tbuckley/cabot-search huggingface dataset:
Outcome of initially unresectable metastatic colorectal cancer (MCRC) patients (pts) treated with first-line FOLFOXIRI followed by R0 surgical resection of metastases (mts)
Authors: G. Masi, F. Loupakis, L. Fornaro, G. Baldi, S. Cupini, S. Di Donato, R. Ferraldeschi, C. Sonaglio, C. Granetto, A. Falcone
Journal: Journal of Clinical Oncology (2008)

4074 Background: Prognosis of pts with initially unresectable MCRC can be improved if chemotherapy induces a significant down- sizing of disease thus allowing an R0 surgical resection of mts. The activity of the regimen used is correlated with the rate of R0 resections and the GONO-FOLFOXIRI improved the rate of R0 resection over FOLFIRI (Falcone, JCO’07). The objective of this analysis is to evaluate whether the increase in the rate of resection is also associated with a favorable outcome in the long term. Methods: Overall 196 pts with initially unresectable MCRC and not selected for a neo-adjuvant strategy were treated with FOLFOXIRI (irinotecan 165 mg/sqm d1, oxaliplatin 85 mg/sqm d1, l-LV 200 mg/sqm d1, 5FU 3200 mg/sqm 48-h continuous infusion starting on d1, repeated every 2 weeks) in phase II and III trials. This regimen was associated with an elevated activity (ORR: 66%-72%) and 37 patients (19%) could undergo to a secondary R0 surgery on mts. Results: Characteristics of the 37 radically resected pts were: median age 64 years (45–73), ECOG PS ≥1: 30%, median CEA: 10 ng/ml (1–288), liver involvement ≥ 25%: 43%. Sites of disease were liver only: 68%, lung only: 11%, liver + lymphnodes: 13%, liver + peritoneum: 3%, liver + lung: 5%. Mts were synchronous in 68% of pts. Pre-operative FOLFOXIRI was administered for a median of 11 cycles (3–15). There was no perioperative mortality. After a median follow up of 61 mos median OS is 41+ mos, 5-year and 8-year survival are 45% and 33% respectively. In 11 pts (36%) progressed after surgery a surgical re-resection and/or radiofrequency ablation was performed. Up today 29% of pts are free of disease. The analysis of treatment-induced liver injury (so far performed on 17 patients) has not shown nor steato-hepatitis, nor G3 steatosis, nor G3 vascular toxicity. Conclusions: The GONO-FOLFOXIRI not only improves the rate of R0 surgery in unresectable MCRC pts, but also survival of resected pts is considerable and compares well to that achieved with other regimens. Furthermore neoadjuvant FOLFOXIRI for 3–6 months is safe and not associated with unexpected adverse events or severe liver injury. Supported by Fondazione ARCO. No significant financial relationships to disclose.
Response to azacitidine in patients with myelodysplastic syndrome with marrow fibrosis
Authors: R. Juvvadi, J. M. Rossetti, R. K. Shadduck, R. B. Kaplan, M. Kennedy, W. Kramer, J. Lister
Journal: Journal of Clinical Oncology (2007)

7089 Background: The Myelodysplastic syndrome (MDS) is characterized by aberrant hematopoietic progenitor cell maturation resulting in ineffective hematopoiesis, cytopenia and progression to acute myeloid leukemia. Some individuals with MDS also have fibrosis within the marrow. MDS with marrow fibrosis appears to be biologically and clinically distinct from myeloproliferative disorders with marrow fibrosis such as agnogenic myeloid metaplasia. While azacitidine (AZA), a DNA methyl transferase inhibitor has known activity in MDS, little is known about its efficacy in patients with MDS with marrow fibrosis. Methods: The records of 41 patients with MDS with marrow fibrosis treated with AZA were reviewed. The degree of fibrosis was determined by reticulin staining and ranged from 1+ to 3+. Patients who received at least 2 cycles were considered evaluable for response. All patients were evaluated for toxicity. The International Working Group standardized response criteria for MDS were used for evaluation of response. Results: Patients had a median age of 69 years (range = 44–84). All FAB subtypes were represented (RA = 16, RARS = 6, RAEB = 5, CMML = 8, RAEB-t = 6). The mean International Prognostic Scoring System score was 1.3 and ranged from 0–3.5.. The overall response rate was 63% (26/41): CR = 7% (3/41), PR = 20 % (8/41), major hematological improvement (MHI) = 29% (12/41), and minor hematological improvement (mHI) = 7% (3/41). The response rates did correlate with FAB subgroup or IPSS score. Treatment was well tolerated. The most common side effects were nausea, vomiting, diarrhea and cytopenia. Conclusions: Azacitidine appears to be effective and well tolerated in patients with MDS with marrow fibrosis. Results of this study demonstrate a response rate similar to that reported in previous studies treating MDS regardless of marrow histology. There does not appear to be a material difference in response to AZA between MDS patients with and without marrow fibrosis. [Table: see text]
Risk of Developing Rheumatoid Arthritis in Adults with Asthma: A Population-Based Case-Control Study
Authors: Mary C. Rolfes, Youn Ho Shin, Chung I. Wi, Cynthia S. Crowson, Richard S. Pendegraft, Euijung Ryu, Young J. Juhn
Journal: Journal of Allergy and Clinical Immunology (2016)
Effect of Polyinosinic-Polycytidylic Acid on Induction of Primary or Transplanted Tumors by Chemical Carcinogen or Irradiation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J. K. Ball, J. A. McCarter
Journal: JNCI Journal of the National Cancer Institute (1971)

Prolonged treatment with polyinosinlc-polycytidylic acid (poly I:C), begun 12 hours before administration of carcinogen, increased thymic lymphomas induced by a single neonatal injection of 7,12-dimethylbenz[a]anthracene (DMBA). By 150 days all mice treated with DMBA and poly I : C had died with tumors, whereas at 350 days there was a 50% survival of the mice given injections of DMBA only. However, an identical course of poly I : C treatment significantly reduced the incidence of thymic lymphomas induced by a single neonatal whole-body exposure to 400 rads. Poly I:C treatment reduced the tumor incidence from 94–40%. The effect of prolonged treatment with poly I : C, begun 12 hours before transplantation, on transplanted thymic lymphomas induced by chemical carcinogen varied considerably. Whether an antitumor effect of poly l:C was obtained depended very much on the experimental conditions. The anti-tumor activity of poly I:C treatment was most pronounced when both tumor cells and poly I:C were given intraperitoneally (a 100% survival for 1 year), whereas all control animals had died of progressively growing tumors by 60 days. When poly I:C and tumor cells were given by different routes of injection, life was only slightly prolonged, or in some situations treatment with poly I:C appeared to have a slightly enhancing effect on the number of animals dying with transplanted tumors.
Phase I/II study of individualized peptide vaccines for HLA-A2/A24 positive patients with hormone-refractory prostate cancer
Authors: M. Tanaka, H. Uemura, S. Uejima, K. Fujimoto, Y. Hirao, K. Itoh
Journal: Journal of Clinical Oncology (2008)

5155 Background: Due to a lack of standard effective treatment strategies for hormone-refractory prostate cancer (HRPC), the development of new therapeutic vaccine strategies remains of considerable interest. To evaluate both the toxicicity and capability to induce immune and clinical responses, a phase I/II study of MHC class-I restricted peptide vaccination was carried out in patients with HRPC. Methods: 23 HRPC patients positive for human leukocyte antigen (HLA)-A2 and/or -A24 were enrolled in this study. We prepared 32 kinds of 9mer peptides as HLA-A2 vaccines and 25 kinds of 9mer peptides as HLA-A24 vaccines. To select vaccine candidates among the 57 different kinds of peptides, we measured both peptide-specific CTL precursors and peptide-specific IgG in the patients’ pre-vaccination PBMCs and sera respectively. Based on the results of pre-vaccination CTL and IgG responses, positive peptides (up to 4 kinds) were individually selected for each patient and patients were vaccinated subcutaneously with each of the selected peptides emulsified with IFA at 2 weeks interval. Toxicity assessment, immunological and clinical responses were investigated every 3 months. Results: Although most patients developed grade 1 or 2 local skin reaction at the injection site, overall peptide vaccinations were well tolerated. Augmentation of peptide-specific CTLs or peptide-reactive serum IgG was observed in approximately 70 % of the patients, and serial increase of specific CTL responses was observed thereafter. Four patients showed declines of serum PSA level from the baseline, of these one achieved a complete PSA response (from 167 to 1.7 ng/ml) with partial response of bone metastasis and maintained for 13 months by vaccination monotherapy. Another patient showed partial PSA response (from 550 to 123 ng/ml) with profound shrinking of lymph node metastases and prostate. Over all median survival was 20.0 months. Conclusions: These results suggest that individualized peptide vaccination is safe and beneficial for HLA-A2/ A24 positive HRPC patients. No significant financial relationships to disclose.
Lack of MG53 in human heart precludes utility as a biomarker of myocardial injury or endogenous cardioprotective factor
Authors: Frances A. Lemckert, Adam Bournazos, Daniel M. Eckert, Manuel Kenzler, Joanne M. Hawkes, Tanya L. Butler, Bradley Ceely, Kathryn N. North, David S. Winlaw, Jonathan R. Egan, Sandra T. Cooper
Journal: Cardiovascular Research (2016)

Mitsugumin-53 (MG53/TRIM72) is an E3-ubiquitin ligase that rapidly accumulates at sites of membrane injury and plays an important role in membrane repair of skeletal and cardiac muscle. MG53 has been implicated in cardiac ischaemia-reperfusion injury, and serum MG53 provides a biomarker of skeletal muscle injury in the mdx mouse model of Duchenne muscular dystrophy. We evaluated the clinical utility of MG53 as a biomarker of myocardial injury.We performed Langendorff ischaemia-reperfusion injury on wild-type and dysferlin-null murine hearts, using dysferlin deficiency to effectively model more severe outcomes from cardiac ischaemia-reperfusion injury. MG53 released into the coronary effluent correlated strongly and significantly (r = 0.79-0.85, P < 0.0001) with functional impairment after ischaemic injury. We initiated a clinical trial in paediatric patients undergoing corrective heart surgery, the first study of MG53 release with myocardial injury in humans. Unexpectedly, we reveal although MG53 is robustly expressed in rat and mouse hearts, MG53 is scant to absent in human, ovine, or porcine hearts. Absence of MG53 in 11 human heart specimens was confirmed using three separate antibodies to MG53, each subject to epitope mapping and confirmed immunospecificity using MG53-deficient muscle cells.MG53 is an effective biomarker of myocardial injury and dysfunction in murine hearts. However, MG53 is not expressed in human heart and therefore does not hold utility as a clinical biomarker of myocardial injury. Although cardioprotective roles for endogenous myocardial MG53 cannot be extrapolated from rodents to humans, potential therapeutic application of recombinant MG53 for myocardial membrane injury prevails.
Prediction of response to alkylator-based chemotherapy in metastatic melanoma (MM) using gene expression and promoter methylation signatures
Authors: H. A. Tawbi, S. Buch, P. Pancoska, Y. Lin, M. Saul, M. Romkes, R. Sobol, J. M. Kirkwood
Journal: Journal of Clinical Oncology (2009)

9009 Background: Temozolomide and dacarbazine (TMZ and DTIC) remain the mainstay of alkylator-based chemotherapy for MM, despite response rates of 10–15% and the absence of any impact on survival. Classification of patients according to responsiveness can guide the individualization of therapy and inform approaches to abrogate mechanisms of chemotherapy resistance. Epigenetic mechanisms play an important role in regulation of genes associated with resistance and were evaluated in tandem with gene expression profiling in biological samples from MM patients (pts) to refine our understanding of the epigenomic-genomic-phenotypic interplay. Methods: We examined promoter methylation and gene expression in tumor tissues of 21 pts with MM treated with TMZ or DTIC, using high throughput technologies (Illumina Inc). The cases were divided into responder (R) and non-responder (NR) groups based on clinical response. The data were analyzed using Prediction Analysis of Microarrays (PAM) from BRB array tools. Results: Differential promoter methylation analysis revealed that 63.6% of promoter sites were hypomethylated in tumors obtained from R pts (p&lt;0.0001). PAM analysis of gene expression data revealed that a classifier set consisting of 82 genes was able to predict NRs from Rs with 83% sensitivity and 89% specificity. Promoter methylation profiling did not independently correlate with R status. A simultaneous analysis of the promoter methylation and gene expression values first stratified into 3 data-driven categories and then combined into a 3 by 3 matrix allowed us to identify a common gene expression/methylation signature of 15 genes that classified both NR and R groups accurately 100% of the time. Conclusions: Gene expression signatures independently predict response to chemotherapy in MM, however promoter methylation profiling alone does not. Analysis of combined gene expression and promoter methylation in a well- annotated clinical data set dichotomized according to response identified a highly predictive signature. The findings from this study are qualified by the relatively small sample size and are currently being validated in an expanded sample set. Supported in part by the ECOG Paul Carbone, MD, Fellowship Award. No significant financial relationships to disclose.
Conventional radiation (RT) with daily carboplatin (Cb) compared to RT alone after induction chemotherapy (ICT) [vinorelbine (Vr)-cisplatine (P)]: Final results of a randomized phase III trial in stage III unresectable non small cell lung (NSCLC) cancer. Study CRG/BMS/NPC/96 of the French Lung Cancer Study Group FNCLCC and IFCT
Authors: R. Gervais, A. Ducolone, T. Lechevalier, A. Legroumellec, E. Lemarie, E. Quoix, C. Le Pechoux, E. Bardet, M. Henry-Amar, J.-Y. Douillard
Journal: Journal of Clinical Oncology (2005)

7016 Background: Since local failure remains frequent after RT in these patients (pts), a randomized trial was designed to assess the efficacy of concurrent daily RT-Cb given after induction chemotherapy (ICT) on local control. Method: Unresectable stage III NSCLC pts (any weight loss, WHO PS 0–2, ± supraclavicular lymph node or superior vena cava syndrom) were eligible. ICT (Vr 30 mg/m2, week (w) 1, 3, 5, and 15 mg/m2, w 2, 4, 6; P 120 mg/m2 w 1 and 5) was modified (Vr 30 mg/m2 w 1 to 9; P 100 mg/m2 w 1, 5 and 9) after 1st interim analysis (190 pts accrued) due to high incidence of metastases. CR, PR, SD pts after ICT were given RT (66 Gy, 33 fractions) with (arm B) or without (arm A) daily Cb (15 mg/m2) according to randomization performed at entry (stratification on gender, PS, histology and center). Evaluation using CT scan was performed 1 month (m) after RT, every 3 m for 3 yrs, every 6 m thereafter. To demonstrate a 10% improvement on the 1-yr local control rate, 585 pts were needed (2 interim and 1 final analysis, type I error 2.21%, type II error 20%, 2-sided logrank test). Results: From June 1996 to February 2003, 291 pts were randomized to arm A and 293 to arm B. Characteristics: mean age 60; 89% men; 94% PS 0–1; 75% non squamous in women, 40% in men. Compliance to ICT was 74–85% for Vr and 92–97% for P. Response (CR + PR) rate to ICT was 46% (initial regimen), 58% (modified regimen); 194 pts received RT alone an d 233 RT+Cb. Compliance to Cb was 97%. Median survival time was 11 and 14 m in arm A and B, respectively. In ICT responders, the 1-yr local control rate was 66 vs 72% (p=.21); it was 62 vs 70% (p=.068) in the overall population. The 3-yr metastasis incidence rate was 64 and 65% in pts given initial and modified ICT. 82% pts developed grade 3–4 toxicity, mainly uncomplicated neutropenia during ICT. 8 pts in each arm had grade 3–4 esophagitis. Toxic death was more frequent in arm B (n=21) than in arm A (n=10). Conclusion: Concurrent RT+Cb does not improve significantly the 1-y local control rate in unresectable stage III NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Pierre Fabre Oncologie
Evaluation Of Potency and The Associated Biology Of The Investigational Proteasome Inhibitor, Ixazomib: Redox, Autophagic, and MAPK-Dependent Cell Death In T-Cell Lymphoma (TCL) and Hodgkin Lymphoma (HL) Cell Lines and Human Lymphoma Xenograft Models
Authors: Ravi Dashnamoorthy, Irawati Kandela, Savita Bhalla, Andrew Mazar, Andrew M Evens
Journal: Blood (2013)
Retrospective analysis of conformity with Clinical Practice Guidelines (CPGs) for elderly patients (pts) with early breast cancer
Authors: O. Trédan, I. Ray-Coquard, C. Terret, A. Lurkin, T. Bachelot, T. Philip, J. P. Droz
Journal: Journal of Clinical Oncology (2005)

8236 Background: Age-specific clinical trials demonstrate that aging does not influence the efficacy of cancer treatment, whereas age-dependent variations in care seem to persist. The aim of this study was to analyze Medical practice (Mp) in the Comprehensive Cancer Center of Lyon, and to evaluate compliance with national CPGs. Methods: Records of women ≥70 years with early breast cancer referred from 1996 to 2002 were reviewed. Tumor characteristics and medical decisions were collected. Records of 100 women were randomly selected to assess Mp compliance with CPGs. The CPGs were based on specific recommendations for elderly breast cancer pts published by the French Federation of Comprehensive Cancer Centers in 1996. Results: 318 files were analyzed. Pt median age was 75 years (range 70–90). Tumor size was the only risk factor that increased with age. Pts ≥80 years were less likely to undergo conservative surgery for tumors <30 mm (73% pts <80 years; 56% ≥80; p=0.02), axillary node dissection (80% pts <80 years; 55% ≥80; p<0.001), adjuvant radiation (85% pts <80 years; 42% ≥80; p<0.001), and chemotherapy (15% pts <80 years; 1% ≥80; p<0.001). The compliance rate with CPGs was 50%. Twenty-six percent of surgical treatments, 11% radiation therapy, 30% endocrine therapy, and 4% chemotherapy were outside the recommendations of the CPGs. Age was significantly correlated with poor compliance with CPGs (p=0.04). Conclusions: CPGs for elderly patients with early breast cancer, which have not been updated since 1996, have become inadequate with the introduction of more recent therapeutic advances. Multidimensional geriatric assessment should be integrated in the recommendations to improve conformity with CPGs. No significant financial relationships to disclose.
Melanoma recurrence patterns after positive sentinel node biopsy: A 10 year experience
Authors: T. G. Zogakis, H.-J. Wang, M. Hoban, L. J. Foshag, D. L. Morton, R. A. Essner
Journal: Journal of Clinical Oncology (2005)

7539 Background: A melanoma-positive sentinel node (SN) decreases survival and increases recurrence. Understanding recurrence patterns and their clinical impact in SN-positive patients would increase our understanding of the biology of melanoma and improve patient management. Methods: We retrospectively identified all patients who underwent SN biopsy at our institution from 1995 to 2002 and whose SN was tumor-positive. All SNs were processed by a standardized technique and stained with hematoxylin-eosin (H&E) and with immunohistochemistry (IHC) using antibodies to HMB45 and S-100. A SN was determined to be positive by H&E, IHC, or both. Survival was analyzed according to the site of recurrence. Gender, age, primary location, Breslow thickness, Clark level, histology of primary, ulceration, number of positive SNs, SN location, and number of positive non-SNs were evaluated by univariate and multivariate Cox regression analysis for their influence on recurrence. Results: Of 142 patients with tumor-positive SNs, 56 (39.4%) recurred during a median follow-up of 32 months. The most common site of recurrence was distant (47.2%) rather than nodal (24.5%) or local/intransit (28.3%). Estimated 5-year disease-free survival and overall survival for the entire group was 50 ± 5.4% and 68.5 ± 5% respectively. Two-year survival from first recurrence was 63% in patients with local/intransit recurrences, 22% in patients with nodal recurrence, and 21% in patients with distant recurrence. The difference in survival between those with distant vs. regional node (p<0.0001) vs. intransit/local (p<0.0004) recurrence was significant. On multivariate analysis age, Breslow level, number of positive SNs, and number of positive non-SNs independently significantly influenced time to recurrence. Conclusions: Older patients with thick primary melanomas and multiple positive SNs and non-SNs are at highest risk for recurrence. The most common site of recurrence is distant although nodal and local/intransit recurrences are also common. These patients require careful follow up and should be considered for adjuvant therapy. No significant financial relationships to disclose.
Be-Positive: Beyond Progression After Tyrosine Kinase Inhibitor in Egfr-Positive Non-Small Cell Lung Cancer (Nsclc) Patients. Preliminary Results from a Multicenter Italian Observational Study
Authors: T. Vavala, A. Follador, M. Tiseo, D. Galetta, A. Montanino, O. Martelli, O. Caffo, P.L. Piovano, D. Cortinovis, N. Zilembo, C. Casartelli, G. Banna, D. Colombo, M.L. Barzelloni, E. Rijavec, F.L. Cecere, E. Bria, C. Lazzari, A. Rossi, S. Novello
Journal: Annals of Oncology (2014)
Spontaneous Hepatocellular Carcinomas in Lungfish&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: P Masahito, T Ishikawa, H Sugano, H Uchida, T Yasuda, T Inaba, Y Hirosaki, A Kasuga
Journal: JNCI Journal of the National Cancer Institute (1986)

Liver tumors were observed in 2 South American lungfish (Lepidosiren paradoxa) and in 1 African lungfish (Protopterus amphibius) kept in 3 different aquariums in Japan for 2-5 years. In the first case a single, large nodule (70 X 60 X 55 mm) in the liver had been noted externally as a swelling 1 year prior to death. In the second case 2 rounded nodules (25 X 15 X 15 mm and 15 X 10 X 10 mm) were incidentally found at autopsy. In the third case, which also demonstrated abdominal swelling for 1 year preceding death, 2 green nodules (50 X 50 X 40 mm and 17 X 17 X 17 mm) were found in the liver together with multiple metastatic lesions. Histologically, variation was evident from tumor to tumor, even within the same animal. The most common histologic type was typical trabecular hepatomas. Admixtures of glandular or papillary structures were noted in some tumors. A region of poorly differentiated hepatocellular carcinoma with spindle-shaped cells in a sheetlike arrangement was noted in one case. The cause of these tumors is unknown. Since liver tumors were discovered at relatively high incidence (3/14 autopsied cases, including 6 species), lungfish seem to be predisposed to the development of liver tumors.
Brief Communication: Detection of Complement-Dependent Lytic Antibodies in Sera From Feline Leukemia Virus-Infected Cats by the Chromium-51 Release Assay 2
Authors: Chris K. Grant, Michael B. Worley, Douglas J. DeBoer
Journal: JNCI Journal of the National Cancer Institute (1977)

Sera from feline leukemia virus-infected cats lysed FL74 cells in the presence of an appropriate complement source; lysis was detected with the use of the 51 Cr release method. Serum complement from both rabbits and guinea pigs mediated lysis. Partial correlation of results was obtained from preliminary comparisons of lysis and immunofluorescence tests with the use of FL74 cells as targets.