tbuckley/cabot-search huggingface dataset:
Evaluation of ALDH1-A1 as a biomarker for metastasis of head and neck cancer.
Authors: Z. G. Chen, S. Nannapaneni, S. Muller, N. F. Saba, M. Tighiouart, L. Pan, D. M. Shin
Journal: Journal of Clinical Oncology (2010)

5549 Background: Aldehyde dehydrogenase (ALDH) families are cytosolic isoenzymes that are responsible for conversion of acetaldehyde to acetic acid. ALDH1-A1 is suggested to be associated with premalignant lesions of the head and neck tissues. To date, correlation of ALDH1-A1 expression with metastasis in squamous cell carcinoma of the head and neck (HNSCC) has not been reported. Methods: We examined ALDH1-A1 expression in HNSCC surgical specimens and compared ALDH1-A1 expression in HNSCC patients without lymph node metastasis (LNM) to the patients with LNM. We further examined ALDH1-A1 mRNA level using RT-PCR in 8 HNSCC cell lines, 4 from primary tumors and 4 from their paired LNM. Immunoblotting analysis was used to confirm ALDH1-A1 protein expression in these cell lines. A total of 180 patients with HNSCC were examined: 93 cases from patients who had no LNM at diagnosis and within 2-year follow up, and 87 patients who exhibited LNM. No patients received chemo- and/or radiation therapy prior to surgical treatment. Formalin-fixed paraffin embedded sections were stained with goat polyclonal ALDH1-A1 antibody at a dilution of 1:200 using standard immunohistological procedures. The sections were analyzed by a pathologist and scored according to the following scheme: 1+: <5 %; 2+: 5-25%; 3+: 26-50%; 4+: >50% positive cells staining. Results: Statistically there was a significant increase in ALDH1-A1 expression in primary tumors with LNM compared to the primary tumors without LNM (2.12 vs. 1.26, p<.0003). The corresponding LNM also had higher ALDH1-A1 expression compared to tumors without LNM (2.19 vs. 1.26, p<.0001). Although the LNM had higher ALDH1-A1 expression than the corresponding primary tumor, the difference between these two groups was not significant (2.19 vs. 2.12). Further study on HNSCC cell lines showed that ALDH1-A1 mRNAs were expressed in 6 of 8 HNSCC cell lines and higher in 2 cell lines from LNM than their primary tumor counterparts. The expression pattern of ALDH1-A1 protein is consistent with that of the mRNA, suggesting that ALDHI-A1 is primarily regulated at transcription level. Conclusions: We have shown that ALDH1-A1 is expressed in HNSCC and its expression pattern implies that ALDH1-A1 might be a marker for metastatic HNSCC. No significant financial relationships to disclose.
AB0270 Can Alkaline Phosphatase and Gamma-Glutamyl Transferase be Used as Inflammatory Markers in Patients with Rheumatoid Arthritis?
Authors: B. Kısacık, I.H. Türkbeyler, O. Zengin, M.S. Dağ, Y. Pehlivan, Z.A. Öztürk, G. Kimyon, A.M. Onat
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) have been previously investigated in patients with rheumatoid arthritis (RA); however their potential role on diseases activity has not been studied yet (1-2). <h3>Objectives</h3> Presented study aimed to investigate the correlation of ALP and GGT with disease activity (as assessed by DAS28) and acute phase reactants in patients with RA. <h3>Methods</h3> In total 81 newly diagnosed RA patients (male/female: 70/11), who fulfilled the 1987 American College of Rheumatology (ACR) classification criteria, as well as 32 healthy controls (male/female: 26/6) enrolled into study. Disease activity was assessed by DAS28. Demographic data, levels of ALP, GGT, and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and DAS28 scores were obtained from the patient files when first diagnosed and compared with each other. <h3>Results</h3> Comparing RA patients with the control group, the ESR, and the levels of CRP, ALP and GGT were found higher in the RA group as compared to the control group. But only ESR and CRP levels were found statistical significance higher (p&lt;0,05). Moreover, ALP, GGT levels were found to be positively correlated with ESR, and CRP levels (p&lt;0,05). <h3>Conclusions</h3> In this study we found that levels of ALP and GGT were correlated with ESR and CRP levels although DAS28 disease activity criteria wasn9t found to be positively correlated with ALP and GGT levels. In RA patients levels of ALP and GGT may be used as disease activity indicators like ESR and CRP. However, more comprehensive studies are needed to make definite correlations between DAS 28, disease activity criteria, and levels of ALP and GGT. <h3>References</h3> Richardson C, Emery P. Laboratory markers of disease activity. J Rheumatol (suppl 44) 1996; 23: 23-30. Pepys MB. Rheumatoid arthritis: The role of acute phase proteins. Br J Rheumatol 32 1993; (suppl 3): 1-2. <h3>Disclosure of Interest</h3> None declared
Emergency laparotomy for spontaneous intestinal and colonic perforations in cancer patients receiving corticosteroids and chemotherapy.
Authors: M H Torosian, A D Turnbull
Journal: Journal of Clinical Oncology (1988)

Thirty patients with lymphoma (12), leukemia (two), myeloma (one), or metastatic solid tumors (15) were explored for 31 episodes of spontaneous intestinal perforation during an 11-year period at Memorial Sloan-Kettering Cancer Center. Twenty-three patients (76.6%) were receiving corticosteroids alone or in combination with chemotherapy and seven patients (23.4%) were receiving chemotherapy alone at the time of perforation. Fourteen perforations (45%) occurred in the small intestine and 17 perforations (55%) occurred in the colon. Malignancy was histologically demonstrated at the site of perforation in 16 patients (52%). Twenty major postoperative complications occurred in 15 patients (50%) and the operative mortality rate was 53%. Factors such as age, sex, duration or type of symptoms, site of perforation, malignancy at the site of perforation, peripheral leukocyte count, and serum albumin and total protein levels were not significantly related to patient survival. Early diagnosis and aggressive surgical intervention is essential to improve survival following intestinal perforation in this high-risk population.
Genoidentical PBSCT with reduced intensity conditioning compared to autologous PBSCT for old patients with acute leukemia: An EBMT matched pair analysis.
Authors: V. Rocha, Augustin Ferrant, M Labopin, JM Boiron, F. Garban, E Polge, E. Gluckman, L. Fouillard, F. Frassoni
Journal: Blood (2002)
Bevacizumab in hepatocellular carcinoma in patients without metastasis and without invasion of the portal vein
Authors: J. D. Schwartz, M. Schwartz, J. Goldman, D. Lehrer, D. Coll, M. Kinkabwala, S. Wadler
Journal: Journal of Clinical Oncology (2004)

4088 Background: Hepatocellular Carcinoma (HCC) is a highly vascular tumor in which angiogenic cytokines (including VEGF) likely contribute to pathogenesis. Bevacizumab (anti-VEGF) has been shown to delay progression in colorectal and renal cancers. VEGF-inhibition has not been previously attempted in cirrhosis and bevacizumab has been associated with bleeding complications in non-HCC patients. Methods: Hence, we enrolled a limited cohort of patients with unresectable HCC to treatment with bevacizumab at 5mg/kg every 14 days to assess safety. Inclusion criteria were BR < 3.0mg/dl, transaminases < 5X upper limit of normal, platelets > 75K and prothrombin time within 4 seconds of normal. Additional criteria included no history of gastrointestinal bleeding, myocardial infarction stroke, or condition requiring ongoing antiplatelet or antithrombotic therapy. Results: An initial safety assessment indicates that 5 of 6 patients treated for at least 8 weeks tolerated bevacizumab with minimal toxicity (grade 1 neutropenia, acneform rash, proteinuria, fatigue and vocal changes; grade 2 thrombocytopenia). One patient had a fatal esophageal variceal bleed which was possibly related to therapy, although concomitant HCC progression likely contributed to this event. The protocol has been modified to more readily identify and treat esophageal varices prior to enrollment. An additional patient died of fulminant peritonitis and sepsis within five days of receiving initial bevacizumab; this has been determined to be unrelated to therapy. For the 5 patients evaluable for efficacy, there has been 1 PR, 3 SD (with eventual progression at 6.4, 7.2 and 7.6 months). Conclusions: Preliminary assessment indicates that bevacizumab is safe and potentially efficacious in localized HCC in patients with adequate liver function. Because of safety concerns, an additional 6 patients will be enrolled at 5mg/kg before safety/efficacy is evaluated at 10mg/kg. Additional data regarding tumor necrosis and treatment related changes in tumor perfusion will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck; Pfizer
The Chinese subgroup from a randomized phase III study of lapatinib in combination with weekly paclitaxel versus weekly paclitaxel alone as second-line treatment of HER2-amplified advanced gastric cancer (AGC) in Asian countries.
Authors: Guo-ping Sun, Yan Sun, Rui-hua Xu, Jian-Ming Xu, Jin Li, Jin-Wan Wang, Shukui Qin, Ji Feng Feng, Yi Ba, Lin Shen, Yu-Xian Bai, Yihong Sun, Hongming Pan, Ying Cheng, Shiying Yu, Haijun Zhong, Li Bai, Rongcheng Luo, Mikiro Kobayashi, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2013)

4109 Background: TyTAN is a randomized phase III study to evaluate lapatinib (L) plus paclitaxel (P) in pretreated HER2 amplified (HER2+) advanced gastric cancer (AGC). The disease characteristics and GC treatment pattern differed in Japan and in China, so a subgroup analysis was done for subjects recruited in mainland China. Methods: AGC subjects with prior 5-FU and/or cisplatin and HER2 amplification by fluorescence in situ hybridization (FISH) in tumor tissue were randomized 1:1 to L (1500mg QD) and P (80mg/m 2 , Day 1, 8, 15 q4w) or P alone (80mg/m 2 , Day 1, 8, 15 q4w). 1st endpoint was overall survival (OS). 2nd endpoints included progression free survival (PFS), overall response rate (ORR) and safety. A total of 95 subjects recruited from mainland China. Results: TyTAN was not significant in OS (HR0.84), but 2 months OS improvement was observed in L+P arm. The results from Chinese subgroup are shown in the Table. The most common adverse events in Chinese subjects were similar as in whole population (neutropenia, diarrhea, rash, leukopenia, anemia, fatigue). Compare to the overall results, less Chinese subjects reported nausea and vomiting. Conclusions: This analysis showed that there were clear regional differences as observed between subjects in China and Japan. The addition of L to P was associated with a clinically meaningful benefit in subjects recruited from mainland China. These data warrants further prospective evaluations on the impact of regional differences in the outcome of HER+ GC in East Asian patients. Clinical trial information: NCT00486954. [Table: see text]
OSAD 93: A multicentric prospective phase II study of preoperative high dose Ifosfamide and CDDP in adult patients with non metastatic osteosarcoma
Authors: P. Biron, F. Rolland, A. Thyss, M. C. Baranzelli, M. Rios, H. Roché, B. Bui, D. Perol, J. Y. Blay
Journal: Journal of Clinical Oncology (2004)

9019 Objectives: Based on a previous monocentric phase II trial with neoadjuvant ifosfamide CDDP based regimen in adults, a multicentric phase II study of neoadjuvant chemotherapy for osteosarcoma of patients over 16 years was initiated in 1993 in the French Sarcoma Group. Methods: Four preoperative courses of ifosfamide 9g/m2 in 3 days and CDDP 100mg/m2 on day 4 (SHOC) were given, followed by local treatment. Post operative chemotherapy was adapted according to pathological response, doxorubicin (60mg/m2) being added (HOCA regimen) in patients with tumors >10% of viable tumor cells. Pathological response rate) was the principal objective of the study. Results:Between January 94 and June 1998, 63 pts were included, 14 females, 49 males, with a median age of 27 (range: 16–63). Primary tumors were femur (39%), tibia (12%), humerus (10%), flat bones (28%). Grade 3 and 4 neutropenia, febrile neutropenia, thrombopenia and rehospitalisation occured after 58%, 17%,17% and 22% of courses of SHOC and 76%, 28%,47%, 47% of the courses of HOCA. Respectively 13%, 19%, 24%, 32% and 12% of patients had grade 4, 3, 2, 1, and non evaluable pathological response to preoperative chemotherapy. Good pathological response was observed in 20 (31%) of included patients. With a 68 months median follow-up, overall and progression-free survival at 5 year are 54% and 47% both (PFS 72% and 35%, and OS 81% and 50% respectively for good and poor responders) Conclusions: In adult patients, preoperative high dose ifosfamide and CDDP (SHOC) regimen yields response rate and survival comparable to that achieved with doxorubicin containing regimen. No significant financial relationships to disclose.
High dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) in adults with relapsed CNS embryonal tumors
Authors: P. Gill, E. Galanis, J. Buckner, T. Christianson, P. Anderson, S. Ansell, M. Litzow
Journal: Journal of Clinical Oncology (2005)

1525 Background: Embryonal CNS tumors are rare in adults. Recurrent disease has poor outcomes. HDC with ASCT shows promising results in children. There is limited data regarding its role in adults. We evaluated patients treated with HDC with ASCT and compared outcomes to those who received conventional dose chemotherapy. Methods: We reviewed medical records of 25 adults (≥ 18 yrs) treated at our institution for relapsed CNS embryonal tumors between 1976 and 2004. We compared HDC with ASCT (conditioning regimen thiotepa + carmustine, thiotepa + carboplatin or carboplatin + etoposide + cyclophosphamide; n=10) to conventional dose chemotherapy (nitrosourea, cis-platin or both; n=13). Results: In the ASCT group median age was 32.5 yrs. 8 had medulloblastoma, 2 cerebral neuroblastoma. 8 transplanted at 1st relapse, 2 at 2nd relapse. In the conventional dose chemotherapy group median age was 26 yrs. 11 patients had medulloblastoma, 2 cerebral neuroblastoma. Cox proportional hazards models and Kaplan-Meier analysis were used to estimate survival after HDC with ASCT to the non-ASCT group. In the non-ASCT group there were no long-term survivors, 13 patients died after 1st relapse. In the ASCT group 5 patients died after 1st relapse and 5 are alive (4 without progression) at last follow up, median follow up 2.9 yrs. There were no treatment-related deaths in either group. Transplant was associated with increased survival, p=0.044. The hazard ratio for the non-ASCT group was 3.12 (95% CI, 1.03–9.43). Results were similar after adjusting for tumor type, metastases at 1st relapse or removing the 2 patients who received ASCT after 2nd relapse. The non -ASCT group had a median time to progression (TTP) and a median survival of 0.58 and 2.00 yrs, respectively. The ASCT group had a median TTP and median survival of 1.25 and 3.47 yrs, respectively. When restricted to patients receiving ASCT after first relapse, the median TTP was 2.5 yrs and median survival was 3.03 yrs. Conclusions: Improvement in survival with HDC with ASCT supports consideration of its use in adults with relapsed CNS embryonal tumors. No significant financial relationships to disclose.
Pediatric Preclinical Testing Program (PPTP) testing of the CENP-E inhibitor GSK923295A
Authors: M. A. Smith, C. L. Morton, H. Carol, R. G. Gorlick, M. H. Kang, S. T. Keir, E. A. Kolb, R. B. Lock, J. M. Maris, P. J. Houghton
Journal: Journal of Clinical Oncology (2009)

10015 Background: GSK923295A is a small molecule inhibitor of centromere-associated protein E (CENP-E), a mitotic kinesin that is required for metaphase chromosome alignment and integration of mitotic spindle mechanics with mitotic checkpoint signaling. An initial phase I clinical trial in adults is ongoing. Methods: The PPTP includes a molecularly characterized in vitro panel of cell lines (n = 27) and in vivo panel of xenografts (n = 60) representing most of the common types of childhood solid tumors and childhood acute lymphoblastic leukemia (ALL). GSK923295A was tested in vitro at concentrations from 1.0 nM to 10.0 μM (96 hour exposure) and was tested in vivo using a daily × 3 for 2 weeks schedule, repeated at day 21. GSK923295A was administered IP at a dose of 125 mg/kg. Three measures of antitumor activity were used: 1) an objective response measure modeled after the clinical setting; 2) a time to event measure based on the median event-free survival (EFS); and 3) a treated to control (T/C) tumor volume measure. Results: GSK923295A demonstrated potent in vitro activity against the PPTP cell line panel with a median IC50 of 27 nM (range 12 nM to &gt; 10 μM). 35 of 37 solid tumor xenograft models were evaluable. GSK923295A induced significant differences in EFS distribution compared to controls in 32 of 35 evaluable models. Objective responses were noted in 13 of 35 xenografts, including 9 with maintained complete responses (MCR), 3 with complete response (CR), and 1 with partial response (PR). Three of 5 Ewing sarcoma xenografts achieved MCR or CR, as did 2 of 3 rhabdoid tumor, and 2 of 5 rhabdomyosarcoma models. For the neuroblastoma panel, the best response was progressive disease (PD) with growth delay compared to controls (PD2 response), which was observed in 5 of 6 xenografts. GSK923295A showed activity against the ALL panel, but unexplained toxicity (generally on or after day 21) precluded formal analysis. Conclusions: GSK923295A has substantial in vitro and in vivo activity against the PPTP's preclinical models. The observed high level of preclinical activity for GSK923295A will need to be evaluated in the context of systemic exposures achieved in the xenograft models and those achievable in humans at tolerable doses. (Supported by NCI NO1CM42216) [Table: see text]
A phase II study of lapatinib (GW572016) in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN)
Authors: O. O. Abidoye, E. E. Cohen, S. J. Wong, M. F. Kozloff, S. R. Nattam, K. M. Stenson, E. A. Blair, S. Day, J. E. Dancey, E. E. Vokes
Journal: Journal of Clinical Oncology (2006)

5568 Background: Epidermal growth factor receptor (EGFR) inhibitors have demonstrated reproducible activity in patients with R/M SCCHN. HER2 is the preferred dimerization partner for EGFR. Lapatinib is a dual EGFR and HER2 kinase inhibitor that has demonstrated promising preclinical activity in SCCHN models. Methods: This phase II multi-institutional study enrolls patients with R/M SCCHN into 2 cohorts: those without prior exposure to an EGFR inhibitor (arm A) and those with prior exposure to an EGFR inhibitor (arm B). All subjects were treated with lapatinib 1500mg OD. Primary endpoints were response rate (arm A) and progression-free survival (arm B). Results: 42 subjects have been enrolled (27 arm A, 15 arm B; 35 male, 7 female, median age 60 years). Toxicity was generally mild without any dose reductions or patient withdrawal due to adverse effects. Diarrhea was the most frequent toxicity occurring in 40% of patients. Other toxicities observed included fatigue (21%), rash (21%) and nausea (14%). 2 patients experienced grade 3 toxicity (1 diarrhea, 1 emesis). 1 patient had a reduction in left ventricular ejection fraction (60% to 40%) which was asymptomatic and recovered to baseline upon discontinuation of lapatinib. No objective responses were observed in either arm. In an intent-to-treat analysis stable disease was the best response observed in 37% of arm A and 20% of arm B subjects. Median PFS was 1.6 months in arm A and 1.7 months in arm B. Conclusions: Lapatinib as a single agent in R/M SCCHN, although well tolerated, appears to have little activity in either EGFR inhibitor naïve or refractory subjects. No significant financial relationships to disclose.
Randomized phase II trial of three dosing schedules of nanoparticle albumin-bound paclitaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer: An initial interim safety report
Authors: A. K. Conlin, A. D. Seidman, M. E. Moynahan, T. Traina, J. R. Mace, E. Meiri, A. Bach, C. Edwards, C. A. Hudis
Journal: Journal of Clinical Oncology (2007)

1104 Background: Nanoparticle paclitaxel (NP) at 260mg/m 2 every 3 weeks (q3wk) is more effective than standard paclitaxel (P) (Gradishar et al, JCO 2005). Weekly, uninterrupted administration of P is superior to q3wk P in MBC (Seidman et al, Proc ASCO 2004). When added to weekly P as 1 st -line therapy for MBC, bevacizumab (B) improves response rate and progression-free survival (Miller et al, Proc ASCO 2005). We initiated a randomized phase II trial of NP given at 260mg/m 2 q3wk (arm A) vs. 260mg/m 2 q2wk with filgrastim (arm B) vs. 130mg/m 2 weekly, all with B, as 1st-line therapy for patients (pts) with HER2- MBC. Methods: 66 of planned 225 pts have enrolled. After 31 pts had been randomized and treated, investigators concerned about possible differential neurotoxicity requested this early interim safety analysis. Median age is 54 (range 40–78). 83% are post-menopausal and 100% have visceral dominant disease. 68% had prior adjuvant or neo-adjuvant chemotherapy; 35% with taxanes. Results: With 170 cycles delivered (median: 4, range 1–15) 10 dose reductions have been necessary for NP (1 in A, 5 in B, 4 in C). No hypersensitivity reactions or dose interruptions have occurred for NP; 3 doses of B have been held due to hypertension. Significant preliminary antitumor activity has been noted in all arms. One grade 4 toxicity occurred in arm C, hyperglycemia. 15 grade 3 toxicities have been reported across all arms. Pts on arm A have experienced 3 grade 3 toxicities (30%): fatigue, neutropenia, and arthralgia with no grade 3 neurotoxicity. Pts on arm B have had 7 grade 3 toxicities (58%) with 3 pts experiencing grade 3 sensory neuropathy (25%) and others experiencing fatigue, neutropenia, anemia, esophagitis, dyspnea, and ataxia. 5 arm C pts experienced grade 3 toxicities (56%) including diarrhea, dehydration, mucositis, neutropenia, hypokalemia; 2 pts have had grade 3 sensory neuropathy (22%). Conclusions: This early safety analysis does not detect any statistically or clinically significant differences in grade 3 toxicity and all arms continue to accrue. The next protocol-specified safety analysis is expected in early 2007, with mature safety data for 60 pts. Updated results will be presented. [Table: see text]