tbuckley/cabot-search huggingface dataset:
A phase I study of NY-ESO-1 overlapping peptides with or without incomplete Freund's adjuvant and poly-ICLCL vaccination of ovarian cancer patients in second or third clinical remission.
Authors: C. S. Magid Diefenbach, P. Sabbatini, M. L. Hensley, J. A. Konner, W. P. Tew, G. Ritter, A. Jungbluth, L. S. Pan, L. J. Old, S. Gnjatic
Journal: Journal of Clinical Oncology (2010)

TPS174 Background: This is a first-in-human phase I study of NY-ESO-1-overlapping peptides (OLP-4)in conjunction with incomplete Freund's adjuvant (IFA) and the immunomodulator Poly-ICLC, a toll-like-receptor 3 (TLR-3) agonist in patients with epithelial ovarian cancer (EOC). The primary endpoint is safety and the secondary endpoint is immunogenicity. Nearly 70% of patients with advanced EOC who achieve complete clinical remission (cCR) after initial therapy relapse. Immune activation is associated with improved clinical outcome. NY-ESO-1 is strongly immunogenic, and highly expressed in advanced EOC, but in normal tissues expression is restricted to gonads. In a previous phase I trial of NY-ESO-1b peptide and IFA vaccination of EOC patients we demonstrated low toxicity and immune stimulation. The novel OLP-4 construct contains four 30-32mer NY-ESO-1 peptides overlapping by 10 amino acids, covering residues 79-173 including 90% of T cell epitopes, representing the most immunogenic regions, as well as many undefined epitopes and avoiding the limitation of patient eligibility by specific HLA restriction alleles. TLR binding activates adaptive immunity, stimulating antitumor CD8+ T cells. Poly-ICLC has been tested as a single agent in cancer, and as a dendritic cell vaccine adjuvant. Methods: Patients with EOC, in second or third cCR, KPS≥70, and adequate organ function were eligible. Patients with severe comorbidities or known autoimmune disease were excluded. To date 20 of 26 patients are enrolled. Treatment is in 3 sequential cohorts: (1): NY- ESO-1 OLP-4 vaccine alone (N=3); (2): vaccine and IFA (N=9); (3): vaccine and IFA and Poly-ICLC (N=9). Patients in all 3 cohorts are vaccinated every 3 weeks, for 5 total vaccinations. NY-ESO-1 primary tumor expression is determined by immunohistochemistry, but is not an eligibility criterion. Toxicity is NCI-CTC v3. Immunogenicity: NY-ESO-1 specific humoral immunity (ELISA) and T-cell immunity (tetramer, ELISPOT, and intracellular cytokine staining); and delayed type hypersensitivity (DTH), is assessed on weeks 0,1,4,7,10,13,16. Patients are monitored for progression of disease. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ludwig Institute for Cancer Research
Toll-like receptor agonist therapy can profoundly augment the antitumor activity of adoptively transferred CD8+ T cells without host preconditioning
Authors: Michelle H. Nelson, Jacob S. Bowers, Stefanie R. Bailey, Marshall A. Diven, Caroline W. Fugle, Andrew D. M. Kaiser, Claudia Wrzesinski, Bei Liu, Nicholas P. Restifo, Chrystal M. Paulos
Journal: Journal for ImmunoTherapy of Cancer (2016)

<h3>Background</h3> Lymphodepletion enhances adoptive T cell transfer (ACT) therapy by activating the innate immune system via microbes released from the radiation-injured gut. Microbial components, such as LPS, are key mediators of total body irradiation (TBI) enhancement, but our ability to strategically use these&nbsp;toll-like receptor (TLR) agonists to bolster the potency of T cell-based therapies for cancer remains elusive. Herein, we used TLR4 agonist LPS as a tool to address how and when to use TLR agonists to effectively improve cancer immunotherapy. <h3>Methods</h3> To determine the mechanisms of how innate immune activation via lymphodepletion potentiated antitumor T cell immunity, we utilized the pmel-1 melanoma mouse model. B16F10-bearing mice were preconditioned with 5Gy TBI and given a tripartite ACT therapy (consisting of transferred pmel-1 CD8<sup>+</sup> T cells, vaccination with fowlpox encoding gp100, and IL-2) along with TLR4 agonist LPS. The timing of LPS administration and the requirement of individual components of the tripartite therapy were evaluated based on tumor growth and the phenotype of recovered splenocytes by flow cytometry. We also evaluated the role of non-toxic and clinically used TLR4 and TLR9 agonists—monophosphoryl lipid A (MPL) and CpG Oligodeoxynucleotide (CpG ODN), respectively— for ACT therapy. <h3>Results</h3> Here we report that while exogenous administration of LPS was able to enhance adoptively transferred CD8<sup>+</sup> T cells' tumor destruction, LPS treatment alone did not replace individual components of the tripartite ACT regimen, or obviate TBI. Moreover, we found that sequentially administering LPS during or one day prior to ACT therapy compromised tumor regression. In contrast, administering LPS after ACT potentiated the antitumor effectiveness of the regimen, thereby supporting the expansion of transferred tumor-specific CD8<sup>+</sup> T cells over host CD4<sup>+</sup> T cells. We also found that non-toxic TLR agonists MPL and CpG potentiated the antitumor activity of infused CD8<sup>+</sup> T cells. Finally, TBI was no longer needed to regress tumors in mice who were depleted of host CD4<sup>+</sup> T cells, given a tripartite ACT regimen and then treated with low dose LPS. <h3>Conclusions</h3> Collectively, our results identify how and when to administer TLR agonists to augment T cell-based immunotherapy in the absence or presence of host preconditioning for treatment of advanced malignancies. Our findings have clinical implications for the design of next generation immune-based therapies for patients with cancer.
POCHER (preoperative chemotherapy for hepatic resection) with cetuximab (Cmab) plus CPT-11/5-fluorouracil (5-FU)/leucovorin(FA)/oxaliplatin (L-OHP) (CPT-11-FFL) in unresectable colorectal liver metastases (CLM)
Authors: C. Garufi, A. Torsello, S. Tumolo, M. Mottolese, C. Campanella, M. Zeuli, G. Lo Re, I. Sperduti, G. Pizzi, G. M. Ettorre
Journal: Journal of Clinical Oncology (2009)

e15020 Background: We have previously shown preliminary data with Cmab+ all active drugs, CPT-FFL, with primary end- point CLM resectability (Garufi C. et al ASCO GI 2008). Here we report definitive clinical results. Methods: Unresectability criteria: size&gt;5 cm (a), multinodular (b), ilar location (c), extrahepatic disease (d), &gt;3 stable mets after chemotherapy before surgery (e). Aim of the study was to have at least 30% liver resection rate (power of 80% for p0=10% and p1=25%). Pts received weekly Cmab 400 then 250 mg/m 2 /wk plus CPT-11, 130 mg/m 2 /d1, 6 h infusion, (peak at 13:00) and a 12-h, days 2–5, infusion of L-OHP 20 mg/m 2 /day (peak at 16:00), FA 150 mg/m 2 /day plus 5-FU 600 mg/m 2 /d (peak at 4:00), q 2 wks; after the first 17 pts 5-FU and L-OHP were reduced to 550 and 15 mg/m 2 respectively. Results: Since 07/20/2006 we enrolled 43 pts, irrespective of EGFR, K-ras and gene copy number (gcn): M/F 27/16, median age 60,7 y (33–76), median PS 0. Primary tumor: colon/rectum 34/9, primary tumor resected 39 pts (79%), synchronous metastases: 35 pts (81%), liver &lt;25%/25%: 9/34 ((21/79%); median CEA/CA19–9: 55 ng/ml (1–6,600)/91.8 U/L (2.66440); unresectability: (a): 9 (21%), (b):14 (33%), (c) 1, (d): 4 (9%), (e): 15 (35%). We had 34 partial responses (79%, CI 79.1–87.0), 5 SD (11.6%) and 4 patients not evaluable becouse of toxicity. Complete Resection of CLM was obtained in 27 pts (63%) with 4 pts still to be resected. Median number (n.) of courses (c) was 10 (2–18), median n. of c before surgery (s) was 5 (3–10) and after s was 6 (1–6); median time from last c to s was 2 wks (2–4), from s to recovery chemo was 10 wks (2–16). Median follow-up was12 months, median PFS 13 months (7–19), median OS not reached with 2-y survival of 61%, 8 pts alive without recurrence (19%), 11 deaths (25%).Major limiting toxicity was diarrhea, with no difference after dose reduction: Grade 0–1: 6% of pts, G2 6%, G3 76%, G4 12%; neutropenia G3 6% with no febrile neutropenia. Conclusions: This is the first phase II study with CPT-FFL + Cmab in pts with unresectable CLM. Complete resection was obtained in 63% of pts with diarrhea being limiting toxicity. Analysis of EGFR status, K-ras and gcn will be further presented. No significant financial relationships to disclose.
Comparison of Doripenem and Meropenem as the First-Line Mono-Therapy in Febrile Neutropenic Patients with Acute Leukemia
Authors: Tatsuo Oyake, Yuka Fujisawa, Norifumi Sugawara, Yasuaki Nakagawa, Ichiro Hanamura, Takahiro Mine, Yusei Aoki, Shugo Kowata, Shigeki Ito, Yoji Ishida
Journal: Annals of Oncology (2014)
New insights into <i>HER2</i> expression in breast cancer patients analyzed by qRT-PCR.
Authors: Rong Yu, Kung Y. Chiu, Sunny Lu, Zi-jia Lee, Peter Zhang, Wen Chuan Hsieh, Han-chieh Wu, Ih-jen Su
Journal: Journal of Clinical Oncology (2012)

e11068 Background: HER2 gene status is a key determinant for anti-HER2 therapy with Herceptin. The common methods used for HER2 test in breast cancer patients are IHC and FISH, which are time-consuming and often generate variable results. Quantitative real-time PCR (qRT-PCR) has emerged as a new gold standard technique for quantifying gene expression in different cells and tissues. In this study, we explored the potential of utilizing this technique to determine HER2 expression status in breast cancer patients. Methods: We collected both freshly-frozen and formalin-fixed paraffin-embedded (FFPE) breast tumor samples at three locations. The total RNA was isolated with a RNA extraction kit and was quantified by RiboGreen method. Each sample was normalized against its total RNA concentration and analyzed by a real-time PCR method with inclusion of the Standards and RNA Control. The HER2 expression level was determined by the copy number, C t value, as well as the ΔC t against RNA control. The significance of HER2 expression and correlation among the different groups were analyzed by statistical methods. Results: A total of 80 samples have been tested. We noticed that the RT-PCR method generated very consistent results with little intra- and inter-assay variance. We also noticed that HER2 expression in the fresh tumor samples exhibited two distinct populations, although HER2 expression in the normal fresh samples showed the continuous distribution. Similar results were obtained with the FFPE samples. Study of the other breast cancer-related genes, such as EGFR, ER-a, BRCA1, and BRCA2, revealed that their expression, unlike HER2, followed a pattern of continuous distribution. In comparison with FISH test, qRT-PCR method not only produced consistent results, but also able to differentiate breast tumors into two distinct groups, HER2 positive vs. HER2 negative. Conclusions: The qRT-PCR is a more reliable method than the currently used IHC and FISH for HER2 test. Showing two distinct groups of HER2 expression by qRT-PCR further warrants its application in testing HER2 gene status for breast cancer patients.
Prognostic factors in disseminated germ cell tumors.
Authors: C J Logothetis, M L Samuels
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.8.1278 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3016207 Prognostic factors in disseminated germ cell tumors. C J LogothetisxC J LogothetisSearch for articles by this author , M L SamuelsxM L SamuelsSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.8.1278 First Page PDF © 1986 by American Society of Clinical Oncology
In patients with hypertension, β-blockers in the 120 d before noncardiac surgery were linked to CV events and death
Authors: Louise Moist
Journal: Annals of Internal Medicine (2016)

Source Citation Jørgensen ME, Hlatky MA, Køber L, et al. β-blocker-associated risks in patients with uncomplicated hypertension undergoing noncardiac surgery. JAMA Intern Med. 2015;175:1923-31. 26436291
Phase I/II study of PHY906/capecitabine in hepatocellular carcinoma
Authors: M. G. Rose, Y. Yen, S. So, M. W. Saif, E. Chu, S. Liu, Z. Jiang, A. Foo, R. Tilton, Y. Cheng
Journal: Journal of Clinical Oncology (2007)

15152 Traditional botanical formulations in combination with conventional antitumor chemotherapeutics may prove a powerful approach in reducing toxicity and improving clinical outcomes. In vivo studies show that PHY906, a traditional Chinese formulation, can reduce chemo-induced gastrointestinal toxicity while enhancing the therapeutic efficacy of a broad-spectrum of common anticancer agents in various cancer models, including capecitabine, CPT-11, thalidomide, adriamycin, and sorafenib in liver cancer; gemcitabine, capecitabine, oxaliplatin, gem/ox in pancreatic cancer; and CPT-11, 5-FU, sorafenib, VP-16, L-OddC, CPT-11/5-FU/LV, and oxaliplatin/5-FU/LV in colorectal cancer. Co- administration of PHY906 with a host of chemotherapeutic agents appears to neither alter the pharmacokinetic profiles of the chemotherapeutic agents nor their respective metabolites. PHY906 is currently being studied in a phase I/II, multicenter, open-label, dose-modification, safety and efficacy study in combination with capecitabine in patients with non-resectable HCC in the U.S. and Taiwan. Phase I patients (n=18) were enrolled at COH, Yale, VA and Stanford beginning November 2003. The primary objective of phase I was the determination of a safe dose regimen by varying the dose levels of PHY906 and/or capecitabine. Three dose levels of PHY906 + capecitabine were evaluated: PHY906 1000 mg BID + Capecitabine 1000 mg/m 2 BID; PHY906 600 mg BID + Capecitabine 750 mg/m 2 BID; and PHY906 800 mg BID + Capecitabine 750 mg/m 2 BID. The final dosing level was chosen for the phase II portion of the study. Preliminary results suggest that the quality of life of patients on PHY906 + capecitabine was improved when compared to historical controls studying capecitabine alone. There is also no evidence of drug-induced toxicity caused by PHY906; nor does PHY906 reduce capecitabine antitumor activity. For patients receiving capecitabine at 750 mg/m 2 BID and PHY906 at either 600 mg BID (N=4) or 800 mg BID (N=24), 10.7% (N=3) achieved minor response (MR), 50% (N=14) had stable disease (SD) and 39.3% (N=11) had progressive disease (PD). These findings support the further investigation of PHY906 as an adjuvant therapy of capecitabine in a larger HCC population. No significant financial relationships to disclose.
Second-line chemotherapy in advanced gastric cancer: A retrospective, single-center analysis
Authors: C. Herrmann, D. Jaeger, T. Herrmann
Journal: Journal of Clinical Oncology (2007)

15170 Background: The role of second-line chemotherapy in advanced gastric cancer is not yet established. We analyzed patients with advanced gastric cancer treated at our department between 2002 and 2005 comparing the outcome of patients with first-line chemotherapy only and those who received second-line chemotherapy. Patients and Methods: 51 patients with metastatic or recurrent histologically confirmed gastric cancer were analyzed in this retrospective study. The choice of chemotherapy depended on the attending physician. Results: Altogether, 17 patients (33.3 %) were treated with only one chemotherapy regimen, whereas 34 patients (66.6 %) received at least two different chemotherapy regimens. During the last years, the preference for certain chemotherapy regimens changed. At the time of analysis, 9 patients were still alive. Median overall survival was 11 months (range: 1–41). Patients who received only one chemotherapy regimen were older (median age 70, range: 47–81), had a shorter TTP (3.5 months, range: 1–15) and a shorter overall survival (6 months, range: 2–25) than patients receiving sequential chemotherapies (median age 61.5 (range: 33–79) p = 0,009, TTP under first-line therapy 5 months (1–17), p = 0,45, overall survival 14.5 months (2–41), p = 0,001). Response to second-line chemotherapy was assessed in 32 patients: Partial remission was detected in 4 patients (12.5 %), stable disease for = 3 months in 15 patients (46.8 %), whereas disease progression occurred in 12 patients (37.5 %). 10 of 51 patients (19.6 %) received more than two different treatments: 4 patients had third-line chemotherapy, 6 patients had more than 3 different therapies. Overall survival was 13 months (11–22) for patients with third-line chemotherapy and 29 months (16–41) for patients receiving more than three different treatment regimens. Conclusion: Although a number of active antineoplastic drugs are available for the treatment of advanced gastric cancer, the prognosis is still poor. Selected patients may benefit from salvage chemotherapy after failure of first-line chemotherapy. No significant financial relationships to disclose.
Rumpel-Leede Phenomenon Associated With Tourniquet-like Forces of Baby Carriers in Otherwise Healthy Infants
Authors: Tuyet A. Nguyen, Daniel Garcia, Audrey S. Wang, Sheila Fallon Friedlander, Andrew C. Krakowski
Journal: JAMA Dermatology (2016)

local hypothermia, topical 99% dimethyl sulfoxide, oral corticosteroids, celecoxib, and pyridoxine. 1 Though the eruption is self-limited, it can delay chemotherapy and if severe, may require dose reduction or changing chemotherapeutic regimens.Over half of patients have a recurrent eruption with restitution of the offending agent, and there is no way to prevent TEC. 5 It has been proposed that treatments for hyperhidrosis such as topical aluminum chloride, iontophoresis, or botulinum toxin injection, could be used for prevention of TEC. 6 The absence of cutaneous reaction in an area of hypohidrosis in this patient suggests that these interventions may be effective as TEC prophylaxis.If successful, the ability to prevent TEC by decreasing sweat production would have a significant benefit for patients who would otherwise have to reduce chemotherapy dose or switch regimens.
Randomized phase II study of sequential versus concurrent chemoradiotherapy (CRT) in poor- risk patients with inoperable stage III non-small cell lung cancer (NSCLC): Interim analysis
Authors: F. Cardenal, M. D. Arnaiz, D. Isla, J. Valencia, N. Viñolas, M. Dómine, F. J. Pérez, I. Maestu, C. Mesia, R. García
Journal: Journal of Clinical Oncology (2005)

7255 Background: There is no standard treatment for poor-risk patient with inoperable stage III NSCLC. The purpose of this study was to explore if combined chemotherapy and radiotherapy is feasible, tolerable and effective in patients > 75 years old and/or PS 2, and/or weight loss >5% and/or comorbidity. A first step analysis was planned and has been carried out (Simon method). Methods: Patients with inoperable stage IIIA and B NSCLC and at least one of the following: age > 75 years, ECOG 2, weight loss > 5%, creatinine clearance < 60 ml/min, a comorbid condition precluding the patient to be treated in a protocol for fit patients,were randomized to receive either carboplatin AUC 2.5 and vinorelbine 15 mg/m2 both on days 1,8,15 and 29 and thoracic radiotherapy (TRT) total dose 60 Gy starting day 1 (Arm A, concurrent) or carboplatin AUC 5, days 1 and 29 and vinorelbine 25mg/m2 days 1, 8, 22 an 29 followed by TRT 60 Gy (Arm B, sequential) Results: From June 2001 to September 2004, 46 pts have been randomized, 44 have received tratment: 23 in arm A and 21 in arm B. Median age 74(49–84), male 96%, stage IIIA 26%, stage IIIB 74%,ECOG 2, 33%, weight loss >5% 37%, comorbidity 54%. More than one poor-risk inclusion criteria: 57%. Treatment groups were well balanced. Thirty-six pts completed treatment (82%), 91% in arm A and 71% in arm B. There were 1CR and 20 PR (RR 46%), 11SD(25%),7 PD (16%) Fifteen (1 CR, 14 PR) responses in arm A and 6 PR in arm B. Grade 3–4 hematological toxicity was less than 5%.Grade 3 esophagitis:3%, Grade 3–4 dyspnea: 14%. Four deaths during treatment: 1 in arm A and 3 in arm B (none primarily related to treatment). Median survival and 1-year survival rate were 7,5 months (CI:4.7–10.3m) and 40% (CI 25–56%) respectively. Conclusion: Concurrent CRT is feasible and well tolerated. A decision has been made to continue the study with the concurrent CRT arm as a single arm. No significant financial relationships to disclose.
Abstract 12921: Left Atrial Dysfunction and Cryptogenic Stroke: Novel Insights from Transthoracic Echocardiography
Authors: Darryl P Leong, Emer Joyce, Philippe Debonnaire, Spyridon Katsanos, Martin J Schalij, Eduard R Holman, Jeroen J Bax, Victoria Delgado, Nina Ajmone Marsan
Journal: Circulation (2012)

Darryl P Leong, 2012 Finalist and Presenting Author
The cytochrome b and ATPase genes of honeybee mitochondrial DNA.
Authors: R H Crozier, Y C Crozier
Journal: Molecular Biology and Evolution (1992)

The gene sequences for honeybee cytochrome b, ATPase 6, and ATPase 8 are presented, along with the inferred amino acid sequences of the proteins. These mitochondrial genes are in the same relative positions as are their counterparts in Drosophila mitochondrial mtDNA and have evolved at a significantly greater overall rate than have those of Drosophila. Comparisons using both amino acid identity and the proportion of conservative replacements between the inferred Apis and vertebrate cytochrome b sequences shows the two highly conserved sections reported by Howell, but his recognition of five conserved regions is not well supported. A very high AT bias is reflected in very high codon biases. The best predictors of the number of occurrences of an amino acid in honeybee cytochrome b are the T and G contents of its codon family--unlike the case for vertebrate cytochrome b, in which the codon family size and AT bias are the strongest predictors; protein function, at least as judged by hydrophilicity characteristics, appears to be unaffected by these differing influences on amino acid composition.
Promises and Challenges of Smac Mimetics as Cancer Therapeutics
Authors: Simone Fulda
Journal: Clinical Cancer Research (2015)

Abstract Inhibitor of Apoptosis (IAP) proteins block programmed cell death and are expressed at high levels in various human cancers, thus making them attractive targets for cancer drug development. Second mitochondrial activator of caspases (Smac) mimetics are small-molecule inhibitors that mimic Smac, an endogenous antagonist of IAP proteins. Preclinical studies have shown that Smac mimetics can directly trigger cancer cell death or, even more importantly, sensitize tumor cells for various cytotoxic therapies, including conventional chemotherapy, radiotherapy, or novel agents. Currently, several Smac mimetics are under evaluation in early clinical trials as monotherapy or in rational combinations (i.e., GDC-0917/CUDC-427, LCL161, AT-406/Debio1143, HGS1029, and TL32711/birinapant). This review discusses the promise as well as some challenges at the translational interface of exploiting Smac mimetics as cancer therapeutics. Clin Cancer Res; 21(22); 5030–6. ©2015 AACR. See all articles in this CCR Focus section, “Cell Death and Cancer Therapy.”
Prognostic Significance of Ploidy Level in Human Tumors. I. Carcinoma of the Uterus2
Authors: N. B. Atkin
Journal: JNCI Journal of the National Cancer Institute (1976)

The 5-year survival rates of 540 patients with carcinoma of the cervix and 186 with carcinoma of the corpus uteri were assessed in relation to the modal DNA values of the tumors. Patients with squamous cell cervical carcinomas had more favorable prognoses if the modes were near-triploid or hypotetraploid; however, these high-ploidy tumors included more stage III cases than did the tumors with near-diploid modes. Patients with near-diploid endometrial carcinomas has considerably more favorable prognosis than did patients with the minority of tumors at this site, who had high modes; this prognostic difference was only partly related to a higher proportion of poorly differentiated tumors in the high-ploidy group since, among the poorly differentiated tumors, individuals with near-diploid modes again had significantly better prognoses than those with high modes.