tbuckley/cabot-search huggingface dataset:
Cause of death in patients with lower-risk myelodysplastic syndrome (MDS)
Authors: A. P. Conley, W. Stevenson, S. Pierce, J. E. Cortes, S. M. O'Brien, F. Ravandi, H. M. Kantarjian, G. Garcia- Manero
Journal: Journal of Clinical Oncology (2008)

7096 Background: We have recently developed a risk model specific for patients (pts) with lower risk MDS (Leukemia; in press) that allows the identification of poor prognosis pts. The cause of death (COD) of these pts is not well understood and relevant in view of their median age and their comorbidities. Methods: We reviewed data from 619 deceased pts with low or intermediate-1 disease by IPSS at presentation to MDACC from 1977 to 2006. Autopsy, final progress note, physician letter, or death certificate were used to determine COD. Each COD was arranged into an organ system and stratified by decade. Chi-square analysis and Kaplan-Meier log rank testing were utilized to detect differences between decades. Results: Information to determine COD was only available in 276 pts (45%). The median age at presentation was 66 years (range 19–88). The median age at time of death was 67 years (range 21–91). Overall median survival was 59 weeks (range = 1–831). An increase in median survival was noted from 1980 to 1990, 1990 to 2000, and 2000 to present (31, 57, and 79 weeks respectively, p = 0.004). A total of 88 pts (32%) transformed to AML prior to death, and the rate was stable over time (p = 0.654). By FAB classification, all subgroups were identified (RA = 114, RARS = 16, RAEB = 79, RAEB-t = 34, CMML = 33). By IPSS score, most pts were Intermediate-1 (Int-1 = 218 and Low = 58). Most pts had diploid cytogenetics (58.3%), and the most common cytogenetic abnormality was deletion of chromosome 5 (9.1%). Etiologies of infectious COD (p = 0.01) and renal COD (p = 0.003) declined over time, while hematological causes increased over each decade (p < 0.001). Other COD that were stable over time included cardiovascular, pulmonary, gastrointestinal, neurological, and oncologic causes. Sepsis (n = 40) and pneumonia (n = 39) were the most common infectious COD, but only pneumonia-related COD decreased over each decade (p = 0.003). MDS (n = 32) and AML (n = 29) were the primary hematological COD. Conclusions: This cohort of pts had a shorter median survival compared to historic controls, though median survival did improve with each decade. In addition, the most common COD has shifted over time, which may represent changes in practice. No significant financial relationships to disclose.
Abstract 13678: A Phase II Clinical Trial to Explore Various Endpoints and Their Timings for GCSF-Mobilized CD34+ Cell Therapy in No-Option Patients with Critical Limb Ischemia
Authors: Atsuhiko Kawamoto, Yasuyuki Fujita, Makoto Kinoshita, Yutaka Furukawa, Yukikatsu Okada, Yoshihiro Matsubara, Masanori Fukushima, Takayuki Asahara
Journal: Circulation (2012)
Weekly docetaxel and estramustine monophosphate (EMP) in the treatment of patients with prostate cancer and persistent/recurrent PSA elevation following primary therapy: A phase II trial of the Minnie Pearl Cancer Research Network
Authors: M. G. Mainwaring, A. A. Meluch, F. A. Greco, V. G. Gian, P. C. Kohler, A. K. Lahiry, J. G. Gandhi, L. H. Morrissey, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2004)

4759 Background: Treatment with docetaxel/EMP combinations has improved response rates in patients (pts) with hormone-refractory prostate cancer. Since a rising serum PSA level reliably detects subclinical metastases, we evaluated the feasibility, efficacy, and toxicity of weekly docetaxel and estramustine in pts with persistent or recurrent PSA elevations following primary therapy. Methods: In this phase II trial, we administered a treatment with docetaxel (35mg/m2 IV weeks 1, 2, 3) and EMP (140mg PO q 8 hours for 7 doses, beginning the evening prior to docetaxel, weeks 1, 2, 3); courses repeated every 4 weeks for 6 cycles. Eligible pts had persistent PSA elevation after primary local therapy, or rising PSA levels (without detectable metastases) following PSA normalization with primary therapy. Other eligibility criteria: ECOG PS 0–2; no previous chemotherapy; adequate organ function; informed consent. Results: Between 3/01 and 6/03, 30 pts entered this trial. Patient characteristics: median age 62 years; ECOG PS 0/1/2, 22/8/0; primary therapy: prostatectomy 12 pts (40%), prostatectomy/RT 10 pts (33%), RT alone 6 pts (20%), hormonal therapy only 2 pts (7%). 15 pts had received previous hormonal therapy. Pts received a median of 6 treatment courses (range 1 to 8). 28 of 29 evaluable pts (97%) had ≥ 75% decrease in PSA (CR 24 pts; PR 4 pts). After median follow-up of 21 months, the median, 1-year, and 2-year PFS are 14 months, 72% and 36%, respectively; 2-year overall survival is 91%. 15 pts (50%) remain in remission. Toxicity was moderate, with the following grade 3/4 toxicities: nail toxicity 3%, neutropenia 3%, fatigue 6%, N/V 10%, mucositis 3%. There were no treatment-related deaths, and no pt discontinued treatment due to toxicity. Conclusions: Treatment with weekly docetaxel/EMP produces a high PSA CR rate and is well tolerated in pts with early relapse of prostate cancer. Further evaluation of this regimen in early relapse and in the adjuvant setting is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Aventis
Abstract 19043: Rantes Dependent T Cell Recruitment into Perivascular Adipose Tissue n Angiotensin II Dependent Hypertension - Implications for Vascular Dysfunction and Blood Pressure Regulation
Authors: Tomasz Mikolajczyk, Ryszard Nosalski, Dominik Skiba, Ryszard Korbut, David Harrison, Tomasz Guzik
Journal: Circulation (2012)

Hypertension (HT) is associated with T cell activation and their recruitment into perivascular adipose tissue (PVAT). We hypothesized that RANTES chemokine is critical for T cell recruitment into PVAT and therefore plays a role in hypertension and vascular dysfunction. Thus, we cytometrically analysed numbers and phenotype of T cells infiltrating perivascular adipose tissue in C57Bl6/J and RANTES -/- mice infused for 14 days with (angiotensin II (490mg/kg/d). Results: AngII infusion caused increased PVAT leukocyte (CD45+) infiltration (2407±108 vs 654±70 cells/mg; p&lt;0.01). This increase was particularly evident for CD3+ T cells (730±38 vs 140±23 cells/mg; p&lt;0.01). Infiltration of CD4+ was higher than that of CD8+ (337±11 vs 229±11 cells/mg), but an infiltration with CD3+CD4-CD8- T cells (DN; constituting only 3-5% in blood) was particularly pronounced in pvAT (98±14 vs 23±3 cells/mg; p&lt;0.05). Expression of RANTES chemokine receptor CCR5 on PVAT T cells was increased in HT (24±09% vs 17±08%; p&lt;0.01) with highest prevalence on DN T cells and lowest on CD8+ (31±0.8% and 17±1.4%, respectively). RANTES-/- mice showed significantly decreased T cell infiltration of PVAT (394±80 vs 730±38, p&lt;0.05) which was observed in all T cell subsets suggesting that RANTES is essential for vascular T cell homing. In particular reduced content of CCR5 in T cells infiltrating perivascular adipose tissue was observed (18±1.3% vs 24±09%; p&lt;0.01). This was associated with protection of RANTES -/- from endothelial dysfunction measured as acetylocholine-induced NO dependent relaxations (p&lt;0.05 by repeated measures ANOVA). In spite of that, RANTES -/- mice still developed severe hypertension (14 day:171±8.6 mmHg vs 154±3.9 in C57Bl6/J). Importantly, we observed that angiotensin II infusion caused increased PVAT infiltration with IL-17+CD4+ cells (1.3±0.3% vs 0.2±0.2%; p&lt;0.05). This was further exacerbated in RANTES -/- mice (1.7±05% vs 1.3±0.3%). Conclusions: In hypertension, RANTES is crucial for vascular T cell homing and is a major regulator of perivascular inflammation and endothelial dysfunction. Persistent augmented presence of Th17 cells may be associated with increased blood pressure in RANTES-/-, after Ang II administration.
Randomized phase II study of carboplatin and irinotecan or irinotecan in 1–21 year old patients with refractory solid tumors
Authors: A. S. Petrilli, R. I. Jakacki, D. Perek, J. Quintana, M. Garami, H. Hussein, L. Gore, M. Messina, A. Gollerkeri
Journal: Journal of Clinical Oncology (2004)

8559 Background: Carboplatin and irinotecan have been shown to be active in pediatric tumors. Methods: The primary objective of this non-comparative, randomized study is to estimate the response rate of carboplatin AUC 4 mg/ml*min every 21 days in combination with irinotecan 12 mg/m2/day daily × 10 days every 21 days, with growth factor support (Arm A), and irinotecan 20 mg/m2/day daily × 10 days every 21 days(Arm B) in children with refractory solid tumors. The Arm A dose and schedule were determined by a prior phase I study (2003 AACR abst. #3567). One hundred and fifty-one patients were randomized and stratified by site of the primary tumor (non-CNS or CNS) and 148 were treated- 46 non-CNS and 28 CNS on Arm A, and 47 non-CNS and 27 CNS on Arm B. Non-CNS tumor types included osteosarcoma 19 (20%), rhabdomyosarcoma (RMS) 16 (17%), neuroblastoma 15 (16%), Wilm's tumor 12 (13%), sarcomas 9 (10%), retinoblastoma 5 (5%), Ewing's sarcoma 3 (3%), and others 15 (16%). CNS tumor types included gliomas (all grades) 24 (44%), medulloblastoma 10 (18%), ependymoma 9 (16%), and others 11 (20%). Results: Grade 3–4 non-hematologic toxicities in Arm A and B included infection/febrile neutropenia in 45% and 35% of patients, diarrhea in 41% and 42%, vomiting in 35% and 35%, abdominal pain/cramping in 23% and 18%, and nausea in 14% and 23%, respectively. Additional grade 3–4 non-hematologic toxicities in patients with CNS primary tumors on Arm A and B included seizures in 21% and 30% of patients, headache in 21% and 26%, ataxia in 21% and 7%, and motor neuropathy in 21% and 26%, respectively. Grade 3–4 hematologic toxicities in Arm A and B included thrombocytopenia in 20% and 3% of patients, neutropenia in 19% and 9%, and anemia in 24% and 14%, respectively. On Arm A, confirmed partial responses (PR) occurred in 2 patients (pineoblastoma and astrocytoma) and 38 patients had stable disease (SD). On Arm B, there was a confirmed complete response (CR) (neuroblastoma), and 3 PRs (RMS-2, peripheral neuroectodermal tumor). SD was noted in 35 patients. In both arms, several unconfirmed responses in evolution have been classified as SD. Conclusion: Final results will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
A twenty eight-gene signature and survival in completely-resected non-small cell lung cancer (NSCLC)
Authors: N. Van Zandwijk
Journal: Journal of Clinical Oncology (2007)

10583 Background: Current staging methods are imprecise for predicting the outcome of treatment of non-small-cell lung cancer (NSCLC). We have developed a 28-gene signature that is closely associated with recurrence-free and overall survival. Methods: We used whole-genome gene expression microarrays to analyze frozen-tumor samples from 174 patients (pT1&amp;2, N0&amp;1, MO), who had undergone complete surgical resection in 5 European institutions. Randomly generated numbers were used to assign 2/3 of the samples to an algorithm training group with the remaining 1/3 set aside for independent validation. Cox proportional hazards models were used to evaluate the association between the level of expression and patient survival. We used risk scores and nearest centroid analysis to develop a gene-expression model for the prediction of treatment outcome. Leave-one-out cross validation was used to prevent model over-training. Results: 28 genes that correlated with survival were identified by analyzing microarray data and risk scores. Based on the expression of these genes, patients in training and validation groups were classified as either high (48%) or low (52%) risk. Analysis of predicted risk groups revealed significantly different survival distributions for patients in both the training set (p&lt;0.001) and independent validation set (p=0.006). Genes in our prognostic signature encode for several membrane-bound proteins with previously demonstrated involvement in cell cycle regulation and cell proliferation processes. Conclusions: Our 28-gene signature is closely associated with time to recurrence and overall survival of completely-resected NSCLC patients. [Table: see text]
Prevalence of insomnia and associated symptoms in patients with cancer
Authors: E. J. Stepanski, L. S. Schwartzberg, L. J. Blakely, D. Fu, B. V. Fortner
Journal: Journal of Clinical Oncology (2007)

9098 Background: High rates of insomnia have been reported in patients undergoing treatment for cancer. The etiology of insomnia in these patients is unknown, but may be related to psychological factors (anxiety or depression), pain, treatment-related toxicity, or other co-morbid medical conditions. Insomnia has been linked with increased rates of depression, decreased quality of life, and increased fatigue in other patient populations, and is therefore important to understand in the context of cancer. Methods: The Patient Care Monitor (PCM; Supportive Oncology Services, Memphis, TN) is a validated software package assessing oncology-related patient symptoms using a 11- point Likert scale. This instrument is administered routinely to patients at each office visit at most community oncology clinics within the Accelerated Community Oncology Research Network (ACORN). Cross-sectional patient-reported data from 11,445 consecutive patients evaluated at ACORN sites are presented here. Results: The mean age of the sample was 61.5 (±14.2; range 18–95), and 74.3% was female. 25% had received chemotherapy within the prior month. The sample size by tumor site was as follows: breast- 3,316; GU- 2,966; GI- 1,634; hematologic- 1,373; lung- 1,224; head and neck- 501; skin- 321. 55% of the pts reported trouble sleeping, with 26% describing this trouble as moderate or severe. Mean values from patient reported symptoms on the PCM are reported below. 21.9% of patients without insomnia had recent chemotherapy, compared with 27.5% of patients with insomnia who had recent therapy (p&lt;.001). Conclusions: Insomnia occurs commonly in patients with cancer, and is associated with significantly increased fatigue, pain, and depressed mood. Additional research will explore changes in insomnia over the course of treatment, and relate these to possible etiological factors. [Table: see text] No significant financial relationships to disclose.
Interaction of mitochondrial formylated peptides with formyl peptide receptor 1 in the pathogenesis of acute lung injury
Authors: David Dorward, Christopher Lucas, Mary Doherty, Gavin Chapman, Emma Scholefield, Andrew Conway-Morris, Tiina Kipari, Calum Robb, Jennifer Felton, Philip Whitfield, Christopher Haslett, Kevin Dhaliwal, Adriano Rossi
Journal: The Lancet (2016)
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Authors: di Stefano, Henry S., Dougherty, Robert M.
Journal: JNCI Journal of the National Cancer Institute (1964)

Journal Article Virus Particles in the Nerve of Remak of Chick Embryos Get access Henry S. di Stefano, Henry S. di Stefano Departments of Anatomy and Microbiology, State University of New York, Upstate Medical Center, Syracuse, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert M. Dougherty Robert M. Dougherty Departments of Anatomy and Microbiology, State University of New York, Upstate Medical Center, Syracuse, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 33, Issue 6, December 1964, Pages 921–934, https://doi.org/10.1093/jnci/33.6.921 Published: 01 December 1964 Article history Received: 27 April 1964 Published: 01 December 1964
Brain metastases (BM) in patients treated with trastuzumab for HER2 overexpressing metastatic breast cancer (MBC): Incidence and survival
Authors: J. Stemmler, S. Kahlert, W. Siekiera, M. Untch, B. Heinrich, V. Heinemann
Journal: Journal of Clinical Oncology (2005)

1568 Objective: This retrospective analysis was performed to determine the incidence of brain metastasis (BM) in patients with HER2 overexpressing metastatic breast cancer (MBC). A specific focus was the relation of BM occurrence to remission status of visceral disease during trastuzumab treatment. Methods: Patients with MBC were included in this retrospective analyses from March 2000 to May 2004. HER2 overexpression was determined by immunohistochemistry (IHC; DAKO Hercep Test). Trastuzumab was applied at a loading dose of 4mg/kg and a weekly maintenance dose of 2 mg/kg. Results: Among 136 HER2 overexpressing patients (DAKO score 3+), fourty-two patients were identified with BM during follow-up (30.9%). A negative hormone receptor expression (ER and PgR) correlated with the incidence of BM (42.8% vs 23.4%; p=0.01). There was no correlation of the development of BM with regard to tumor grading and patient age (BM 54.5 vs without BM 50 years; p=0.27). In patients who developed BM, the median interval between visceral and brain metastasis was 14 months (range, 0–69 months). At the time BM was diagnosed, 14 out of 42 patients responded to trastuzumab based treatment schedules (OR: 33.3%, 95% CI 18.5–48.2%). Tumor growth control (OR + SD) was achieved in 47.6% of patients (95% CI 31.9–63.4%). Median survival from diagnosis of BM was 13 months (range, 0–60 months). The median overall survival calculated from first diagnosis of metastasis was shorter in patients with BM (37 months) as compared to patients without BM (47 months), but this difference did not reach the level of significance (p=0.07 log rank). Conclusion: Trastuzumab is highly effective for treatment of liver- and lung metastasis in HER2 overexpressing patients, while it is apparently ineffective to treat or prevent BM. Since one third of HER2 overexpressing patients with MBC developed BM despite effective trastuzumab treatment, new treatment strategies and closer surveillance may be warranted for these patients. No significant financial relationships to disclose.
Antisense inhibition of methylenetetrahydrofolate reductase (MTHFR) reduces survival of cancer cells in vitro and in vivo
Authors: J. Stankova, R. Rozen, J. Shang, J. Sekhon
Journal: Journal of Clinical Oncology (2004)

3103 Background: Methylenetetrahydrofolate reductase (MTHFR) is an enzyme of folate metabolism that is required for methionine biosynthesis. Various cancer cell lines are methionine dependent, i.e. they have an increased requirement for methionine and cannot, in contrast to untransformed cells, generate methionine from homocysteine. Our study was undertaken to determine whether inhibition of MTHFR gene expression might decrease cancer cell survival. Methods: Phosphorothioate oligonucleotides directed against the MTHFR gene were utilized in vitro and in vivo, to assess their anti-tumor properties. As a specific target, we selected a sequence in exon 5 (EX5) of the MTHFR mRNA and, as a control (CT), we used its scrambled sequence. The anti-tumor activity was determined with oligonucleotides alone or in combination with standard chemotherapeutic agents. Results: : Colon, lung, breast, prostate carcinoma and neuroblastoma cell lines were transfected with 200–400nM of EX5 on 2–3 consecutive days. Cell numbers were decreased by 60%–80% compared to treatment with CT. The combination of EX5 with cytostatics (5-fluorouracil, cisplatin, paclitaxel) showed an additive effect: cell numbers (colon carcinoma, lung carcinoma, prostate carcinoma, respectively) were decreased by 40%–50% compared to therapy with either agent alone. In vivo, phosphorothioate oligonucleotides were administered to athymic CD1 nude mice bearing colon (SW-620) and lung (A-549) carcinoma tumors. Tumor growth in the group treated with EX5 was decreased by ∼ 40% in comparison with the group injected with CT. MTHFR protein levels in tumors were analyzed by Western blotting; the density of the MTHFR band was quantified, relative to the density of the internal control (actin). MTHFR protein levels in tumors treated with EX5 were 60% - 70% lower than those treated with CT. Preliminary results of combined therapy in vivo on A-549 tumors have demonstrated additive effects. Conclusions: Inhibition of MTHFR expression affects cancer cell survival. Oligonucleotides or small molecule inhibitors of the enzyme should be considered in cancer chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Strida Pharma Inc.
The effect of corticorelin acetate on peritumoral brain edema: An interim report of an open-label study as part of a phase III program
Authors: L. Carr, L. Mechtler, L. Recht, A. Hormigo, N. Paleologos, J. F. Alksne, E. Arenson, J. Raizer, M. G. Shulman
Journal: Journal of Clinical Oncology (2007)

9095 Background: Steroid treatment of peritumoral brain edema (PBE) in patients with malignant brain tumors (BTs) is frequently associated with debilitating steroid side effects. The investigational agent corticorelin acetate injection, a synthetic peptide identical to h-corticotropin-releasing factor (hCRF), compared favorably to dexamethasone in reducing PBE in animal models of primary or metastatic BT. Toxicology and clinical studies including a pilot study in patients with malignant BTs published in ASCO's Annual Meeting Proceedings, showed hCRF to be safe and virtually devoid of steroid side effects. Methods: Following completion of follow-up periods for one of 2 randomized, double-blind phase III trials comparing corticorelin acetate to placebo or dexamethasone, patients with primary or metastatic BTs, PBE on pre-randomized study MRIs, and Karnofsky Performance Scores =50 were enrolled in an open-label extension study in which they took 1.0 mg corticorelin acetate by subcutaneous injection bid. We tapered dexamethasone maximally as tolerated. Patients were assessed every 4 weeks. Results: Of 47 patients who received open-label corticorelin acetate for up to one year, 28 patients continue to take it. Corticorelin acetate was safe and well tolerated, with no related deaths or SAEs. Patients typically refractory to reducing steroids - including at least 5 patients &gt;55 years of age, 7 patients with recurrent brain tumor, and 11 patients in whom prior attempt(s) to reduce dexamethasone had been unsuccessful – reduced dexamethasone with improvement or resolution of steroid side effects. We will present data in the first 30 patients to take corticorelin acetate for at least 12 weeks [the largest and longest-treated group reported to date] including changes in steroid side effects correlated with net cumulative changes in dexamethasone, and treatment-emergent AEs. Conclusions: This interim analysis supports corticorelin acetate's long-term safety, tolerability, and steroid-sparing potential. The outcome of the ongoing randomized trials may determine whether this innovative agent leads to fundamental changes in the management of PBE in patients with primary or metastatic BTs. [Table: see text]
Book: Evidence Based Practice in Primary Care
Authors: N. Donner-Banzhoff
Journal: BMJ (1999)

Eds Chris Silagy, Andrew Haines BMJ Books, £25, pp 198 ISBN 0224 06 0309 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Will the age of textbooks be over soon? Maybe, and, if so, this is the kind of book that is going to replace them. It's all about how to find, evaluate, manage, and apply information relevant to practice. The 26 authors—mainly from the United Kingdom but also from Australia, Canada, Israel, the Netherlands, and Norway—describe the logical steps from the definition of a clinical question, the search for pertinent information, critical appraisal, and applying … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif