tbuckley/cabot-search huggingface dataset:
Irinotecan (I), carboplatin (C), and radiotherapy (RT) followed by bevacizumab (B) in the treatment of limited-stage small cell lung cancer (SCLC): A phase II trial of the Minnie Pearl Cancer Research Network
Authors: E. L. Raefsky, D. R. Spigel, F. A. Greco, D. A. Yardley, J. E. Bradof, D. V. Woytowitz, M. T. Schreeder, W. H. Liggett, J. D. Zubkus, D. Petrone, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2005)

7050 Background: Preclinical studies have demonstrated VEGF expression in SCLC, a target that may predict response to treatment with anti-angiogenic agents such as B. Few trials have incorporated these agents into the treatment of SCLC, providing rationale for studying B in addition to chemoradiotherapy. Methods: The primary endpoints of this multicenter phase II study were to assess the safety and response rate (RR) of I/C/RT followed by B in patients (pts) with limited-stage SCLC. Treatment consisted of: C AUC=5 IV D1, I 50mg/m2 IV D1, 8 Q 21D for 4 cycles, and concurrent RT 1.8 Gy QD to a total of 61.2 Gy, beginning with the 3rd cycle. 3rd and 4th cycles were 28D each. Pts were restaged after 4 cycles. Pts without progression or undue toxicity received B 10 mg/kg IV Q 14D for 10 doses. Eligibility criteria included: measurable disease, ECOG PS 0–1, adequate organ function, <500mg/24 hour proteinuria, informed consent, and absence of active brain metastases, or hemoptysis. Results: Forty-one pts were enrolled between 08/03 and 09/04. The range of follow-up is 2–14 months. Baseline characteristics include: median age 66 years (42–78); male/female, 35%/65%; ECOG PS 0,1,2: 29%/66%/5%. Grade (G)3/4 non-hematologic toxicity included: hypertension (5%), diarrhea (11%), DVT (5%), vomiting (13%), and fatigue (11%). G3/4 hematologic toxicity included: neutropenia (37%), anemia (0%), and thrombocytopenia (16%). There were no treatment-related deaths, however, 2 pts came off study for dyspnea possibly related to treatment. Response data are available for 37 pts. Complete/partial RR were observed in 12 pts (32%)/18 pts (49%), respectively, for an overall RR of 81%. Eleven percent of pts had stable disease, and no pts have had disease progression (3 pts were unevaluable.) Six-month progression-free (PFS) and overall survival (OS) were 92% and 87%, respectively. One-year PFS and OS will be presented at ASCO. Conclusions: I/C/RT followed by B is a safe and well-tolerated regimen with acceptable RR in the treatment of limited-stage SCLC. One-and two-year PFS and OS will be important in estimating the impact of B in the treatment of SCLC. No significant financial relationships to disclose.
Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin's lymphoma treated with BEACOPPescalated alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group
Authors: Peter Borchmann, Heinz Haverkamp, Andreas Lohri, Ulrich Mey, Stefanie Kreissl, Richard Greil, Jana Markova, Michaela Feuring-Buske, Julia Meissner, Ulrich Dührsen, Helmut Ostermann, Ulrich Keller, Georg Maschmeyer, Georg Kuhnert, Markus Dietlein, Carsten Kobe, Hans Eich, Christian Baues, Harald Stein, Michael Fuchs, Volker Diehl, Andreas Engert
Journal: The Lancet Oncology (2017)
Phase I evaluation of tipifarnib in combination with low-dose Ara-C (LDAC) in high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML): Interim results
Authors: J. E. Cortes, E. J. Feldman, D. Douer, A. Raza, S. Fruchtman
Journal: Journal of Clinical Oncology (2007)

14014 Background: Tipifarnib (T) is a farnesyltransferase inhibitor with clinical activity in MDS and AML. LDAC has utility in the elderly with MDS/AML; hence its use in combination with the investigational agent T to improve outcomes is warranted. Methods: The primary objective of this ongoing phase I, dose finding, multicenter, open-label study was to determine the maximum tolerated dose (MTD) based on dose limiting toxicities (DLT) of T+LDAC observed during the first 28 day cycle. MDS (IPSS Int 1, 2 or High) and untreated AML pts (age =75y or =65y with preceding MDS) or relapsed/refractory AML (age &gt;18y) were included. Planned sample size was up to 57 pts with a traditional 3+3 dose escalation and a minimum of 3 pts enrolled per cohort. T (Dose Level 0) was administered initially at 200mg PO BID x 21 days in combination with LDAC 10mg SC BID x 10 days; both repeated every 28 days. Efficacy will be assessed by bone marrow and peripheral blood count studies. Results: 15 pts have been enrolled to date: 2 MDS (Int 1 n=1, High n=1) and 13 AML (7/13 pts with no previous therapy); all 15 pts were evaluable. Mean baseline characteristics for the entire cohort were: age 76.2y, 67% men, Hb 9.4 ± 0.9 g/dL, WBC 8.7 ± 11.3 x 10 3 /μL, platelets 96.8 ± 96.6 x 10 3 /μL. The observed DLT for T+LDAC was generalized rash seen at Dose Level 3. The MTD was therefore determined to be T 300mg and LDAC 15mg. The most common grade 3/4 adverse events were neutropenia, thrombocytopenia, anemia, and rash. Conclusions: These interim findings show the combination of T at 300mg PO BID x 21 days and LDAC at 15mg SC BID x 10 days to be the MTD in this study. Assessment for efficacy is ongoing. [Table: see text] No significant financial relationships to disclose.
A randomized controlled trial to evaluate laparoscopic versus open complete mesocolic excision (CME) for stage II, III colorectal cancer (CRC): First efficacy results from Japan Clinical Oncology Group Study JCOG0404.
Authors: Masafumi Inomata, Hiroshi Katayama, Junki Mizusawa, Masahiko Watanabe, Kenichi Sugihara, Fumio Konishi, Seiichiro Yamamoto, Shuji Saito, Shoichi Fujii, Yoshihisa Saida, Hirotoshi Hasegawa, Tsuyoshi Etoh, Yoshihiro Moriya, Seigo Kitano
Journal: Journal of Clinical Oncology (2015)

656 Background: The benefits of laparoscopic surgery (LAP) compared with open surgery (OP) have been suggested; however, the long-term survival of LAP for advanced CRC requiring CME is still unclear. We conducted a trial to confirm the non-inferiority of LAP to OP in terms of overall survival (OS). Favorable short-term complications and clinical benefits of LAP have already been demonstrated. Overall survival, the primary endpoint, and late post-operative complications are presented here. Methods: Only accredited surgeons from 30 Japanese institutions participated. Eligibility criteria included histologically proven CRC; tumor located in the cecum, ascending, sigmoid or rectosigmoid colon; T3 or deeper lesion without involvement of other organs; N0-2 and M0; tumor size =&lt;8 cm; age 20-75 years. Patients with pathological stage III received adjuvant chemotherapy with fluorouracil plus leucovorin. The planned sample size was 1,050 patients with a power of 80%, a one-sided alpha of 5% and the non-inferiority margin of the hazard ratio (HR) as 1.366. Results: A total of 1,057 patients were randomized (OP 528, LAP 529) between October 2004 and March 2009. Conversion to OP was needed for 29 patients in LAP arm. 5-year OS was 90.4% (95% CI: 87.5-92.6%) in OP, and 91.8% (89.1-93.8%) in LAP. The non-inferiority of laparoscopic CME in OS was not demonstrated (HR: 1.06 [90% CI: 0.79-1.41(&gt;1.366)], p=0.073). 5-year RFS was 79.7% (76.0-82.9) in OP and 79.3% (75.6-82.6) in LAP (HR: 1.07 [95%CI: 0.82-1.38]). Proportion of grade (G) 2-4 late complications was 22.6% (OP 12.5%, LAP 10.1%). Late complications (G2-G4) included constipations (OP 6.0%, LAP 4.4%), diarrhea (OP 2.9%, LAP 2.7%), paralytic ileus (OP 1.2%, LAP 1.7%), and bowel obstruction of small intestine (OP 3.1%, LAP 2.1%). Conclusions: The non-inferiority of laparoscopic CME in OS was not demonstrated for stage II, III CRC. However, since OS of both arms are almost identical and better than expected, laparoscopic CME is acceptable as a treatment option for stage II, III CRC. Clinical trial information: C000000105.
Role of histone deacetylase expression on regulating cancer stem cells in intrahepatic cholangiocarcinoma.
Authors: Y. Saito, M. Shimada, Y. Morine, S. Iwahashi, T. Utsunomiya, S. Imura, T. Ikemoto, H. Mori, J. Hanaoka
Journal: Journal of Clinical Oncology (2011)

219 Background: Histone deacetylase (HDAC) modulates gene expressions by chromatin remodeling during malignant transformation, and showed malignant behavior in intrahepatic cholangiocarcinoma (IHCC) (ASCO GI 2008). HDAC inhibitors have recently been found to repress the function of hypoxia inducible factors (HIF) through inducing hyperacetylation of histones. We also reported that the correlation between the expression of CD133, which was one of the cancer stem cell marker, and HIF-1α in IHCC (J Gastroenterol. 2010), and hypothesized that the cancer stem cell could be regulated by histone acetylation through the HIF-1α pathway. The aim of this study was to elucidate the potential mechanism of HDAC for the regulation of malignant behavior including the cancer stem cell in IHCC. Methods: Thirty-five patients with IHCC who underwent hepatic resection were evaluated. The expressions of HDAC1 (sc-6298 Santa Cruz Biotechnology, USA), HIF-1α (NB100-105 Novus Biologicals, USA) and CD133 (Ab27699 Abcam Inc, UK) were determined immunohistochemically, and the patients were divided into two groups: HDAC1 positive group (n=21); and negative group (n=14). Clinicopathological variables including HIF-1α and CD133 expressions were analyzed according to these expressions. Results: The HDAC1 expression correlated significantly with higher stage, lymph node metastasis, and vascular invasion. The prognosis in the HDAC1 positive group was poorer than in the HDAC1 negative group (5-year survival: 77.9% vs. 7.9%, p=0.001). In the multivariate analysis, HDAC1 positive expression was identified as the only independent prognostic factor for disease free survival (Hazard Ratio: 7.194, p=0.0018). There was a significant correlation between HDAC1 expression and HIF-1α expression (p=0.007), and also between HIF-1α expression and CD133 expression (p=0.10). Furthermore, co-expressions of these markers in same cancer cells were proven by immunofluorescent staining in the serial section. Conclusions: The findings suggested that histone acetylation regulated cancer stem cell through the HIF-1α pathway; therefore, HDAC1 might be a possible promising molecular target in IHCC. No significant financial relationships to disclose.
Feasibility study of neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for clinical stage II/III esophageal squamous cell carcinoma.
Authors: K. Kato, H. Hara, H. Daiko, H. Igaki, Y. Hamamoto, M. Nagase, S. Kadowaki, M. Tahara
Journal: Journal of Clinical Oncology (2011)

95 Background: In JCOG 9907, neoadjuvant chemotherapy with cisplatin and 5-fluorouracil (CF) improved overall survival without additional serious adverse events in treating stage II/III esophageal squamous cell carcinoma (ESCC). However, ESCC patient survival remains unsatisfactory. We conducted a feasibility study of neoadjuvant chemotherapy with docetaxel plus CF (DCF) for clinical stage II/III ESCC. Methods: Eligibility criteria included clinical stage II/III (non-T4) ESCC, PS 0–1, and age 20–70 years. Chemotherapy consisted of a 1-h infusion of docetaxel at 70 mg/m 2 and 2-h infusion of cisplatin at 70 mg/m 2 (day 1), and continuous infusion of 5-FU 750 mg/m 2 (days 1 to 5). Antibiotic prophylaxis on days 5 to 15 was mandatory. This regimen was repeated every 3 weeks (maximum 3 cycles) until unacceptable toxicity, patient refusal, or disease progression was observed. After chemotherapy completion, transthoracic esophagectomy with extended (&gt; D2) lymphadenectomy was performed. The primary endpoint was the completion rate of protocol treatment. Results: From July 2009 to Feb 2010, 34 patients were enrolled, including 2 ineligibles. The 32 eligibles had a median age of 61 (range 36–70; male/female: 30/2), with PS0/1 of 20/12 and cStage IIA/IIB/III of 6/8/18. During chemotherapy, the most common grade-3 or -4 toxicities were neutropenia (88%), febrile neutropenia (3%), anorexia (9%), and stomatitis (6%). Thirty-one (97%) patients underwent surgery. The protocol completion rate was 87.5% (28/32). No treatment-related death was observed, and the operative morbidity incidence was comparable to those in previous studies. According to RECIST, the overall response rate was 61.5% after DCF completion. Primary-lesion pathological complete response was achieved in 26% of patients (8/31) who underwent esophagectomy. Conclusions: Neoadjuvant DCF was well tolerated. Although these data are preliminary, the protocol is highly promising and warrants further investigation. No significant financial relationships to disclose.
MET overexpression as a hallmark of the epithelial-mesenchymal transition (EMT) phenotype in colorectal cancer.
Authors: Kanwal Pratap Singh Raghav, Hesham M. Amin, Wenting Wang, Ganiraju C. Manyam, Bradley Broom, Cathy Eng, Michael J. Overman, Scott Kopetz
Journal: Journal of Clinical Oncology (2013)

3529 Background: Epithelial-mesenchymal transition (EMT) has been identified as a dominant molecular subtype of colorectal cancer (CRC). This EMT phenotype as recognized by complex gene signatures is prognostic and associated with chemoresistance, but a biomarker for EMT suitable for clinical utilization has not yet been validated. The purpose of this study was to compare MET protein expression with protein/gene expression of EMT markers and to evaluate its impact on overall survival (OS). Methods: We performed an exploratory analysis of 139 untreated primary CRC samples using data from The Cancer Genome Atlas. Protein and gene expressions were measured using reverse-phase protein array (RPPA) and RNA-sequencing, respectively. MET high/overexpressed group was defined by protein level in the highest quartile. Mann-Whitney U-test and Spearman rank correlation was used to determine association between MET protein expression and protein/gene expression of EMT markers and EMT gene signature scores. Regression tree method and Kaplan-Meier estimates were used to assess overall survival (OS). Results: The MET protein distribution is right skewed, demonstrating a unique population of MET high expressing tumors (P &lt; 0.01). Colon tumors had higher MET protein levels compared to rectal tumors (P &lt; 0.01). MET overexpression was associated with decreased OS (HR 2.92; 95% CI: 1.45 - 5.92). MET protein expression correlated strongly with protein expressions of SLUG (transcription factor for EMT) (r = 0.6) and ERCC1 (a marker for oxaliplatin chemo-resistance) (r = 0.6) (P &lt; 0.01). Higher MET protein levels were associated with higher gene expression of 28 EMT markers including AXL, VIM, ZEB1, ZEB2, FGF1, TGFB1I1 and MMP11 (P &lt; 0.05). Higher MET protein levels were also associated with higher gene scores derived from three published EMT gene signatures (P &lt; 0.05). MET protein expression did not correlate with MET gene expression (r = 0.16). Conclusions: Increased MET protein expression strongly correlates with a molecular EMT phenotype and poor survival in patients with CRC. MET protein expression may be used as a surrogate biomarker to represent and select for this unique molecular subset of CRC driven by EMT biology.
Generation and Characterization of a Novel CD19-CherryLuciferase (CD19CL) Mouse Model: A New Fluorescent/Bioluminescent Model for the Study of B-Cell Development and Lymphomagenesis
Authors: Luigi Scotto, Marianna Kruithof de Julio, Luca Paoluzzi, Matko Kalac, Enrica Marchi, Jairo Baquero Buitrago, Owen A. O'Connor
Journal: Blood (2010)
Role of C/EBP homologous protein and endoplasmic reticulum stress in asthma exacerbation by regulating the IL-4/signal transducer and activator of transcription 6/transcription factor EC/IL-4 receptor α positive feedback loop in M2 macrophages
Authors: Yi Wang, Jianghui Zhu, Lei Zhang, Zhijun Zhang, Long He, Yong Mou, Yanhan Deng, Yong Cao, Ping Yang, Yunchao Su, Jianping Zhao, Shu Zhang, Qilin Yu, Jifa Hu, Zhishui Chen, Qin Ning, Xudong Xiang, Yongjian Xu, Cong-Yi Wang, Weining Xiong
Journal: Journal of Allergy and Clinical Immunology (2017)
Brain metastases in patients with urothelial carcinoma.
Authors: Helen Jane Boyle, Emile Lavergne, Jean Pierre Droz, Nathalie Bonnin, Aude Flechon
Journal: Journal of Clinical Oncology (2012)

e15009 Background: Muscle invasive urothelial cancers are infrequent. Patients (pts) with metastatic disease have poor prognosis. Brain metastases (BM) are rare. The aim of this retrospective study is to analyse the characteristics, the treatment and the evolution of patients with BM treated in a single centre. Methods: Thirty pts with BM were identified among the 1591 pts with urothelial carcinoma seen at the Centre Léon Bérard, between 1994 and 2011. The study population was described, overall survival (OS) from diagnosis of BM was estimated by Kaplan-Meier method and prognostic factors were explored using a Cox model. Results: Twenty seven pts in our series were male. Median age at initial diagnosis was 60 years (range: 33.9-78.9 years). Twenty two pts had primary bladder tumours and 8 upper urinary tract tumours. Twenty four pts underwent surgery for their primary lesion, 2 received chemoradiotherapy and 4 did not receive any radical local treatment. Six pts had metastatic disease at initial presentation: 3 were operated on. Median delay between initial diagnosis and BM was 16.6 months (range: 0-56.4 months), 3 patients had BM at initial presentation. Median time between first metastases and BM was 10 months (range=0-52 months). Eleven patients developed BM as one of the first sites of metastases. BM were symptomatic in 28 pts: specific neurological symptoms (n=25), headaches (n=6), epilepsy (n=2). For the 2 other pts, they were discovered on a systematic brain MRI. Eighteen pts had cerebral metastases only, 5 pts had cerebellar metastases only, 6 had both; the last patient had cerebral, cerebellar and meningeal involvement. Half of the pts had only 1 brain lesion. Five pts were operated on: 4 received postoperative radiotherapy; 19 patients were given radiotherapy alone and 6 did not get any local therapy. In this series, median OS from diagnosis of BM was 3.4 months (IC95% [2.2-10.3]). Only the administration of chemotherapy after the diagnosis of BM was significantly associated with OS; probably because only fit enough patients were offered treatment. Conclusions: Prognosis of patients with urothelial carcinoma and BM is poor; however some patients have long survivals. Treatment is not codified as there is little data in the literature.
Prognostic significance of mortalin expresion in gastric adenocarcinoma with wild-type p53.
Authors: E. Oki, K. Ando, H. Saeki, T. Ohga, Y. Kakeji, S. Tsujitani, T. Kusumoto, Y. Maehara
Journal: Journal of Clinical Oncology (2011)

e14662 Background: Mortalin is a heat non-inducible member of the heat shock protein 70 family that is expressed in various stress responses such as glucose deprivation, low-dose ionizing radiation, and caloric restriction. Mortalin and p53 form a complex in the cytoplasm or in the centrosome, which compromises the p53 activity, and thus prevents apoptosis under stress conditions. Methods: This study included 182 unselected Japanese patients with primary gastric cancer. The expression of mortalin and aberrant p53 was investigated by immunohistochemical staining. In addition, the human fibroblast cell line MRC-5 and the gastric cancer cell line MKN-74, which has a mutation in the TP53 gene, were grown under normal or hypoxic conditions, and changes in localization of mortalin and p53 were examined. Results: Mortalin-positive and aberrant-p53-positive samples were found in 75.2% and 62.6% of cases, respectively. The Mortalin and aberrant p53 expression was associated with tumor invasion and lymph node and liver metastases. The expression of aberrant p53 and mortalin was significantly correlated in gastric cancer samples, but the proteins were not co-localized. The mortalin expression affected the prognosis of gastric cancer with the expression of normal p53. Mortalin-positive tumors with expression of normal p53 had significantly worse prognosis in comparison to mortalin-negative tumors. With multivariate analysis, mortalin expression appeared to be an independent prognostic factor in gastric cancer with expression of normal p53 (p = 0.0174). We investigated expression of mortalin and p53 in cell lines under normal or hypoxic conditions. Mortalin and p53 co-located in the perinuclear region under hypoxic conditions in the p53 wild-type MRC-5 cell line; however, they were not co-localized under hypoxic conditions in the p53 mutant gastric cancer cell line. Conclusions: Mortalin expression seems to be important in gastric cancer, especially in tumors with expression of normal p53. Further investigation of mortalin and aberrant p53 expression is necessary. Targeting mortalin might be a promising treatment for the p53 wild-type patient.
Barriers to repeat mammography screening: Perspectives of minority women
Authors: B. Moy, E. R. Park, S. Feibelmann, S. Chiang, J. S. Weissman
Journal: Journal of Clinical Oncology (2005)

6051 Background: Women of minority races have lower levels of mammography screening and have lower mammography return rates compared to Caucasians. To better understand this problem, we conducted a study of African American, Hispanic, and Asian women’s experiences with mammography. Methods: Six focus groups were conducted with a total of 49 women (19 Asian, 16 African American, and 14 Hispanic) recruited from community medical clinics in Boston. Eligible women had at least one prior mammogram and no personal history of cancer. Focus groups were guided by the attitude-social influence-efficacy model. Cultural barriers to repeat mammography were explored. Discussions were recorded and transcribed, and thematic content analyses were performed. Results: All groups expressed that older generations considered breast health a taboo topic. African American and Hispanic women felt that lack of insurance was not a barrier to mammography since they were savvy about free care options. A prominent reason that African Americans avoided mammograms was a fatalistic belief that a breast cancer diagnosis would inevitably lead to death. African Americans felt that ongoing cancer screening was not a priority because other diseases, such as HIV, were of greater concern. African Americans also felt that dominant social issues, such as drug and domestic abuse, made adherence to preventive health care less important. In contrast, Asians felt that mammogram return rates were poor because appointments took time away from work. Asian and Hispanic women identified discourteous behavior by hospital staff as a barrier. Most Asians were bothered by the staff’s insensitivity to their embarrassment of having to undress for mammograms. Many Hispanics were bothered by a language barrier and perceived indifference of the hospital staff. Conclusions: Cultural barriers to repeat mammography appear to vary among different racial groups. Interventions to improve screening among minority populations may be more successful if they address group-specific concerns. No significant financial relationships to disclose.