tbuckley/cabot-search huggingface dataset:
GA101, a Novel Humanized Type II CD20 Antibody with Glycoengineered Fc and Enhanced Cell Death Induction, Exhibits Superior Anti-Tumor Efficacy and Superior Tissue B Cell Depletion In Vivo.
Authors: Pablo Umana, Moessner Ekkehard, Bruenker Peter, Klingner Gabriele, Puentener Ursula, Tobias Suter, Roger Grau, Carla Schmidt, Sylvia Herter, Christian Gerdes, Adam Nopora, Monika Patre, Samuel Moser, Peter Sondermann, Luise Wheat, Martin J.S. Dyer, Sibrand Poppema, Sabine Bauer, Manfred Kubbies, Pamela Strein, Georg Fertig, Thomas Friess, Karim Dabbagh, Joe DalPorto, Christian Klein
Journal: Blood (2007)
Abstract 2908: The clinical significance of Nrf2 overexpression in esophageal cancer
Authors: Yuki Kitano, Yoshifumi Baba, Kensuke Yamamura, Hironobu Shigaki, Kousuke Mima, Junji Kurashige, Masaaki Iwatsuki, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Hideo Baba
Journal: Cancer Research (2016)

Abstract Background: NF-E2-related factor 2 (Nrf2) is a key transcription regulator for antioxidant and detoxification enzyme and is overexpressed in various cancer cells. In this study, prognostic significance of Nrf2 expression in esophageal cancer was investigated. In addition, we examined the relationship between the expression of Nrf2 and cell proliferation using in vitro assay. Methods: We immunohistochemically evaluated the protein expression of Nrf2 in the surgically resected specimens in 83 esophageal cancer patients. And ten esophageal cancer cell lines were utilized in vitro assay. Results: We examined the protein expression of Nrf2 in 10 esophageal cancer cell lines. TE-11 cell had the highest expression of Nrf2, while KYSE30 had the lowest expression of Nrf2. Importantly, there was no correlation between the protein level and mRNA level of Nrf2 in these cell lines. The cell proliferation was inhibited in TE-11 cells, and not inhibited in KYSE30 cells by treatment with Nrf2-siRNA. Moreover, Flow Cytometry Assay revealed that knockdown of Nrf2 by siRNA arrested the cell cycle at G1 phase in TE-11 cells. In immunohistological study, Nrf2 was predominantly identified in the nucleus of esophageal cancer cells and the expression level of Nrf2 was higher in the tumor than normal esophageal epithelium (P&amp;lt;0.001). There was no relationship between Nrf2 protein expression and clinicopathological characteristics. The overall survival of the high-Nrf2 expression group was significantly poorer than that of low-Nrf2 expression group (P = 0.004). Conclusions: The expression of Nrf2 is up-regulated in esophageal cancer cell lines and resected tumor specimen. Our in vitro assay revealed that Nrf2 appeared to support cancer cell proliferation. Therefore, strategies to pharmacologically manipulate the level and / or activity of Nrf2 may have potential to reduce tumor growth and improve the prognosis of esophageal cancer patients. Citation Format: Yuki Kitano, Yoshifumi Baba, Kensuke Yamamura, Hironobu Shigaki, Kousuke Mima, Junji Kurashige, Masaaki Iwatsuki, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. The clinical significance of Nrf2 overexpression in esophageal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2908.
Combination of a peptide-modified gellan gum hydrogel with cell therapy in a lumbar spinal cord injury animal model
Authors: Eduardo D. Gomes, Sofia S. Mendes, Hugo Leite-Almeida, Jeffrey M. Gimble, Roger Y. Tam, Molly S. Shoichet, Nuno Sousa, Nuno A. Silva, António J. Salgado
Journal: Biomaterials (2016)
Impact of FOLFOXIRI regimen on early “conversion” and long-term outcome in patients with initially unresectable colorectal liver metastases.
Authors: Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Shuichi Iwahashi, Yu Saito, Shinichiro Yamada, Jun Higashijima, Chie Takasu
Journal: Journal of Clinical Oncology (2015)

416 Background: In our principle, hepatectomy is the first choice for liver metastases (mets) from colorectal cancer whenever future remnant liver is over 40% in volume. Recently, FOLFOXIRI (5-FU/LV+Oxaliplatin+Irinotecan) plus bevacizumab (Bev) regimen was reported to be high rates of pathologic responses and necrosis of colorectal liver metastases (CLMs) without increasing liver toxicity (Br J Cancer 2013). The aim of this retrospective study is to clarify impact of FOLFXIRI plus molecular targeted drugs on initially unresectable CLMs. Methods: Among 81 patients with initially unresectable liver mets, 59 had chemotherapy (CTx), including 10 old CTx (-2003) and 49 new CTx (2004- ) using new drugs such as oxaliplatin. Regimen of FOLFOXIRI + molecular target drugs, consisting of Bev in 12 and C/P-mab in 2, was applied to 14 patients. “Conversion” rate and the period until “Conversion”, and overall survival (OS) were compared between FOLOFOXIRI group and other regimen group. Pathological and morphological responses were also examined. Results: “Conversion” was not obtained in old CTx group. In new CTx group, “Conversion” was achieved in 21 patients (43%). OS in “Convresion” group was better than “non-conversion” group (3-year survival: 70 % vs. 15 %). “Conversion” rate in FOLFOXIRI group was higher than that in other regimen group (64% vs. 34%). The period until “Conversion” in FOLFOXIRI group was shorter than that in other regimen group (6.2 cycles vs. 16.1 cycles). Furthermore, tumor necrosis rate in FOLFOXIRI group (80 %) was higher than that in other regimen group (47 %), and morphologic response (optimal/partial) in FOLFOXIRI group (33 % / 44 %) was higher than in other regimen group (8 % / 33 %). Prognosis after “Conversion” in FOLFOXIRI group was better than that in other regimen group (3-year survival: 80 % vs. 33 %). In addition, time to surgical failure (TSF) in FOLFOXIRI group tended to be better than that in other regimen group. Conclusions: FOLFOXIRI + molecular target drugs is highly effective in order to obtain early conversion and better long-term outcome after ”Conversion” for initially unresectable CLMs.
Abstract 163: Genetic difference between multicentric carcinogenesis and intrahepatic metastasis of hepatocellular carcinoma
Authors: Yutaka Midorikawa, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Shingo Tsuji, Genta Nagae, Tadatoshi Takayama, Hiroyuki Aburatani
Journal: Cancer Research (2016)

Abstract Multiple hepatocellular carcinoma (HCC) is categorized into 2 types; multicentric hepatocarcinogenesis (MC) and intrahepatic metastasis (IM). Although discrimination of the types of multiple HCC is of clinical importance, it is quite difficult to determine it correctly even after histological diagnosis. In order to classify multiple HCC into MC and IM, we compared pairs of multiple HCC samples from 12 patients who were clinically diagnosed MC, 6 patients with IM with regard to molecular aberrations, and 2 patients with pairs of primary HCC and extrahepatic metastasis such as adrenal grand and lung metastasis. Exome sequence showed that 125 mutations (90.6%) per patient with IM were common, which were consistent with the result of a pair of primary HCC and extrahepatic metastasis. On the other hand, 138 somatic mutations per tumor, and no common somatic mutations were identified in the 7 patients with MC. Especially only a few passenger mutations were different between IM specimens suggesting that IM pairs developed from the common ancestor. In contrast, 5 patients who clinically diagnosed MC had common mutations (41.7%), which indicates that pairs of HCC of these patients were genetically IM. Notably, mutation signatures obtained from exome sequence data of 2 nodules from the same patients with IM were similar, while those from patients with MC were different by profiling analysis. On the other hand, methylation profile shows that 2 HCC samples from the same patients with MC as well as IM were classified into the same cluster; the methylation status from the different ancestor is similar, and not altered through carcinogenesis. Taken together, comparison of mutations in a pair of HCCs makes it possible to classify multiple HCCs into MC and IM, which is difficult to be correctly determined in clinical practice, and is available to make treatment plans for multiple HCC patients. Furthermore, methylation status of 2 nodules of MC from same patient were similar, while those of mutation signatures were different, which suggests that the epigenomic changes are the earlier event prior to the genomic alterations. Citation Format: Yutaka Midorikawa, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Shingo Tsuji, Genta Nagae, Tadatoshi Takayama, Hiroyuki Aburatani. Genetic difference between multicentric carcinogenesis and intrahepatic metastasis of hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 163.
Abstract 1816: Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells
Authors: Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Seonhee Lim, Soyoung Sim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Journal: Cancer Research (2016)

Abstract The short-chain fatty acid, α-lipoic acid (ALA) is a powerful antioxidant used for treatment of diabetic neuropathy. Recent studies suggested the possibility of ALA as a potential anti-cancer agent, because it could activate adenosine monophosphate activated protein kinase (AMPK) and inhibit transforming growth factor-β (TGFβ) pathway. We evaluate the effects of ALA on thyroid cancer cell proliferation, migration, and invasion. We performed in vitro cell proliferation analysis with BCPAP, HTH-83, CAL-62, and FTC-133 cells. ALA suppressed cell proliferation through activation of AMPK and subsequent down-regulation of mammalian target of rapamycin (mTOR)-S6 signaling pathway. Low-dose ALA, which had minimal effects on cell proliferation, also decreased cell migration and invasion of BCPAP, CAL-62, and HTH-83 cells. ALA inhibited epithelial mesenchymal transition (EMT) evidently by increase of E-cadherin and decreases of activated β-catenin, vimentin, snail, and twist in these cells. ALA suppressed TGFβ production and inhibited induction of p-Smad2, and twist by TGFβ1 or TGFβ2. These findings indicate that ALA reduces thyroid cancer cell migration and invasion through suppression of TGFβ production and inhibition of TGFβ signaling pathways. ALA also significantly suppressed tumor growth in mouse xenograft model using BCPAP and FTC-133 cells. This is the first study to show anti-cancer effect of ALA on thyroid cancer cells. ALA could be a potential therapeutic agent for advanced thyroid cancer, as an adjuvant therapy with other systemic therapeutic agents. Citation Format: Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Seonhee Lim, Soyoung Sim, Tae Yong Kim, Young Kee Shong, Won Bae Kim. Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1816.
Retrospective database analysis of the clinical effect of zoledronic acid on fractures and mortality among patients with genitourinary (GU) cancer and bone metastases (BM) in a managed care plan.
Authors: S. Thayer, S. Kaura, H. J. Henk
Journal: Journal of Clinical Oncology (2010)

e19518 Background: For cancer pts with BM, skeletal complications (SC) are common. Skeletal complications such as fracture may increase morbidity and mortality and reduce quality of life. Zoledronic acid (ZOL) is an intravenous bisphosphonate (IVBP) with efficacy in reducing or delaying the incidence of SCs due to BM. This analysis was performed to assess the real-life benefit of long-term ZOL use. Methods: A claims-based analysis using commercial and Medicare data from a large, U.S.-managed care plan and from a database consisting of 45 health plans was used to evaluate mortality and risk of fracture in pts treated with ZOL, compared with those who were not treated with an IVBP. Pts age 18+ with a prostate cancer (PC), bladder cancer (BlC), or renal cell carcinoma (RCC) diagnosis between Jan 2001 and Dec 2006 as well as a BM were included. Continuous enrollment in the health plan for 6 months prior to the index date, with no evidence of BM or IVBP. Pts were followed until disenrollment, therapy switch, or end of study. Risk of fracture and mortality were assessed. Results: The analysis included 6,347 pts (4,976 PC, 941 RCC, and 430 BlC) with a mean age of 68.9 years (±11.12); approximately 23% were treated with ZOL. Incidence of fracture was greater in the non-IVBP group (IRR = 1.43, 95%CI = 1.20, 1.73). Mortality was also greater in the non-IVBIS group (IRR = 1.81, 95%CI = 1.42, 2.35). Overall, pts who had higher levels of persistency on ZOL experienced reduced risk for fractures than those with a lower persistency of treatment (Table 1). Average time between BM Dx and ZOL initiation was between 76 (BIC) and 118 days (RCC). Conclusions: This retrospective analysis showed that in pts with GU cancers and BM, ZOL treatment is associated with lower risk of fracture and decreased mortality. Among ZOL treated pts, regular infusions with ZOL (increased persistence with ZOL) resulted in a significant reduction in the risk of developing pathological fractures. Risk of fracture per 100 person-years by ZOL persistency Persistency category (days) Fracture No-IVBIS 10.50 31-180 9.48 181-365 4.68 365-546 5.12 547+ 3.19 P value: Test for trend 0.0009 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Use of primary G-CSF and its impact on febrile neutropenia, hospitalization, dose delivery, and survival in patients with metastatic testicular germ-cell tumour (MT-GCT).
Authors: Jenny J. Ko, Tehmina Asif, Haocheng Li, Nimira S. Alimohamed, Thao Phuong Nguyen, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2015)

e15573 Background: The benefits of routine use of prophylactic G-CSF with first-line chemotherapy in patients with MT-GCT are unclear. We evaluated patterns of G-CSF use and correlated with patient outcomes. Methods: We included consecutive patients who received first-line chemotherapy for MT-GCT (January 1990-December 2013) at two Canadian tertiary cancer centres. Use of G-CSF was correlated with dose delivery, febrile neutropenia, hospitalization, and survival. Results: 346 patients were included in the final analysis. Median age at diagnosis was 32 years (range 15-89). 219 (63%) were in the IGCCCG favourable risk group; 72 (21%) in the intermediate; 53 (16%) in the poor. 105 (30%) had classic seminoma; the rest, non-seminoma. 317 (92%) had first-line chemotherapy, of which 275 (87%) received BEP chemotherapy. 63 (18%) received G-CSF during chemotherapy – 51 as primary prophylaxis, 12 as secondary prophylaxis. Primary G-CSF use was associated with reduced rates of febrile neutropenia (12 vs. 15%, p < 0.001), dose reduction (0 vs 10%, p = 0.03), hospitalization due to febrile neutropenia (6 vs. 13%, p < 0.001), and hospitalization due to any cause (18 vs. 49% p < 0.001). Patients who received primary G-CSF had trends towards less dose delay (6 vs. 13%, p = 0.33). Among patients who were hospitalized due to febrile neutropenia (n = 35), only 9% had primary G-CSF use (p < 0.001). Bleomycin-related lung toxicity was not significantly increased with G-CSF use (13 vs. 14%, p = 0.10). The number of G-CSF cycles was significantly correlated with rates of febrile neutropenia (p = 0.01). Patients who received primary GCSF had similar 5 yr OS (92 vs. 90%, p = 0.88) and DFS (88 vs. 80%, p = 0.22) compared with those who did not receive primary GCSF, with median follow-up periods of 35 months (primary G-CSF) and 107 months (no primary G-CSF). Conclusions: Our data suggest that the use of primary G-CSF may reduce hospitalization, dose reduction and febrile neutropenia without increasing bleomycin lung toxicity in patients receiving first-line chemotherapy for MT-GCT.
Meeting Report: The Role of the Mobilome in Cancer
Authors: Daniel Ardeljan, Martin S. Taylor, Kathleen H. Burns, Jef D. Boeke, Michael Graham Espey, Elisa C. Woodhouse, Thomas Kevin Howcroft
Journal: Cancer Research (2016)

Approximately half of the human genome consists of repetitive sequence attributed to the activities of mobile DNAs, including DNA transposons, RNA transposons, and endogenous retroviruses. Of these, only long interspersed elements (LINE-1 or L1) and sequences copied by LINE-1 remain mobile in our species today. Although cells restrict L1 activity by both transcriptional and posttranscriptional mechanisms, L1 derepression occurs in developmental and pathologic contexts, including many types of cancers. However, we have limited knowledge of the extent and consequences of L1 expression in premalignancies and cancer. Participants in this NIH strategic workshop considered key questions to enhance our understanding of mechanisms and roles the mobilome may play in cancer biology. Cancer Res; 76(15); 4316-9. ©2016 AACR.
Clinical correlation of genomic mutations in small cell lung cancer.
Authors: Afshin Dowlati, Pingfu Fu, Mary Beth Lipka, Gary Wildey
Journal: Journal of Clinical Oncology (2015)

7575 Background: Genomic studies in small cell lung cancer (SCLC) lag far behind those performed in non-small cell lung cancer (NSCLC). Unlike NSCLC, where specific mutations such as ALK and EGFR are associated with distinct clinical behavior, no such data exists for SCLC. We have established a clinical- pathologic database on all SCLC patients treated at our medical center and recently added genomic analysis. Methods: Targeted exome sequencing data of 324 genes was obtained on a total of 36 patients. Genes were organized for analysis into two groups: (I) genes with mutations validated to be oncogenic, and (II) genes harboring any detectable mutation, validated or not. The specific type of mutation was not considered, only its presence/absence, except for TP53, which were additionally characterized as either disruptive (D) or non-disruptive (ND). Principal clinical correlates were OS, PFS, and chemo-response. Survivor distribution was estimated using Kaplan-Meier methods and difference of OS, PFS between/among groups was examined by log-rank test. The effect of continuous measurements including age, and number of genes alternated on survival (OS, PFS) was estimated using Cox model. Results: The cohort was typical for SCLC, containing a majority of extensive disease (78%), chemo-sensitive (66%) male (56%) patients. The median OS for all patients was 11.4 mo (95% CI: 7.9-55.5 mo). While no Group I genes significantly correlated with OS, PFS was significantly worse for patients with no TP53 mutation (NEG) compared to its presence (p = 0.023); as well as when comparing NEG, D and ND mutations (p = .047). There was a trend for PTEN loss to negatively impact OS (p = .101) and PFS (p = .171). When Group II genes were considered, two: GPR124 (p = .035) and IL7R (p = .094) were predictive of OS; and 3 genes: TP53 (p = .028), CREBBP (p = .057) and GPR124 (p = .056) were predictive of PFS. The total number of mutated genes had no significant clinical correlation. No gene mutation significantly correlated with chemo-response. Conclusions: This study is the first to describe gene mutations, including TP53 and several novel genes, with significant clinical correlation to OS and PFS. We can expect that as our cohort grows, a full landscape of genes important to SCLC will emerge.
Abstract 4594: Involvement of receptors tyrosine kinase in the modulation of store-operated calcium entry
Authors: Noémie Emeriau.
Journal: Cancer Research (2016)

Abstract A multitude of studies show that alterations in Ca2+ signalling initiate or support the development of hallmarks of cancer. In particular, the role of store-operated Ca2+ entry (SOCE) in tumorigenesis and tumour progression has been subject to intense investigation. SOCE is the main mechanism by which external Ca2+ enters into the cell. It is initiated by depletion of ER Ca2+ stores and mediated by several proteins such as STIM1, an ER transmembrane protein sensing Ca2+ within the ER and ORAI1, a plasma membrane Ca2+ channel. We recently showed that SOC inhibition interfered with EGFR-dependent signalling in non-small cell lung carcinoma cells. In this study, we observed that STIM1 depletion reduced neuregulin-dependent proliferation of breast cancer cells. Since neuregulin binds to ErbB3 and/or ErbB4 and therefore activates ErbB2, this result prompted us to investigate whether ErbB proteins might modulate SOCE. We observed that lapatinib, a dual inhibitor of EGFR and ErbB2, dramatically inhibited SOCE. As expected, lapatinib also inhibited phosphorylation of EGFR, ErbB2 and downstream pathways of both receptors. Specific inhibition of EGFR by erlotinib or gefitinib had no effect on SOCE. In contrast, specific inhibition of ErbB2 by CP724714 mimicked the effects of lapatinib. We also investigated the role of downstream pathways of ErbB2 in the modulation of SOCE. Inhibition of the MAPK and the JAK-STAT pathways does not modify the amplitude of SOCE. Contrariwise, LY294002 and MK2206, two inhibitors of the PI3K pathway, dramatically reduced SOCE. Interestingly, in silico analysis showed that STIM1 might be phosphorylated by Akt. All these results suggest that SOCE is important in the proper function of ErbB2-dependent signalling. This raises the possibility to target molecular mediators of SOCE in order to interfere with the proliferation of cancer cells. Citation Format: Noémie Emeriau. Involvement of receptors tyrosine kinase in the modulation of store-operated calcium entry. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4594.
Replenishing $13bn Global Fund is “not a given”
Authors: Sophie Cousins
Journal: BMJ (2016)

Failure to fully provide funds to tackle HIV, including through the Global Fund to Fight AIDS, Tuberculosis, and Malaria, will prolong the epidemic and in many countries mean that it rebounds and grows, said a report by the Global Fund Advocates Network released at the 2016 International Aids Conference in Durban this week.

Although the world had made encouraging progress in tackling AIDS, the report predicted that if contributions to the Global Fund stalled, HIV infections and deaths from AIDS would be likely to rise. The report came as Canada prepared to host the Fifth Replenishment Conference of the Global Fund in September.

Mark Dybul, executive director of the …