tbuckley/cabot-search huggingface dataset:
Preliminary results of a dose-finding study of PTK787/ZK222584 (PTK/ZK) in combination with weekly vinorelbine (V) and trastuzumab (T) as treatment of patients (pts) with metastatic breast cancer (MBC) overexpressing HER-2/neu, previously treated with at least one line of chemotherapy (CT)
Authors: R. Sarmiento, A. V. Lonoce, F. Salerno, F. Cacciamani, M. R. D’Andrea, F. Torino, M. Lucia, G. Filippelli, M. Lucia, G. Gasparini
Journal: Journal of Clinical Oncology (2008)

14672 Background: Overexpression of HER2 in human cancer is related with increased expression of vascular endothelial growth factor (VEGF). Trastuzumab (T), anti-HER2 antibody, inhibits tumor growth and VEGF expression. Combination of vinorelbine (V), and T is an active 2nd-line treatment for MBC pts. PTK/ZK is a potent, selective, active inhibitor of VEGF-R TK. The blockade of HER2 receptor and VEGFR may result in superior antitumor efficacy. Methods: We have designed a dose-finding study testing the combination of V, T, and PTK/ZK in HER-2/neu + MBC pts. 1ary objective of the study: MTD of the combination. 2ary objectives: safety, pharmacokinetics (PK) and activity; study design based on 4 dose levels (DL): V from 20 to 30 mg/mq (d 1–8-15, q 28), PTK/ZK from 500 mg/daily to 1250 mg/daily. 10 pts have been enrolled so far, 9 assessable for safety. Results: First 3 pts were treated according to the study design; no DLT was found; 3 more pts were enrolled at the 2nd DL and no DLT was also found. Also the 3rdDL has been completed and no DLT has been found. Combination therapy has generally been well tolerated: nausea G1 (2/9), muscoloskeletal diffusal pain G1 (2/9), pruritus G1 (1/9), non febrile neutropenia G4 lasting less than 7 days in 3/9 patients (44.4%). One patient enrolled at the first dose level (11.1%), experienced a worsening of preexisting blood hypertension, requiring adaptation of specific medical therapy. No G3-G4 gastrointestinal toxicity has been recorded. Good responses have been observed, and are here reported. Three of 9 patients (33.3%) have completed 8 planned cycles. Eight patients (89%) are evaluable for response. Reponses observed: 5 stable disease (62.5%), 2 complete response (25%). The clinical benefit is 88.00%. PK analysis is also being conducted, by collecting blood samples on days 15 and 18 of the cycle 0 (V and T alone), and on days 14, 15 and 18 of the 1st cycle (V, T, and PTK/ZK). Conclusions: The PK analysis of both V and PTK/ZK is centralized and is ongoing. No significant financial relationships to disclose.
A multicenter, multinational retrospective analysis of mitomycin C (MMC) in refractory metastatic colorectal cancer (mCRC).
Authors: R. Ferrarotto, K. K. Machado, M. P. Mak, V. A. Vieira, T. K. Takahashi, D. F. Saragiotto, S. Kopetz, M. J. Overman, P. M. Hoff
Journal: Journal of Clinical Oncology (2011)

3577 Background: A considerable number of mCRC patients (pts) who progress on standard treatment with 5-fluorouracil (5FU), oxaliplatin, irinotecan and monoclonal antibodies still have good performance and desire further treatment. MMC has been widely used in this situation, and despite good tolerability, there is no agreement on its role. Methods: In order to assess the activity of MMC in the refractory mCRC setting, we retrospectively evaluated 109 heavily pre-treated pts who received MMC as single agent or in combination for mCRC at three different institutions. Results: Of the 109 pts, 30 (27.5%) were treated at M. D. Anderson Cancer Center (USA); 55 (50.5%) at Hospital Sírio Libanês (Brazil) and 24 (22%) at Instituto do Câncer de São Paulo (Brazil). Median age was 54 years old, 57% were male and 94% were performance status ECOG 0 or 1 at diagnosis. MMC was used in second-line in 11%, third-line in 37.6% and fourth-line or beyond in 51.4% of pts. Median TTF on the regimen prior to MMC therapy was 3.7 months. 42% received MMC as single agent while 58% received MMC combinations, mainly with fluoropyrimidines (49%). Severe toxicity was rare (1.8%), with dose reductions in 6.4% of pts. Clinical benefit with MMC, defined as improved symptoms by clinician assessment, was 12%. By response criteria, no radigraphic responses were seen. Median survival was only 4.6 months (95% CI of 4.1 to 5.5). Conclusions: This retrospective data represents the largest reported series of refractory mCRC patients treated with MMC. There were no patients with radiographic response and the low clinical benefit rate is not consistent with an active regimen. The median survival of 4.6 months is similar to the median survival expected for best supportive care in the refractory setting (4.5 months). This lack of activity strongly suggests that mitomycin should not be used in refractory mCRC.
Secular Trends of Cerebellar Gliomas in Children2
Authors: A. Fulchiero, K. Winston, A. Leviton, F. H. Gilles
Journal: JNCI Journal of the National Cancer Institute (1977)

Temporal changes in the histologic composition of cerebellar gliomas were examined in a population of 132 children operated on between 1927 and 1968 at The Children's Hospital Medical Center of Boston. Linear trends with time were examined for clinical features, histologic features, and tumor types. We found evidence of an increasing occurrence of glioma A and its associated features during the 41-year study period. This tumor type is associated with a good prognosis and is histologically well defined. Glioma B, a tumor type associated with a poor prognosis, was relatively stable with respect to time and, therefore, differed markedly from glioma A. Foci of oligodendroglia, a glioma A feature, clustered by year of surgery within a relatively short time span. This feature had a survival rate and a male sex proportion quite different from those of the other histologic features investigated.
Phase Ib study of cediranib in combination with daily temozolomide and radiation in patients with newly diagnosed glioblastoma
Authors: A. S. Chi, E. R. Gerstner, A. F. Eichler, H. K. Chea, J. Drappatz, P. Y. Wen, S. P. Ivy, J. S. Loeffler, A. G. Sorensen, R. K. Jain, T. T. Batchelor
Journal: Journal of Clinical Oncology (2009)

e13010 Background: Pre-clinical evidence suggests antiangiogenic therapy combined with radiation therapy (RT) and chemotherapy may improve tumor control in patients with glioblastoma (GBM). We conducted a phase Ib study to evaluate the safety and maximum tolerated dose (MTD) of the combination of cediranib, a potent pan-VEGF receptor tyrosine kinase inhibitor, standard RT, and temozolomide (TMZ) in patients with newly diagnosed GBM who were not taking enzyme-inducing antiepileptic drugs (EIAED). Methods: After undergoing tumor biopsy or resection, six patients with pathologically confirmed GBM were treated with concurrent TMZ (75mg/m2/day), RT (60 Gy) and cediranib (dose level 1 = 20mg/day; dose level 2 = 30mg/day) followed by post-radiation TMZ (150–200 mg/m2 on days 1–5 of each 28 day cycle) and cediranib (45mg/day) for up to 6 monthly cycles. Cediranib was started concurrently with RT and TMZ 14–21 days after surgery. Results: Six patients were treated (cediranib 20mg = 3 patients; cediranib 30mg = 3 patients). No patients experienced a DLT, establishing the MTD for cediranib in combination with RT and TMZ as 30mg/day in this patient population. Expected toxicities of hypertension, fatigue, and palmar/plantar erythema were observed. During combined cediranib and TMZ therapy in the post-radiation setting, one patient discontinued cediranib because of toxicity (grade 3 transaminase elevation) and one patient required dose reduction to 15mg/day due to grade 3 proteinuria. No intratumoral or intracerebral hemorrhages were observed during the course of cediranib treatment. No cases of wound infection or wound dehiscence were observed. All patients are alive with a median follow-up of 156 days. Conclusions: Cediranib given in combination with standard RT and TMZ for newly diagnosed GBM patients not on EIAEDs is well tolerated and the MTD is 30mg/day. The phase II component of this trial is underway and will include correlative biomarker and MRI studies. [Table: see text]
포스터전시 : 집단생활하는 경찰부대의 A형간염 유행발병을 통한 A형간염 바이러스의 독력 및 현증 발현율 연구 (초)
Authors: 현희재, 박소연, 최순욱, 안주영, 조재현, 유지원, 정준오
Journal: Clinical and Molecular Hepatology (2010)
Incidence of Lymphocytic Nuclear Projections in Bovine Lymphosarcoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Janice M. Miller, Lyle D. Miller, Kenneth G. Gillette, Carl Olson
Journal: JNCI Journal of the National Cancer Institute (1969)

Tumors from 28 cattle with lymphosarcoma were examined with the electron microscope (or the presence of nuclear projections. Numerous projections were found in tumor cells of 21 cattle with the “adult” form and in 1 of 2 cattle with the “adolescent thymic” form of the disease. Projections were not found in tumor cells of 5 cattle with the “calf” form. Blood lymphocytes from 19 cattle with lymphosarcoma were also examined for projections. They were numerous in 1 “adolescent thymic” and 16 “adult” cases, but were absent in 2 cases of the “calf” form. Nuclear projections were relatively rare in lymph nodes and peripheral lymphocytes from apparently normal control cattle. In a multiple-case herd, circulating lymphocytes with nuclear projections were common in 12 cows with lym-phocytosis and in 3 of 7 suspects, but infrequent in 7 cows with normal lymphocyte counts. The relative frequency of projections was also increased in 9 of 17 cattle which had been inoculated in utero with tumor or blood from animals with lymphosarcoma.
Microscopical Diagnosis of Olfactory Esthesioneuromas: General Review and Report of Five Cases
Authors: Remi Gerard-Marchant, Christian Micheau
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Microscopical Diagnosis of Olfactory Esthesioneuromas: General Review and Report of Five Cases Get access Remi Gerard-Marchant, M.D., Remi Gerard-Marchant, M.D. Laboratory of Histopathology, Institut Gustave-Roussy, Villejuif (Seine), France Search for other works by this author on: Oxford Academic PubMed Google Scholar Christian Micheau, M.D. Christian Micheau, M.D. Laboratory of Histopathology, Institut Gustave-Roussy, Villejuif (Seine), France Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 35, Issue 1, July 1965, Pages 75–82, https://doi.org/10.1093/jnci/35.1.75 Published: 01 July 1965 Article history Received: 01 December 1964 Published: 01 July 1965
Review of Wesley J. Smith,<i>Secondhand Smoke</i><sup>1</sup>
Authors: Stephen R. Latham
Journal: The American Journal of Bioethics (2009)

Secondhand Smoke (“SHS”) is the personal blog of Wesley J. Smith, outspoken author of a dozen books including Forced Exit: Euthanasia, Assisted Suicide and the New Duty to Die (2006), Culture of De...
Phase I study of bortezomib plus cetuximab in patients with tumors expressing epidermal growth factor receptor (EGFR)—Final report
Authors: O. N. Pandey, E. Greeno, A. Z. Dudek
Journal: Journal of Clinical Oncology (2008)

19030 Background: Bortezomib is a proteasome inhibitor that augments EGFR inhibitor activity. Cetuximab is a mouse-human antibody against EGFR that has been found to induce tumor responses in patients with colon cancer and head and neck cancer. The purpose of this study was to establish a maximum tolerated dose (MTD) for the combination of bortezomib plus cetuximab in patients with EGFR-expressing epithelial tumors. Methods: A 21-day treatment cycle was given with a maximum of six cycles per patient. Bortezomib was administered intravenously on days 1 and 8. Dose escalation consisted of eight dose levels beginning with a minimum bortezomib dose of 1.3 mg/m2 and increasing in one-tenth increments to 2.0 mg/m2. Cetuximab was delivered with an initial dose of 400mg/m2 on day 1 cycle 1, followed by a dose of 250mg/ m2 on days 8 and 15. For subsequent cycles, cetuximab was delivered at a dose of 250mg/ m2 on days 1, 8 and 15. Results: Thirty-one patients (19 male and 12 female) with an ECOG PS <2 were enrolled in this study from November 2005 to September 2007. The median age was 56 (range 31–68). Median number of prior chemotherapy regimens was 3 (range 0–7). Primary tumor sites included lung (13), head and neck (6), kidney (4), pancreas (3) bladder (2), skin (1), esophagus (1) and ovary (1). A total of 88 cycles were administered, with a median number of cycles per patient of 2 (range 1–6). One dose-limiting (DLT) grade 3 gastrointestinal (CTCAE 3.0) toxicity was seen at dose level 4. No further grade 3 or 4 toxicity was observed at dose level 4 or higher doses. Grade 3 or 4 toxicities included mucositis (n=1), back pain (n=1), carotid artery hemorrhage (n=1), flu-like syndrome (n=1), fatigue (n=5), dehydration (n=3), elevated creatinine (n=1), electrolyte abnormalities (n=2), gastrointestinal (n=6), cellulitis (n=2), muscle weakness (n=1), dyspnea (n=3), pulmonary embolism(n=1), neuropathy (n=1), syncope (n=1), hypotension (n=1) and bacteremia (n=1). Conclusions: MTD for bortezomib plus cetuximab was not achieved at the highest dose levels of bortezomib tested. This regimen has shown moderate clinical activity as measured by progression free survival in extensively pretreated patients with non-small cell lung cancer and warrants further investigation. No significant financial relationships to disclose.
Diagnosing liver metastases: a Bayesian analysis.
Authors: S E Lind, D E Singer
Journal: Journal of Clinical Oncology (1986)

Clinicians frequently perform tests to determine whether patients have liver metastases. Optimal use of a laboratory test requires that the clinician know the test's operating characteristics (its sensitivity and specificity) and have an estimate of the pretest probability that disease is present. We have surveyed studies that examined the value of four biochemical and three imaging tests in establishing a diagnosis of hepatic metastases in patients who underwent an invasive procedure to establish the presence or absence of disease. We have pooled the data from these studies to arrive at values for the sensitivity and specificity of each of these tests, and calculated the predictive values for these tests over a wide range of pretest probabilities of disease. Several examples illustrate how this information may be used clinically. We provide a framework for the optimal interpretation of these commonly ordered tests and indicate the data needed for their complete analysis.
City of Hope's referring physician communication process improvement initiative.
Authors: Joseph C. Alvarnas, Priscilla Avanessian, Mark Tsuneo Wakabayashi, Tricia Kassab, Alexandra M. Levine
Journal: Journal of Clinical Oncology (2013)

63 Background: City of Hope’s (COH) Performance Excellence Program (PEP), a physician incentive program aimed at improving quality and process outcomes, identified the need to establish a process for strengthening COH’s relationship with referring physicians. Methods: Working in collaboration with New Patient Services, Marketing, and physicians across multiple disciplines, we implemented a manual process of copying information in all H and Ps/Admit Notes, discharge summaries, consultation notes, and operative reports to referring MDs if the COH MD had not done so. The PEP team is also in the process of establishing a specific COH referral MD line that would allow for priority queuing and a real-time warm transfer to the MD/ MD’s office. Marketing of the number will be conducted through a standard thank-you cover letter sent by every COH MD upon initial consultation of patient, as well as through a newly revamped physician website. The implementation of a Health Information Exchange is also in progress. Results: Overall satisfaction on COHs ability to communicate increased from 23% to 30%. Number of 10 or more updates received from COH increased from 0% to 17%. Those who referred 20% of their patient volume increased from 15% to 20% while those who only referred 1-5% decreased from 69% to 30%. Conclusions: Through the multiple strategies and joint efforts across disciplines, COH has strengthened its relationship with referring MDs and increased its referral volume. [Table: see text]
Extracellular Signal-Regulated Kinase Mediates Stimulation of TGF-β1 and Matrix by High Glucose in Mesangial Cells
Authors: MOTOHIDE ISONO, M. CARMEN IGLESIAS-DE LA CRUZ, SHELDON CHEN, SOON WON HONG, FUAD N. ZIYADEH
Journal: Journal of the American Society of Nephrology (2000)

Abstract. High ambient glucose exerts its injurious effects on renal cells through nonenzymatic and enzymatic pathways, including altered signal transduction and upregulation of the transforming growth factor-β (TGF-β) system. Extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase (MAPK) cascade, is activated in mesangial cells cultured in high glucose and in glomeruli of diabetic rats. However, the biologic consequences of ERK activation in the kidney have not been investigated. To clarify the role of ERK activation, mouse mesangial cells were exposed to normal (5.5 mM) or high (25 mM) glucose with or without addition of PD98059, a specific inhibitor of MAPK/ERK kinase (MEK), an upstream kinase activator of ERK. Cells that were exposed to high glucose exhibited significant increases in ERK activity, TGF-β1 expression (total protein, mRNA levels, and promoter activity), [3H]-proline uptake, and α1(I) collagen and fibronectin mRNA levels. Treatment with PD98059 (up to 25 μM) significantly inhibited these parameters. In contrast, 25 μM PD98059 had no significant effect on any of the parameters measured in cells that were exposed to normal glucose. Overexpression of MAPK phosphatase CL 100 prevented TGF-β1 promoter activation by high glucose, confirming the involvement of the MEK-ERK pathway in response to high glucose. The conclusion is that activation of ERK in mesangial cells is responsible for high-glucose-induced stimulation of TGF-β1 and contributes to the increased extracellular matrix expression.
Association of CD4 lymphopenia with survival in patients with advanced cancer.
Authors: J. Peron, I. L. Ray-Coquard, S. I. Labidi-Galy, P. Heudel, G. Clapisson, P. A. Cassier, I. Philip, C. Borg, O. Tredan, T. D. Bachelot, C. Sebban, H. Ghesquieres, C. Menetrier-Caux, C. Caux, P. Biron, J. Blay
Journal: Journal of Clinical Oncology (2011)

e21145 Background: Lymphopenia (lyp) is associated with an increased risk of toxicity and early death after cytotoxic chemotherapy (CT) in cancer patients (pts) and is also a prognostic factor for overall survival (OS) and progression free survival (PFS) in lymphoma, breast, and sarcoma pts. We report here the impact of CD4 lyp on patient survival after 10 years. Methods: 220 HIV negative pts treated in 2C dept in the Centre L.Bérard (Lyon, France) were included in this study from 04/99 to11/00. 98 (45%) had lymphoma or myeloma, 58 (26%) sarcoma, 21 (9%) breast cancer and 43 (19%) for other cancers. Two groups of diseases: 1) chemocurable diseases (NHL or germ cell tumors), 2) seldom chemocurable disease (advanced carcinomas and sarcomas). Phenotypic analysis of peripheral blood lymphocyte (ly) subsets on d1 of CT was determined using flow cytometry. Prognostic factors were analyzed univariate and multivariate analysis using Cox model. Results: With a minimum follow-up of 10 years in the entire group, age>60, PS >1, stage, tumor type, baseline ly <700/uL, CD4 count<450/uL CD8<400/uL correlated to OS in univariate analysis. Using Cox model, age, PS, stage, tumor type, use of high-risk CT, and ly subsets independently correlated to OS. In lymphoma pts, baseline ly count<700/uL, CD4 count<450/uL, CD56 count <100/uL were independent prognostic factors for OS and PFS using Cox model. In sarcoma pts, baseline ly count <700/uL, CD4 count <450/uL and CD8 count <400/uL were independent risk factors for OS and PFS in multivariate analysis. In pts with seldom chemocurable diseases (advanced carcinomas and sarcomas), all pts with total ly < 400/ uL or CD4 ly < 200/ uL died within 18 months (median: 6 mos). In lymphoma and germ cell tumor pts, all pts but one with ly< 200/ uL or CD4 lymphocytes < 100/ uL relapsed and died. Conclusions: Peripheral blood lymphocyte subsets prior to initiation of CT is a strong predictor of OS and PFS in this series. All pts with advanced breast carcinoma or sarcoma and CD4 count<200/uL had a very short term survival.
P-007 The validation study of tissue specimen for limitation of endoscopic submucosal dissection indication criteria in gastric cancer
Authors: H.S. Choi, H.J. Chun, I.K. Yoo, J.M. Lee, S.H. Kim, E.S. Kim, B. Keum, Y.T. Jeen, H.S. Lee, C.D. Kim
Journal: Annals of Oncology (2015)
Phase II trial of radiosurgery (RS) for 1 to 3 newly diagnosed brain metastases from renal cell, melanoma, and sarcoma: An Eastern Cooperative Oncology Group Study (E6397)
Authors: R. R. Mañon, A. Oneill, M. Mehta, J. Knisely, M. Werner-Wasik, H. Lazarus, H. Wagner, M. Gilbert
Journal: Journal of Clinical Oncology (2004)

1507 Background: Whole brain radiation therapy (WBRT) is considered standard therapy for patients (pts.) w/ brain metastasis. Long term survivors are at risk for CNS morbidity, and the value of low doses of WBRT in radioresistant tumors is suspect. RS emerged as a treatment modality, and retrospective analyses found no difference in survival when RS is given up front. Prior to evaluating RS w/ delayed WBRT in a Phase III trial, the feasibility of RS alone was prospectively tested in this phase II trial. Methods: Pts. w/ histologically confirmed renal cell carcinoma, melanoma, or sarcoma, w/ 1–3 brain metastases, ECOG performance status (PS) of 0–2, and no previous cranial RT were enrolled. Exclusion criteria were: leptomeningeal disease; metastases in medulla, pons, or midbrain; multiple liver metastases. Based on tumor size, pts. received 24, 18, or 15 Gy RS dose. At recurrence, treatment was at the discretion of treating physicians. Results: Between 7/98 and 8/03, 36 pts. accrued; to date, 32 eligible by entry criteria; 28/32 were male and the median number of lesions was 1. ECOG PS was: 44% PS 0; 34% PS 1; 19% PS 2. With median F/U of 25 mo., median survival (MS) was 8.3 mo. (95% CI 6.8–13.7); 22/ 32 pts. died, 7/22 (32%) from CNS death; 3% had PR, 34% had stable disease, 41% had PD, and 13% were unevaluable (scans not performed). Three and 6 month in-field failures were 28 and 45% (includes simultaneous failures in-field and outside field), and failure rates outside the radiosurgery volume at 3 and 6 months were 4 and 17%. There were 3 ≥ grade 3 CNS toxicities, possibly related to RS. Conclusions: In this study, MS was equivalent to published surgical and concurrent RS +WBRT series and better than WBRT alone. Failures outside RS field were low and treatment was well tolerated. Response rates and failures w/ in the RS volume were higher than historic controls. Delaying WBRT may be appropriate for some subgroups of patients w/ radioresistant tumors, but failures beyond 6 mo. have not been addressed yet. Based on these results, a phase III randomized study evaluating the RS alone in some subsets of patients is warranted. No significant financial relationships to disclose.