tbuckley/cabot-search huggingface dataset:
Akt Inhibitor Perifosine-Induced Cytotoxicity Is Associated with Significant Downregulation of Survivin in Human Multiple Myeloma (MM) Cells.
Authors: Teru Hideshima, Hiroshi Yasui, Laurence Catley, Noopur Raje, Dharminder Chauhan, Kenji Ishitsuka, Klaus Podar, Constantine Mitsiades, Yu-Tzu Tai, Sonia Vallet, Tanyel Kizitepe, Enrique Ocio, Hiroshi Ikeda, Yutaka Okawa, Hiromasa Hideshima, Nikhil C. Munshi, Paul G. Richardson, Kenneth C. Anderson
Journal: Blood (2006)
Phase II study of sunitinib and irinotecan in patients with recurrent high-grade glioma (HGG).
Authors: S. Grisanti, R. Pedersini, V. D. Ferrari, R. Liserre, F. Consoli, L. Poliani, M. Buglione, G. Rangoni, E. Montini, E. Simoncini
Journal: Journal of Clinical Oncology (2010)

e12537 Background: The prognosis of patients (pts) with recurrent HGG is poor with a median survival of 3 to 6 months. To date, no second line of treatment is recognized as standard. Enhanced angiogenesis has been recognized as a marker of HGG. Antiangiogenetic agents combined to irinotecan (I) have shown major antitumor activity in recurrent HGG. Sunitinib (S) is a selective inhibitor of multiple tyrosine kinases including VEGFR and PDGFR that crosses the blood-brain barrier. We investigated the safety and activity of the combination of S and I in the treatment of pts with recurrent HGG. We also analyzed tissue expression of markers of angiogenesis and dynamic contrast enhanced magnetic resonance imaging (DCE- MRI) as predictive factors of response. Methods: A total of 30 patients with recurrent HGG were screened between April 2008 and September 2009. Eligibility criteria included ECOG PS ≤ 2, prior RT and TMZ-based CT, measurable disease. Exclusion criteria included prior antiangiogenic therapy and prior intracranial hemorrhage or other bleeding diathesis. Primary endpoint was time-to-progression (TTP) defined as progression or death. Each 6-weeks cycle consisted of S administered at a starting dose 50 mg/day for 4 weeks and I at 180 mg/sqm administered every 2 weeks. After 2 cycles, patients were evaluated clinically and by DCE-MRI. Results: 6 pts were enrolled. Median age was 48 years (range 43-53). Median number of administered cycles was 3 (range 1- 5). All pts required reduction of the starting dose of S and the median dose of S was 25 mg/day. Overall, the treatment was well tolerated with no grade III-IV adverse events. Analysis of response included stable disease (SD) in 1 pt and progressive disease (PD) in 5 pts. Median TTP and OS were 1.5 months and 3 months, respectively. All pts experienced reduction of steroid and diuretics requirements while on treatment. DCE-MRI showed correlation between variations of cerebral blood volume (rCBV) and antiangiogenic activity of S. Conclusions: In this study, the combination of S and I at the tested doses is safe but showed insufficient antitumor activity despite transient antiedema effect. A modified schedule or S dose intensification could provide clinical advantage in selected pts. No significant financial relationships to disclose.
A multi-center phase II study of S-1 plus paclitaxel as first-line therapy in patients with advanced or relapsed gastric cancer
Authors: J. J. Lee, S. Y. Kim, H. C. Chung, K. H. Lee, H. S. Song, I. S. Woo, Y. S. Hong, W. K. Kang, J. H. Choi, I. S. Choi
Journal: Journal of Clinical Oncology (2007)

4634 Background: S-1 is an oral prodrug of 5-fluorouracil (5-FU) including two modulators to enhance the antitumor effect and to decrease gastrointestinal toxicity. Paclitaxel has the synergistic antitumor effect with 5-FU. This study were planned to evaluate the efficacy and safety of S-1 and paclitaxel combination therapy in advanced gastric cancer. Methods: Eligible patients had untreated advanced or relapsed gastric cancer with measurable lesion(s), histologic proof, ECOG PS 0–2, adequate organ function, and signed informed consent. Treatment consisted of S-1 35mg/m 2 p.o. b.i.d. on days 1–14 plus paclitaxel 70mg/m 2 i.v. on days 1&amp; 8 of a 21-day cycle. Measurable and/or unmeasurable lesion was assessed after every 2 courses with RECIST criteria. Results: A total of 56 patients (M/F=37/19) were enrolled. The median age was 59 years with advanced (n=43) and relapsed (n=13) gastric cancer. The common metastatic lesions were abdominal lymph nodes (71%), liver (39%), and peritoneum (21%). Out of 53 evaluable patients, there was 1 (2%) CR, 25 (47%) PRs, 21 (40%) SDs, and 6 (11%) PDs. Objective tumor response was 49%. Median duration of response was 5.4+months after the confirmation of response. Median follow-up was 9.6 month. Median PFS was 7.7 months and median survival was 14.6 months. Median number of cycle was 6 (range, 1–14). The relative dose intensity of S-1 and paclitaxel was 93%, both. The most common causes of delayed cycle and dose reduction were neutropenia and diarrhea, respectively. All 56 patients were assessed for safety. This treatment was well tolerated with grade 3/4 neutropenia in 14%/5%, grade 3 febrile neutropenia in 5%, grade 2/3 N/V in 21%/0%, anorexia in 18%/2%, diarrhea in 9%/4%, stomatitis in 7%/4%, and neuropathy 7%/0% of patients. Conclusions: S-1 and paclitaxel combination chemotherapy showed significant antitumor effect with manageable and tolerable toxicities in patients with advanced gastric cancer. (This study was partially supported by a grant of the Korea Health 21 R&amp;D Project, Ministry of Health &amp; Welfare, Republic of Korea (0412-CR01–0704–0001)) No significant financial relationships to disclose.
Triple-negative invasive breast cancer (TNBC): Mammographic, US, and MR imaging features according to androgen receptor (AR) expression.
Authors: Woo Kyung Moon
Journal: Journal of Clinical Oncology (2014)

159 Background: A subset of TNBC is characterized by an androgen gene signature and early clinical trials have demonstrated clinical benefit with the use of the AR antagonist, bicalutamide, for the treatment of patients with AR+, estrogen receptor/progesterone receptor- breast cancer. Methods: AR expression was assessed immunohistochemically in 125 patients (median age; 54 years, range; 26-82 years) with TNBC from a consecutive series of 1,086 operable invasive breast cancers. Two experienced breast imaging radiologists (6 and 24 years of experience, respectively) reviewed the mammograms, US, and MR images without knowledge of clinicopathologic findings. The imaging and pathologic features of 33 AR-positive TNBCs were compared with those of 92 AR-negative TNBCs by using the Fisher’s exact or chi-squared tests. Results: AR expression in TNBC is significantly associated with mammographic findings (P &lt; 0.001), lesion type at MR imaging (P &lt; 0.001), and mass shape or margin at ultrasound (P &lt; 0.001; P= 0.002). The highest PPVs for AR-positive cancer were non-mass enhancement on MR imaging (PPV, 1.00; 95% CI: 0.61, 1.00), calcifications only seen on mammography (PPV, 1.00; 95% CI: 0.37, 1.00), and spiculated masses on US (PPV, 1.00; 95% CI: 0.22, 1.00). Conclusions: AR-positive and AR-negative tumors have distinct imaging features in TNBC. The presence of calcifications or focal asymmetries at mammography, the presence of echogenic halo or non-complex hypoechoic masses at US, masses with irregular shape or indistinct margins at mammography and US, and masses with irregular shape or spiculated margins, or non-mass lesions at MR imaging were associated with AR expression in TNBC. These imaging features may be used to predict AR status, which could assist in treatment planning, prediction of response, and assessment of prognosis for patients with TNBC.
The long-term impact of surgical complications after resection of stage I non-small cell lung cancer: A population-based survival analysis.
Authors: N. M. Rueth, H. M. Parsons, S. S. Groth, E. B. Habermann, B. A. Virnig, T. M. Tuttle, R. S. Andrade, M. Maddaus, J. D'Cunha
Journal: Journal of Clinical Oncology (2010)

6113 Background: Surgical morbidity may play an important role in long-term cancer survival. Because surgical resection of early stage non-small cell lung cancer (NSCLC) is primary therapy, we sought to determine the long-term impact of surgical complications for patients undergoing resection of stage I NSCLC. Methods: Using the Surveillance, Epidemiology, and End-Results-Medicare linked database (2000- 2005), we identified patients who underwent wedge resection, segmentectomy, or lobectomy for stage I NSCLC. We identified in-hospital, postoperative complications (pulmonary, cardiac, and systemic) from ICD-9 diagnosis codes. We constructed a logistic regression model to determine patient, tumor, and treatment characteristics associated with in-hospital postoperative complications. To assess the association between in-hospital complications and long-term cancer-specific survival (CSS) for those patients surviving the initial 30 days after surgical resection, we performed unadjusted survival analyses using the Kaplan Meier method (α = 0.05). Results: 5,856 patients met initial inclusion criteria. The overall in-hospital, postoperative complication rate exceeded 40%; arrhythmia was the most common complication, followed by respiratory failure. Complications were predicted by older age, gender, larger tumor size, and surgical procedure. Patients undergoing > 1 resection were significantly more likely to experience a complication. The 30-day mortality rate was 3.9% (n = 230). For the 5,626 remaining patients who survived their initial 30 days postoperatively, the 5-year CSS was significantly poorer for those who had an in-hospital, postoperative complication (82.2%) compared to those who did not (86.5%, p < 0.001). Overall survival was also significantly worse (p < 0.001). Conclusions: In-hospital, postoperative complications have a negative impact on 5-year CSS after surgical resection of stage I NSCLC. Importantly, our study suggests that surgical complications may impact survival well after the initial perioperative event. These findings may have important implications for best practice guidelines. No significant financial relationships to disclose.
Cardiac involvement in patients with sorafenib or sunitinib treatment for metastatic renal cell carcinoma
Authors: M. Schmidinger, U. M. Vogl, C. Schukro, A. Bojic, M. Bojic, H. Schmidinger, C. C. Zielinski
Journal: Journal of Clinical Oncology (2007)

5110 Background: Tyrosine-kinase inhibitors (TKI) of the VEGF and PDGF-receptor have significant clinical activity in patients with renal cell carcinoma (RCC). These agents target the VHL-hypoxia-inducible gene pathway and lead to inhibition of hypoxia- inducible factor (HIF)-induced gene products. Physiologically, HIF-1 related gene products are important mediators of myocardial response to ischemia, myocardial remodeling, peri-infarct vascularisation and vascular permeability. The aim of this prospective observational study was to investigate clinical and biochemical signs of myocardial damage in patients undergoing TKI-treatment for RCC. Methods: 73 consecutive patients (median age 65, range 44–68) intended for TKI treatment were analyzed for medical history of coronary artery disease (CAD) and risk-factors. Measurements of biochemical markers of cardiac damage (creatine kinase MB -CK-MB- and cardiac troponin T -cTNT-) and electrocardiogram (ECG) were performed before treatment. In patients developing cardiac symptoms during TKI treatment and/or at occurrence of CK-MB or TNT elevations, changes in ECG were analyzed and patients underwent echocardiography. Results: All patients had normal CK-MB and TNT levels at baseline. 17 patients (23%) developed (week 2–32 of treatment) significant CK-MB elevation, (TNT n=5), with clinical symptoms in 7 patients. No patient had uncontrolled hypertension. Detailed ECG’s comparison before and during treatment revealed significant changes in 10 out of 17 patients, such as ST-segment depression or elevation, T-wave changes and symptomatic AV-conduction disturbance, requiring pacemaker-implantation. 3 patients underwent coronary angiography with one patient showing acute coronary artery occlusion and myocardial infarction. 6 out of 17 patients had abnormal findings on echocardiography, such as reduced left ventricular function Conclusions: TKI-induced HIF-inhibition may be associated with severe myocardial damage. The underlying mechanism may not necessarily be caused by overt coronary artery occlusion. ECG-changes and biochemical markers are the most important indicators in the preclinical stage. Therefore, careful cardiac monitoring during TKI-treatment is strongly recommended. No significant financial relationships to disclose.
Mammaglobin expression in leukapheresis products is a predictive marker of poor prognosis in women with high-risk breast cancer
Authors: P. F. Ferrucci, C. Rabascio, C. Mazzetta, A. Agazzi, E. Cocorocchio, S. Cinieri, F. A. Peccatori, F. Bertolini, G. Martinelli
Journal: Journal of Clinical Oncology (2004)

9596 Background: We investigated the incidence and prognostic relevance of tumor cell detection (TCD) in G-CSF-mobilized peripheral blood progenitor cells collections (PBPCC), using Cytokeratyn (CK), Maspin (MAS) and Mammaglobin (MAM) genes as epithelial cell markers. The population chosen for the evaluation was stage III breast cancer patients (BC pts) undergoing high dose chemotherapy and autologous transplantation with PBPC. Methods: 194 pts were enrolled in the study and analyzed for TCD on 481 PBPCC before chemotherapy administration. CK, MAS and MAM genes expression were investigated by Reverse Transcriptase Nested Polimerase Chain Reaction (RT-PCR). CK expressing samples were also hybridized to a radiolabelled internal probe in order to reduce false positive results. Sensitivity and specificity was assessed on 37 controls (12 cell lines, 12 healthy donors and 13 non-epithelial malignancies). Each of the known prognostic variables (age, stage, lymph nodes status, receptor status, c-ErbB2 status, Ki67 status) was analyzed in relation to pts survival (OS) and relapse free survival (RFS), both individually and together with CK, MAS and MAM expression on PBPCC. Results: After three years follow-up, the estimated proportion of alive pts was 84% (95%CI=[76.3, 88.5]), while the estimated proportion of pts free of relapse was 61% (95%CI=[53.9, 69.2]). 176 of 194 pts (91%) had contaminated PBPCC by at least one positive sample for any of the marker evaluated. PBPCC frequency of CK, MAS and MAM positivity (+) was 71%–36% and 17% respectively. MAM expression on PBPCC was associated with an increased risk of relapse (p=0.003), while CK and MAS expression were not associated with changes in either RFS or OS. Conclusions: MAM gene expression on leukapheresis products of high risk BC pts is an indicator of poor prognosis. The method of evaluation is simple, reproducible and opens new tools in the evaluation of the role played by tumor cells in apheresis products and their potential to cause metastasis. No significant financial relationships to disclose.
Pilot remission induction therapy with idarubicin, plus intensified dose of Ara-C and priming with granulocyte colony-stimulating factor for acute myeloid leukemia
Authors: Y. Cho, J. Baek, S. Sohn, Y. Chae, D. Kim, J. Kim, D. Yang, Y. Kim, J. Lee, H. Kim
Journal: Journal of Clinical Oncology (2006)

16516 Background: The sensitization of leukemic cells with hematopoietic growth factors can enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML). Intensified remission induction (RI) therapy can also improve the treatment results for AML. Therefore, the current trial attempted to evaluate the efficacy and toxicity of granulocyte colony-stimulating factor (G-CSF) priming and a dose intensification of Ara-C in RI chemotherapy for AML. Methods: A total of 29 patients with newly diagnosed AML received G-CSF-priming RI chemotherapy consisting of idarubicin (12 mg/m 2 , D1–3), G-CSF (150 ug/m 2 , D3–8), and Ara-C (500 mg/m 2 , bid, D4–8), and the outcomes were compared with those for a historical group treated with a standard regimen consisting of idarubicin (12 mg/m 2 , D1–3) and Ara-C (100 mg/m 2 , D1–7). Results: There was no difference in the sex, age, subtype, and cytogenetic risk between the two groups. The complete remission (CR) rate and treatment-related mortality (TRM) were 72% and 17% for G-CSF-primed group and 71% and 10% for the historical group, respectively (p = 0.89 and p = 0.32). The time to neutrophil and platelet recovery did not differ significantly between the two groups (25 days vs. 24 days, p=0.17; 24 days vs. 23 days, p = 0.23, respectively). Similarly, the duration of fever was also not significantly different (5 days vs. 7 days, p = 0.58). Thirteen patients (45%) experienced fever and 5 patients (17%) manifested skin rashes during the G-CSF priming. After a median follow-up of 336 days, the 1-year overall survival (OS), disease-free survival (DFS), and event-free survival (EFS) rates were 72% vs. 63% (p = 0.83), 74% vs. 56% (p = 0.059), and 53% vs. 38% (p = 0.32), respectively. Conclusion: The G-CSF-priming RI regimen with an intensified dose of Ara-C did not show a superior efficacy when compared with a standard regimen, yet did produce a slightly longer DFS. Therefore, the sensitization of leukemic cells with growth factors and dose intensification would only seem to be a clinically applicable means to enhance the efficacy of RI chemotherapy in selected patients with AML, thereby warranting further studies focusing on specific subgroups of AML patients. No significant financial relationships to disclose.
P-184 nab-Paclitaxel (nab-P) plus gemcitabine (Gem) for patients with advanced pancreatic cancer who have cholestatic hyperbilirubinemia (CH) secondary to bile duct obstruction: a phase I safety and pharmacokinetics study
Authors: H. Riess, V. Kunzmann, P. Philip, T. Seufferlein, D. McGovern, P. Chen, A. Romano, R. Ramanathan
Journal: Annals of Oncology (2015)
Phase II trial of functional imaging-optimized stereotactic fractionated radiotherapy plus temozolomide for recurrent high-grade glioma
Authors: C. Nieder, N. Wiedenmann, S. Stark, A. L. Grosu
Journal: Journal of Clinical Oncology (2004)

1552 Background: Stereotactic fractionated radiotherapy (SFRT) is a valuable treatment option for recurrent high-grade glioma. Its therapeutic ratio might be improved by functional imaging-optimized treatment planning. After this approach has been evaluated in 16 patients, additional chemotherapy with temozolomide was added to the regimen in a single-institution phase II trial. Methods: 16 patients entered the SFRT alone trial, 30 patients received SFRT plus temozolomide. For treatment planning with the BrainLAB system, the gross tumor volume was defined by C11-methionine PET/CT/MRI image fusion. Maximum diameter was less than 4 cm. Mean age was 50 years. 37 patients had glioblastoma multiforme, 8 anaplastic astrocytoma and 1 anaplastic oligodendroglioma. Previous radiotherapy dose was 54–60 Gy (median interval to retreatment 17 months). Total dose was 30 Gy in 6 fractions. Temozolomide 200 mg/m2/day every 28 days was started before SFRT with 1–2 cycles. After SFRT, 4+ cycles were added. Patients were followed with MRI or CT every other cycle. Results: Median survival was 11 months for patients who received SFRT plus temozolomide and 6 months for patients treated with SFRT alone (p=0.02). No acute neurologic toxicity grade II or higher was observed. No grade IV hematologic toxicity was observed. Signs of radionecrosis were observed in 3 patients. However, surgical resection revealed both tumor and necrosis. Conclusions: This is the first study of functional imaging-optimized SFRT plus temozolomide. It demonstrates the feasibility and safety of this approach. Our institutional retrospective comparison suggests a significant survival advantage from combined modality treatment which needs to be confirmed prospectively. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Essex Pharmaceuticals
Consequences of expression and release of MIC molecules by malignant cells
Authors: H. R. Salih, A. Wagner, L. Kanz, H.-G. Rammensee, A. L. Steinle
Journal: Journal of Clinical Oncology (2004)

9708 Background: NKG2D-ligands (NKG2DL) mark malignant cells for recognition by cytotoxic lymphocytes via the immunoreceptor NKG2D. The human NKG2DL MICA and MICB are expressed on tumors of epithelial and hematopoietic origin, and recently we reported that MICA is released by tumor cells in a soluble form (sMICA) and can be detected in sera of patients (Salih et al., J. Immunol. 169: 4098. 2002). NKG2D-mediated immune responses are critically dependent on the expression levels of NKG2DL; therefore, reduction of MIC protein expression by release from the cell surface would potentially reduce immunogenicity of tumors. In addition, it has been reported that sMICA downregulates NKG2D expression leading to functional impairment of cytotoxic lymphocytes (Nature 17;419: 734 2002). Methods: Tumor cells were cultured in the presence of a metalloprotease-inhibitor, then cells were analysed for MICB surface expression by FACS and culture supernatants were investigated by ELISA for soluble MICB (sMICB). In addition, sera from patients with colon carcinoma, rectum carcinoma, stomach carcinoma and AML were investigated for sMICB, and the results were compared to levels of sMICA in these patients. NK cells were cultured in the presence or absence of soluble or cell bound MIC protein and the effects on NKG2D surface expression were followed by FACS. Results: We found high levels of sMICB in sera of tumor patients compared to healthy controls; release of sMICB from tumor cells is blocked by inhibition of metalloproteinases, concomitantly causing accumulation of MICB on the cell surface. MIC-protein causes downregulation of surface NKG2D on NK in cell-bound, but not in soluble form. Furthermore, we evaluated both sMICA and sMICB as tumor markers and demonstrate significant differences in sMICA or sMICB levels among various tumor entities. Conclusions: Shedding of MICB by tumor cells may modulate NKG2D mediated tumor immune surveillance. Determination of soluble MIC protein levels may be implemented as an diagnostic marker in patients with malignancies. Further prospective studies are currently being conducted addressing the value of each MIC molecule as a tumor marker in different tumor entities. No significant financial relationships to disclose.
Seahorse Brood Pouch Transcriptome Reveals Common Genes Associated with Vertebrate Pregnancy
Authors: Camilla M. Whittington, Oliver W. Griffith, Weihong Qi, Michael B. Thompson, Anthony B. Wilson
Journal: Molecular Biology and Evolution (2015)

Viviparity (live birth) has evolved more than 150 times in vertebrates, and represents an excellent model system for studying the evolution of complex traits. There are at least 23 independent origins of viviparity in fishes, with syngnathid fishes (seahorses and pipefish) unique in exhibiting male pregnancy. Male seahorses and pipefish have evolved specialized brooding pouches that provide protection, gas exchange, osmoregulation, and limited nutrient provisioning to developing embryos. Pouch structures differ widely across the Syngnathidae, offering an ideal opportunity to study the evolution of reproductive complexity. However, the physiological and genetic changes facilitating male pregnancy are largely unknown. We used transcriptome profiling to examine pouch gene expression at successive gestational stages in a syngnathid with the most complex brood pouch morphology, the seahorse Hippocampus abdominalis. Using a unique time-calibrated RNA-seq data set including brood pouch at key stages of embryonic development, we identified transcriptional changes associated with brood pouch remodeling, nutrient and waste transport, gas exchange, osmoregulation, and immunological protection of developing embryos at conception, development and parturition. Key seahorse transcripts share homology with genes of reproductive function in pregnant mammals, reptiles, and other live-bearing fish, suggesting a common toolkit of genes regulating pregnancy in divergent evolutionary lineages.