tbuckley/cabot-search huggingface dataset:
A phase I study of antisense Bcl-2 oligonucleotide (G3139) in combination with carboplatin (C) and paclitaxel (T) in patients with advanced solid tumors
Authors: M. Lalich, G. Wilding, J. Kolesar, D. G. McNeel, K. Schell, C. Leith, R. Chappell, R. Marnocha, D. Alberti, G. Liu
Journal: Journal of Clinical Oncology (2006)

13006 Background: G3139 is an 18-mer oligonucleotide that targets the mRNA of Bcl-2, a protein that inhibits apoptosis conferring treatment resistance, and is synergistic with taxanes in studies using Bcl-2 over-expressing xenografts. Here we conduct a study combining G3139 with C + T in order to define the recommended phase II dose, as well as evaluate the direct biologic effect of G3139 on tumor. Methods: Patients with advanced solid tumors were treated with a dose escalation of G3139 (3–7 mg/kg/day) by continuous infusion days 1–7, with C (AUC 5) and T (150 mg/m 2 ) given on day 4, repeated in 3 week cycles. At the planned expanded cohort (G3139 7 mg/kg/day dose), 12 patients underwent paired tumor biopsies (baseline and day 4 pre-chemotherapy) for assessment of Bcl-2/Bax expression by RT-PCR and IHC, as well as intratumoral G3139 levels using ELISA. Likewise, peripheral blood mononuclear cells (PBLs) were assessed using flow cytometry and RT-PCR for changes in Bcl-2/Bax expression. Results: 34 patients have been treated: 11 melanoma, 7 bladder, 3 prostate, 2 esophageal, 3 non-small cell lung, and 1 head/neck, kidney, breast, pancreas, liver, gastrointestinal stromal, biliary, and unknown primary cancers. G3139/C/T appeared well tolerated at the doses administered with the main toxicities observed being attributed to the C + T chemotherapy (myelosuppression and thrombocytopenia). The maximal tolerated dose is yet to be achieved. Assessment of paired tumor biopsies on 12 patients show decreases in Bcl-2 transcription in laser capture microdissected tumor using RT-PCR, with concordance observed using IHC. Likewise, decrease in Bcl-2 gene expression in PBLs was seen. 2 confirmed PRs were observed, including a bladder patient with baseline Bcl-2 tumor expression 10-fold greater than any other patient assessed. Conclusions: G3139/C/T is well tolerated, with main toxicities attributable to the chemotherapy alone. Bcl-2 is suppressed in tumor and PBLs supporting that a biologically active dose of G3139 is being achieved. Currently, the C + T is being escalated to define a MTD. Complete clinical data, G3139 pharmacokinetics, and Bcl-2/Bax data will be presented in detail. No significant financial relationships to disclose.
Dose reduction of etoposide in jaundiced patients.
Authors: M J Ratain
Journal: Journal of Clinical Oncology (1990)

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.1990.8.12.2088 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2230900 Dose reduction of etoposide in jaundiced patients. M J RatainxM J RatainSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.12.2088 PDF "Dose reduction of etoposide in jaundiced patients.." Journal of Clinical Oncology, 8(12), pp. 2088–2089© 1990 by American Society of Clinical Oncology
Final analysis of a multi-center, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo (P) in patients (pts) with malignant mesothelioma (MM)
Authors: T. Karrison, H. L. Kindler, D. R. Gandara, C. Lu, T. L. Guterz, K. Nichols, H. Chen, W. M. Stadler, E. E. Vokes
Journal: Journal of Clinical Oncology (2007)

7526 Background: In phase II trials in MM, GC on a 21-day (D) schedule has response rates of 16%–26% and median overall survival (OS) of 9.6–13 months (mo). Since VEGF has a key role in MM biology, we added anti-VEGF antibody B to GC in a multi-center, double- blind, placebo-controlled randomized phase II trial. Methods: Eligible pts had unresectable MM; no prior chemotherapy; PS 0–1; no thrombosis, bleeding, or major vessel invasion. Primary endpoint: progression-free survival (PFS). Statistics: 90% power to detect HR 0.57. Stratification: PS (0/1), histology (epithelial/other). G 1,250 mg/m 2 D 1, 8 Q21D, C 75 mg/m 2 D1 Q21D, and B 15 mg/kg or P D1 Q21D was given × 6 cycles, then B or P Q21D until progression. Baseline plasma VEGF was measured. 115 pts enrolled 12/01- 07/05 at 11 sites, 108 (GCB/GCP) 53/55 were evaluable. Male 74%/84%; median age 62/65 (range 44–78/20–84); PS 1 55%/47%; epithelial 74%/67%; pleural 93%/91%; thrombocytosis 40%/40%. Results: Cycles: total 458/424, median 7/6, range 1–42/2–39. Statistically significantly different (SSD) toxicity (p &lt;0.05), any grade: alopecia 60%/38%; epistaxis 62%/24%; hypertension 45%/22%; non-neutropenic infection 15%/4%; proteinuria 62%/47%; stomatitis 23%/7%. There were no SSD toxicities = grade 3. Median PFS 6.9/6.0 mo (HR 0.93, p=0.88). Median OS 15.6/14.7 mo (p=0.91). 1-year survival 59%/57%. Partial response 25%/22%; stable disease 51%/60%. Median VEGF (N=56) 131/154 pg/ml (range 31–1760/5–1786). Higher VEGF was associated with shorter PFS (p=0.02) and OS (p=0.0066). In pts with VEGF = the median, PFS (p=0.043) and OS (p=0.028) were significantly greater for GCB than GCP; in high VEGF strata this was not SSD. Conclusion: Adding B to GC in MM pts does not yield statistically significant differences in PFS, OS, response, or grade ¾ toxicity. GCB-treated pts with low VEGF levels had longer PFS and OS. Supported by NCI grant N01-CM-17102. No significant financial relationships to disclose.
Occurrence, severity and longitudinal course of symptoms in 1129 patients during radiation therapy
Authors: K. M. Mustian, J. T. Hickok, G. R. Morrow, J. A. Roscoe, P. Okunieff
Journal: Journal of Clinical Oncology (2005)

8039 Background: Little information is available from large patient samples concerning when symptoms first appear, how they compare to each other in frequency and severity, and how symptoms worsen or improve during radiation treatment (RT). Methods: Patients were asked to complete a Symptom Inventory (SI) on Monday of each week they received RT. Patients indicated the severity of 12 symptoms (fatigue, pain, nausea, disturbed sleep, feeling upset, shortness of breath, memory difficulty, lack of appetite, drowsiness (sleepiness), vomiting, skin problems and difficulty urinating) “in the past week” on an 11-point scale anchored by 0 = “Not Present” and 10 = “As Bad As You Can Imagine.” Results: 1129 patients completed a baseline SI within one week of beginning RT, and 419 of these also completed a SI each week for the following four weeks of RT (five data points). 84% of the 1129 patients experienced at least one symptom at baseline (mean 4 per patient) and nearly 11% had 9 or more symptoms. Fatigue (68%), drowsiness (60%) and sleep problems (51%) were the most frequent, as well as, the most intense symptoms, with ratings of 7 or higher by 13%, 9% and 10% of patients, respectively. Vomiting (10%), urinary symptoms (18%) and skin problems (17%) were the least common and also the least severe (rated as 7 or higher by < 2%). Significantly more symptoms were noted by females than males and by younger than older patients. In the sub-sample of patients with data at all five time points, the prevalence and severity of all symptoms, with the exception of memory loss, increased over time. Fatigue was the most severe symptom at all five assessments. Skin problems posted the largest increase; from 11% of patients at baseline to 72% by week 5. Conclusions: While most patients had symptoms at baseline, the worsening of nearly all symptoms over time suggests that RT is a significant additional cause of patients’ discomfort. Supported, in part, by ACS grant RSG-01–071-PBP No significant financial relationships to disclose.
Inhibition of DNA and RNA Synthesis, but Minimally of Protein Synthesis, in Human Leukemia Cells by a Serine Antimetabolite 2
Authors: Nelson Pazmiño, D. G. Doherty, James D. Regan
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Inhibition of DNA and RNA Synthesis, but Minimally of Protein Synthesis, in Human Leukemia Cells by a Serine Antimetabolite Get access Nelson Pazmiño, Nelson Pazmiño Search for other works by this author on: Oxford Academic PubMed Google Scholar D. G. Doherty, D. G. Doherty Search for other works by this author on: Oxford Academic PubMed Google Scholar James D. Regan James D. Regan Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 3, September 1973, Pages 761–765, https://doi.org/10.1093/jnci/51.3.761 Published: 01 September 1973 Article history Received: 05 March 1973 Accepted: 18 May 1973 Published: 01 September 1973
Thymidylate Synthase Levels: Prognostic, Predictive, or Both?
Authors: Carmen Allegra
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.7.1711 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11919223 Thymidylate Synthase Levels: Prognostic, Predictive, or Both? Carmen AllegraxCarmen AllegraSearch for articles by this author Show More National Cancer Institute, Bethesda, MD https://doi.org/10.1200/JCO.2002.20.7.1711 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Concomitant delineation of <i>HER2</i> gene amplification and protein expression status using a two-color bright field immunogenotypic assay (SISHPro <i>HER2</i>)
Authors: R. R. Tubbs, H. Nitta, F. Gaire, M. Dietel, M. Loftus, J. Pettay, T. M. Grogan
Journal: Journal of Clinical Oncology (2008)

22006 Background: Although gene amplification is the mechanism of HER2 over-expression in most breast carcinomas, discordance does occur between results of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Testing algorithms reflex screening IHC 2+/equivocal cases to FISH resulting in delays in reporting of HER2 status. Furthermore, 0 or 1+ IHC staining in overtly HER2 gene amplified cases is well-documented, as are cases that are not amplified for HER2 but over-express the encoded protein. We assessed the analytical performance of a combined immunogenotypic bright field assay for determination of HER2 status. Methods: 53 invasive ductal carcinomas of the breast for which HER FISH results as assessed by the HER2/CEP17 PathVysion assay (Abbott Molecular), and HER2/CHR17 status as assessed by Silver In Situ Hybridization (SISH) (Ventana), were evaluated using a novel immunogenotypic assay. This approach utilized HER2 antibody clone 4B5 IHC with alkaline phosphatase fast red K for detection of protein over-expression (red) and SISH (metallic silver; black) to simultaneously evaluate the expression and copy number of the HER2 gene. SISHPro slides were scored independently without knowledge of historical FISH, SISH, or IHC results using conventional bright field microscopy. Results: Overall concordance of the SISH component of SISHPro with FISH was excellent (94%). Three cases (6%) of gene/protein discordance attributable to immunogenotypic heterogeneity were readily identified on a cell by cell basis using SISHPro. Conclusions: Concomitant immunogenotyping for HER2 status was readily accomplished using a bright field assay that simultaneously assessed gene copy number by SISH and HER2 protein expression by IHC using peroxidase and alkaline phosphatase systems respectively. This approach allows more efficient utilization of limited needle biopsy material and provides immediate internal reinforcement between immunotype and genotype for HER2 testing. Gene/protein discordances, and genotypic and phenotypic heterogeneity, are readily identified for use in future outcome studies that will determine the clinical significance of discordant gene and protein status in breast carcinoma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ventana Medical Systems International, Ventana Medical Systems, Inc. Ventana Medical Systems International, Ventana Medical Systems, Inc. Ventana Medical Systems, Inc. Ventana Medical Systems International, Ventana Medical Systems, Inc.
Foreign-Body Tumorigenesis: No Requirement for Tissue Anoxia2
Authors: Richard D. Karp, Kenneth H. Johnson, Lance C. Buoen, Inge Brand, K. Gerhard Brand
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Foreign-Body Tumorigenesis: No Requirement for Tissue Anoxia Get access Richard D. Karp, Richard D. Karp Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota 55455; and Department of Veterinary Pathology and Parasitology, College of Veterinary Medicine, St. Paul, Minnesota 55101 Search for other works by this author on: Oxford Academic PubMed Google Scholar Kenneth H. Johnson, Kenneth H. Johnson Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota 55455; and Department of Veterinary Pathology and Parasitology, College of Veterinary Medicine, St. Paul, Minnesota 55101 Search for other works by this author on: Oxford Academic PubMed Google Scholar Lance C. Buoen, Lance C. Buoen Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota 55455; and Department of Veterinary Pathology and Parasitology, College of Veterinary Medicine, St. Paul, Minnesota 55101 Search for other works by this author on: Oxford Academic PubMed Google Scholar Inge Brand, Inge Brand Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota 55455; and Department of Veterinary Pathology and Parasitology, College of Veterinary Medicine, St. Paul, Minnesota 55101 Search for other works by this author on: Oxford Academic PubMed Google Scholar K. Gerhard Brand K. Gerhard Brand 5 Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota 55455; and Department of Veterinary Pathology and Parasitology, College of Veterinary Medicine, St. Paul, Minnesota 55101 5Address reprint requests to: K. G. Brand, University of Minnesota Medical School, Mayo Box 196, Minneapolis, Minn. 55455. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 5, May 1973, Pages 1403–1405, https://doi.org/10.1093/jnci/50.5.1403 Published: 01 May 1973 Article history Received: 13 March 1973 Accepted: 14 March 1973 Published: 01 May 1973
Identification of a Gene Locus for Senior-Løken Syndrome in the Region of the Nephronophthisis Type 3 Gene
Authors: Heymut Omran, GU[Combining Diaeresis]rsel Sasmaz, Karsten Ha[Combining Diaeresis]ffner, Andreas Volz, Heike Olbrich, Rachid Melkaoui, Edgar Otto, Thomas F. Wienker, Rudolf Korinthenberg, Matthias Brandis, Corinne Antignac, Friedhelm Hildebrandt
Journal: Journal of the American Society of Nephrology (2002)

Senior-Løken syndrome is an autosomal recessive disease with the main features of nephronophthisis (NPH) and Leber congenital amaurosis. The gene for adolescent nephronophthisis (NPHP3) was recently localized to chromosome 3q21-q22. The hypothesis was tested that Senior-Løken syndrome (SLS) might localize to the same region by studying a kindred of German ancestry with extended consanguinity and typical findings of SLS. Twenty highly polymorphic markers located in the vicinity of the NPHP3 genetic region were tested. Haplotype analysis revealed homozygosity by descent in affected individuals, and linkage analysis yielded a parametric maximum multipoint logarithm of likelihood of odds (LOD) score of 3.14, thus identifying the first locus for SLS. The SLS1 locus is flanked by D3S1587 and D3S621 and contains a 14-cM interval that contains the whole critical NPHP3 region. Three additional families with SLS were studied, and evidence for genetic heterogeneity in one of them was found. Localization of a SLS locus to the region of NPHP3 opens the possibilities of both diseases arising by mutations within the same pleiotropic gene or two adjacent genes.
Prognostic value of immunohistochemical phenotypes (IP) of 141 operable breast cancer patients (pts) included in phase III trials of adjuvant therapy
Authors: R. Trujillo, E. Gallego, A. Márquez, N. Ribelles, J. Trigo, D. Perez, C. Quero, A. Medina, L. Vicioso, E. Alba
Journal: Journal of Clinical Oncology (2007)

21040 Background: Gene expression arrays and IP studies classified breast cancer in three distinct subtypes: basal, HER2/neu and luminal that are associated with different clinical outcomes. Methods: In 141 pts with operable breast cancer, included in phase III trials of adjuvant therapy in our center, immunohistochemical staining was performed on 3μm sections of paraffin blocks, containing tissue-arrays of tumour tissue.A basal phenotype (BP) was defined by negative estrogen receptor (ER) and progesterone receptor (PR) and positive cytokeratin (CK) 5/6 or EGFR immunoreactivity. HER2/neu phenotype as positive c-erb B2 by HercepTest™ and luminal phenotype (LP) by positive ER, PR and CK 7/8 and negative HER-2. Survival curves were calculated by the Kaplan-Meier method. The differences between survivals were estimated using the log rank test. Multivariate Cox regression analysis was used to evaluate any independent prognostic effect of the variables on disease-free survival (DFS). Results: Complete clinical follow-up information was available for 141 pts. The median follow-up period was 52 months (range 1–103 months). During this period, 13.8% pts died from breast cancer and 27.7% pts relapsed. At the time of the primary diagnosis 10.4% of the pts had lymph node negative disease and 89.6% had positive lymph nodes. 50.8% pts received taxane chemotherapy, 7.7% Trastuzumab, 62.3% radiotherapy and 61% pts received hormonotherapy. Positivity for LP was 65.2%, BP 9.9% and Her-2 phenotype 8.5%. 16.3% didn't fit for any of the three subtypes. Median DFS for BP: 24 moths, for LP and Her-2 phenotypes median DFS was not reached. 5 years DFS were; BP: 19%, LP: 63% and Her-2: 56%. Kaplan-Meier survival analyses demonstrated that the presence of a detectable BP was highly significantly associated with a worse DFS compared with the presence of a LP, log rank test (p= 0.0001). Multivariate Cox regression analyses estimated that the prognostic effect of BP in relation to DFS was independent of lymph node, stage and tumor size, HR: 0.12 95% CI (0.05–0.2). Conclusions: We found that expression of BP was associated with poor prognostic in the context of randomized phase III trials. No significant financial relationships to disclose.
CA125 and malignant lymphomas.
Authors: C Sebban, Y Lasne, V Berenguer, E Archimbaud, Y Devaux, J J Viala
Journal: Journal of Clinical Oncology (1991)

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.1991.9.2.359 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 1988582 CA125 and malignant lymphomas. C SebbanxC SebbanSearch for articles by this author , Y LasnexY LasneSearch for articles by this author , V BerenguerxV BerenguerSearch for articles by this author , E ArchimbaudxE ArchimbaudSearch for articles by this author , Y DevauxxY DevauxSearch for articles by this author , J J VialaxJ J VialaSearch for articles by this author https://doi.org/10.1200/JCO.1991.9.2.359 PDF "CA125 and malignant lymphomas.." Journal of Clinical Oncology, 9(2), pp. 359–360© 1991 by American Society of Clinical Oncology
N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine in combination with cyclophosphamide: an active, low-toxicity regimen for metastatic hormonally unresponsive prostate cancer.
Authors: L J Brandes, S P Bracken, E W Ramsey
Journal: Journal of Clinical Oncology (1995)

PURPOSE The intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine. HCl (DPPE), potentiates chemotherapy cytotoxicity to malignant cells but protects normal tissue, including bone marrow, gut, and hair. We assessed the response to and clinical toxicity of DPPE/cyclophosphamide therapy in 20 patients with advanced hormonally unresponsive prostate cancer, 19 of whom were symptomatic. PATIENTS AND METHODS Subjects received a maximally tolerated dose of DPPE (6 mg/kg) intravenously (IV) over 80 minutes. Cyclophosphamide (600 to 800 mg/m2; maximum dose, 1,500 mg) was administered over the last 20 minutes of DPPE infusion. Treatments (usually outpatient) were given once weekly for 4 weeks, followed by a 1-week delay, and then 2 of every 3 weeks as long as the patient was deemed to benefit. RESULTS Five of seven patients (71%) with measurable soft tissue disease had a partial remission (PR). Three of 16 (19%) with assessable bone disease responded (one complete remission [CR] and two PRs). Nine of 18 (50%) with an elevated serum level of prostate-specific antigen (PSA) had more than a 50% (mean +/- SD, 78% +/- 14%) decrease. Eleven of 13 (85%) with bone pain had partial or complete resolution of this symptom; the PSA level and bone scan improved in six and two of these subjects, respectively. Acute treatment toxicity consisted of nausea/vomiting (six of 20) and ataxia (20 of 20), which correlated with peak serum levels of DPPE. Delayed effects (24 to 48 hours) consisted mainly of tiredness and mild nausea; one patient developed hemorrhagic cystitis. Bone marrow and hair follicle toxicity was negligible in 14 and 15 patients, respectively. CONCLUSION DPPE/cyclophosphamide appears to be an active regimen for metastatic prostate cancer, with the added benefit of relatively low toxicity.
Predictive utility of RRM1 promoter polymorphisms on outcome of patients with non-small cell lung cancer
Authors: E. B. Haura, Z. Zheng, A. Gautam, S. Sharma, A. Cantor, A. Sharma, G. Bepler
Journal: Journal of Clinical Oncology (2004)

7155 Background: RRM1 is a gene crucial for determination of the tumor phenotype. It encodes the regulatory subunit of ribonucleotide reductase, and it is a molecular target of gemcitabine. In addition, RRM1 induces PTEN expression and inhibits cell migration, invasion, and metastasis formation. In patients with resected lung cancers, increased levels of RRM1 are highly associated with long survival. In contrast, patients on gemcitabine and cisplatin therapy for advanced disease have a poor survival if RRM1 expression is high presumably because of decreased efficacy of chemotherapy. Methods: We analyzed the RRM1 promoter for polymorphisms in an effort to develop a practical and inexpensive assay for RRM1 expression. Results: Two single nucleotide polymorphisms, RR37 and RR524, were discovered. These polymorphisms impacted promoter activity in vitro. Promoter allelotypes were highly associated with overall (p=0.06) and disease-free (p=0.03) patient survival. The allelotype with the highest predicted activity was associated with the best patient outcome. However, we did not find an association between allelotype and tumoral RRM1 expression. This is likely a result of the limited impact of the described promoter polymorphisms on overall in vivo gene expression. Conclusions: We conclude that clinical studies using RR37 and RR524 for decisions on chemotherapy are premature and that further functional studies on the RRM1 promoter are required to fully elucidate factors controlling RRM1 expression. No significant financial relationships to disclose.