology (2011)

63 Background: The expression analysis in ER positive human breast cancer already demonstrated the loss of nuclear expression of BTG2, the cell cycle regulator, in 46% of tumors and showed a significant inverse correlation with cyclinD1 expression. Our analysis of Oncomine database suggested that BTG2 expression might be related to the clinical outcome in patients with tamoxifen treatment. Methods: The examinations to evaluate whether BTG2 expression affects the sensitivity against tamoxifen were conducted both in vitro and in vivo. Results: In vitro cellular proliferation assay using tamoxifen against ER positive cell lines revealed that T47D expressing high level of endogenous BTG2 showed more drug sensitivity than MCF7 expressing low level of BTG2. (MCF7; IC50=4.48uM, T47D; =1.31uM) Tetracycline-inducible BTG2 expression model was developed in MCF7 and the cellular proliferation was strongly inhibited by the concomitant administration of tetracyclin and tamoxifen in vitro. Then, the cell line was injected into the mammary fat pad of immunodeficient mice. After the tumors grew more than 125mm 3 , these tumor bearing mice were administered the water including tetracyclin and/or tamoxifen pellet for 3 weeks. Tumor growth ratio was significantly suppressed in the concomitant administration of tetracyclin and tamoxifen in comparison with the animal treated with single agent. (p=0.044) Consistently, tumor weight and Ki67 expression were also significantly suppressed in the mice administered both tamoxifen and tetracyclin. (BW; p=0.034, Ki67; p=0.039) The cohort of 60 patients treated with adjuvant tamoxifen monotherapy was available online. Comparison of disease-free survival (DFS) of patients with positive BTG2 expression versus patients with loss of BTG2 expression revealed an univariate association in the dataset (log-rank probability, p=0.029). Multivariate analysis indicated that BTG2 expression resulted an independent prognostic factor for DFS (HR, 0.69; 95% CI, 0.495 to 0.963; p=0.029). Conclusions: Despite further validation studies need to be conducted, BTG2 expression may be useful biomarker to identify patients appropriate for tamoxifen treatment.
Curette lavage fluid analysis of EGFR, KRAS, and P53 mutations in lung cancer patients
Authors: Fumihiro Yamaguchi, Kunihiko Fukuchi, Sakiko Tazawa, Hidethugu Tateno, Eisuke Kato, Aya Wakabayashi, Asami Tada, Takuya Iwasaki, Makoto Hayashi, Yutaka Thuchiya, Jun Yamashita, Norikazu Takeda, Shogo Tomita, Fumio Kokubu
Journal: European Respiratory Journal (2011)

Purpose:  Mutation analyses of individual lung cancer patients should provide useful information for determining treatment. When sufficient tissue samples for pathology cannot be collected by bronchoscopy, cytology is substituted to establish diagnosis. In this study, epidermal growth factor receptor ( EGFR ),  KRAS , and  P53  mutations in cells attached to the curette were analyzed by collecting the lavage fluid.   Subjects:  Samples were obtained from 63 lung cancer patients receiving treatment from April, 2009 to October 2010 at the Department of Respiratory Medicine, Showa University Fujigaoka Hospital. Official approval for the study was obtained in advance from the Ethics Committee for Genomic Research at Showa University.   Methods:  DNAs were extracted from cells in the curette lavage fluid. PCRs were performed to amplify mutation hot spot regions in  EGFR ,  KRAS , and  P53 . The PCR products were direct-sequenced, and the mutations confirmed by sequencing with both forward and reverse primers.   Results and discussion:  Seven patients were found with  EGFR  mutations and seven with  P53  mutations. No mutation in  KRAS  was identified. The mutation rates observed here for the three genes were lower than those reported previously by others. However,  EGFR  exon 19 deletions were identified in 6 of 53 non-small cell lung cancer patients in this study (11.3%), making it comparable to that reported elsewhere. It is felt that in instances where the number of cancer cells in the test sample is low, it becomes difficult to detect point mutations and insertions. It should be cautioned that in instances where direct sequencing is utilized, mutation detection standards may vary according to the individual facility.
Use of DARPP-32 to increase interactions between EGFR and ERBB3 and to promote gastric cancer resistance to gefitinib.
Authors: Shoumin Zhu, Abbes Belkhiri, Alexander Zaika, Wael El-Rifai
Journal: Journal of Clinical Oncology (2012)

18 Background: Dopamine and cAMP-regulated phosphoprotein, Mr 32000 (DARPP−32), is overexpressed during gastric carcinogenesis. Gefitinib is a specific and effective EGFR inhibitor that has shown antitumor activity in clinical trials against gastrointestinal cancers. Gastric tumors can become resistant to gefitinib. However, molecular mechanisms that mediate resistance to gefitinib remain poorly understood. Methods: The expression of DARPP−32 in the multi-step carcinogenesis cascade was examined using IHC analysis. Cell survival was determined by clonogenic survival and ATP−Glo assays. Apoptosis was assessed by Annexin-V and immunoblot analyses. The association between DARPP−32 and EGFR was evaluated by immunofluorescence and co-IP assays. Results: The composite expression score progressively increased significantly from normal or gastritis to adenocarcinoma (p&lt;0.001). Overexpression of DARPP−32 in MKN-28 cells blocked gefitinib-induced apoptosis and increased the drug’s IC50 10−fold, compared to that of control cells (P&lt;0.01). And DARPP-32 expressing MKN−28 cells had activated the PI3K-AKT pathway as compared to control cells. The three−way co-IP experiments demonstrated the existence of DARPP-32, EGFR, and ERBB3 in the same protein complex. DARPP-32 enhanced EGFR-ERBB3 heterodimerization promoting phosphorylation of ERBB3, and then activated the PI3K-AKT pathway. Following treatment with gefitinib (25 μM) overnight, MKN−28 cells expressing DARPP-32 displayed stable protein levels of EGFR. The knockdown of endogenous DARPP-32 by DARPP-32 shRNA in SNU-16 cell lines reversed these signaling effects and increased sensitivity to gefitinib (p&lt;0.01). Conclusions: Our results suggest that DARPP-32 overexpression may participate in the progression to neoplasia. DARPP-32 also plays a role in increasing the stability of EGFR protein; DARPP-32 promotes resistance of gastric cancer cells to gefitinib by promoting interaction between EGFR and ERBB3 and activating PI3K–AKT signaling. DARPP-32 may have potential as a predictive biomarker in gastric cancer prognosis and clinical response to treatment.
Activity of the Aurora Kinase Inhibitor, MLN8237 (alisertib) Alone or in Combination with Ponatinib Against Imatinib-Resistant BCR-ABL-Positive Cells
Authors: Seiichi Okabe, Tetsuzo Tauchi, Seiichiro Katagiri, Yuko Tanaka, Kazuma Ohyashiki
Journal: Blood (2012)
Cord Blood (CB) Unit Mononuclear Cell (MNC) Dose: Effect on Transplantation Outcome and Relevance to Processing Method and CBU Selection.
Authors: Andromachi Scaradavou, Cladd Stevens, Ludy Dobrila, Tracy Zhu, Shanlong Jiang, Diana Daniels, Patricia E Taylor, Dorothy Sung, Maria S Albano, Pablo Rubinstein
Journal: Blood (2008)
KIR Ligand Incompatibility in HLA-Identical Sibling Nonmyeloablative Hematopoietic Stem Cell Transplantation for Hematologic Malignancies.
Authors: Jae H. Park, Andrew J. Yee, Thomas R. Spitzer, Susan L. Saidman, David T. Ting, Andrea Pannone, Jessica Reid, Steven McAfee, Bimalangshu R. Dey
Journal: Blood (2006)
A phase I/II study of adenovirus-mediated reduced expression in immortalized cells (REIC/DKK-3) gene therapy for prostate cancer: An interim report.
Authors: Katsumi Sasaki, Yasutomo Nasu, Masami Watanabe, Haruki Kaku, Ryuta Tanimoto, Daiki Kanbara, Toyohiko Watanabe, Hiroyuki Yanai, Hiromi Kumon
Journal: Journal of Clinical Oncology (2012)

161 Background: A new cancer therapeutic gene; REIC/Dkk-3 was found in Okayama university in 2000. In vivo experiments have demonstrated outstanding cancer-selective apoptosis effects and anti-cancer immunoactivity against various types of malignant tumors. With these positive experimental results, a phase I/II study of adenovirus-mediated REIC/Dkk-3 gene therapy for prostate cancer was initiated from January 2011 in Okayama university hospital. Methods: Two major inclusion criteria category were set up; A: A recurrence of prostate cancer following definitive endocrine therapy with/without metastasis, B: A localized prostate cancer which was considered high risk of recurrences following radical surgery according to a nomogram reported by Kattan et al. Replication-defective adenovirus vector expressing REIC/Dkk-3 (Ad-REIC) was injected directly into the prostate (or metastatic lesion in patients who received prostatectomy) in escalating doses from 1.0×10 10 to 1.0×10 12 viral particle (vp). Each patient in category A received total of 2 times viral injections every 4 weeks. Patients in category B also received total of 2 times viral injections every 2 weeks, then received radical prostatectomy 6 weeks after second viral injection. Results: Three patients in category A, and 9 patients in category B were entered the present study. No significant side effects were observed. In category B, signs of immunological responses in surgically removed specimens (apoptosis induction of cancer cells in TUNEL staining and infiltration of CD8 positive cells (CTL) in immunohistochemical staining) were observed in second dose. These responses were remarkably observed in the third dose. Conclusions: This initial and preliminary report suggests the favorable safety profile and positive clinical responses in a clinical trial of Ad-REIC gene therapy for prostate cancer.
Characteristics of the screen-failure (SF) patient population in an early castrate-resistant prostate cancer vaccine clinical trial: Lessons for future trial design.
Authors: Daniel A. Vaena, Pamela Zehr, Karen Griffith, Erica Brown, James A Brown, Julie Eastman, David Lubaroff
Journal: Journal of Clinical Oncology (2012)

241 Background: AdPSA is an investigational replication-deficient adenovirus-based PSA vaccine. A prior phase I trial in patients (pts) with metastatic CRPC showed safety and ability to generate immune responses. We are conducting a phase II trial in early CRPC in our comprehensive cancer center + VA. This study contains an analysis of the SF (post-informed consent) population. Methods: Patients with CRPC defined as rising PSA despite androgen deprivation therapy are eligible for this trial. Main eligibility criteria requires a bone scan, chest X-ray and abdomen pelvis CT without evidence of metastatic disease (any PSA or PSA doubling time allowed). Pts with metastatic disease are also eligible if they have a PSA doubling time greater than 6 months and a PSA less than 10 and are asymptomatic. Prior antiandrogens or ketoconazole are allowed, provided the PSA is rising. Prior chemotherapy or sipuleucel-T is not allowed. Results: 38 pts have been consented for the clinical trial, of which 21 pts have proceeded with study therapy. 17 pts were SF for the following reasons: 13 had positive CT and/or bone scans with exclusionary PSA or PSADT values, 1 had declining PSA prior to starting therapy, and for 3 pts initiation of study therapy was contraindicated (second cancer discovered on CT, aggressive pace of progression, and unrelated patient death). Median PSA was 10.2 for SF vs 1.9 ng/mL for treated pts. 6 SF patients had PSA &lt; 5 ng/mL. 26 pts had prior bicalutamide (12 SF, 14 treated group). Prior ketoconazole was rare in both groups. The vast majority of pts who were treated did not have metastatic disease. Conclusions: In a large academic cancer center, it is challenging but possible to find patients with early non-metastatic CRPC. Higher PSA may predict SF, but several patients with PSA &lt; 5 ng/mL also had metastases on screen. Prior antiandrogen is not a predictor for SF. Since this abstract only relates to patients who consented for the trial, the denominator of cancer center patients with early CRPC (but not eligible) is even larger. This information will help accrual estimates in cancer centers and feasibility assessment of early CRPC studies.