tbuckley/cabot-search huggingface dataset:
Value of different modalities of granulocyte-macrophage colony-stimulating factor applied during or after induction therapy of acute myeloid leukemia.
Authors: B Löwenberg, M A Boogaerts, S M Daenen, G E Verhoef, A Hagenbeek, E Vellenga, G J Ossenkoppele, P C Huijgens, L F Verdonck, J van der Lelie, J J Wielenga, H C Schouten, J Gmür, A Gratwohl, U Hess, M F Fey, W L van Putten
Journal: Journal of Clinical Oncology (1997)

PURPOSE The hematopoietic growth factors (HGFs) introduced into induction chemotherapy (CT) of acute myeloid leukemia (AML) might be of benefit to treatment outcome by at least two mechanisms. HGFs given on days simultaneously with CT might sensitize the leukemic cells and enhance their susceptibility to CT. HGFs applied after CT might hasten hematopoietic recovery and reduce morbidity or mortality. MATERIALS AND METHODS We set out to evaluate the use of granulocyte-macrophage colony-stimulating factor (GM-CSF; 5 microg/kg) in a prospective randomized study of factorial design (yes or no GM-CSF during CT, and yes or no GM-CSF after CT) in patients aged 15 to 60 years (mean, 42) with newly diagnosed AML. GM-CSF was applied as follows: during CT only (+/-, n = 64 assessable patients), GM-CSF during and following CT (+/+, n = 66), no GM-CSF (-/-, n = 63), or GM-CSF after CT only (-/+, n = 60). RESULTS The complete response (CR) rate was 77%. At a median follow-up time of 42 months, probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years were 38% and 37% in all patients. CR rates, OS, and DFS did not differ between the treatment groups (intention-to-treat analysis). Neutrophil recovery (1.0 x 10(9)/L) and monocyte recovery were significantly faster in patients who received GM-CSF after CT (26 days v 30 days; neutrophils, P &lt; .001; monocytes, P &lt; .005). Platelet regeneration, transfusion requirements, use of antibiotics, frequency of infections, and duration of hospitalization did not vary as a function of any of the therapeutic GM-CSF modalities. More frequent side effects (eg, fever and fluid retention) were noted in GM-CSF-treated patients predominantly related to the use of GM-CSF during CT. CONCLUSION Priming of AML cells to the cytotoxic effects of CT by the use of GM-CSF during CT or accelerating myeloid recovery by the use of GM-CSF after CT does not significantly improve treatment outcome of young and middle-aged adults with newly diagnosed AML.
Impact of emergency oral rabies vaccination of foxes in northeastern Italy, 28 December 2009–20 January 2010: preliminary evaluation
Authors: K Capello, P Mulatti, A Comin, L Gagliazzo, V Guberti, C Citterio, P De Benedictis, M Lorenzetto, C Costanzi, P Vio, P Zambotto, G Ferri, F Mutinelli, L Bonfanti, S Marangon
Journal: Eurosurveillance (2010)

Fox rabies re-emerged in northeastern Italy in 2008, in an area bordering Slovenia. In 2009, the infection spread westward to Veneto region and in 2010 to the provinces of Trento and Bolzano. Aerial emergency oral fox vaccination was implemented in the winter 2009-10. Since this vaccination was performed at altitudes below the freezing level, a statistical analysis was conducted to evaluate its impact. Of the foxes sampled following the vaccination campaign, 77% showed a rabies antibody titre of >or=0.5 IU/ml.
Probability of thrombosis of vascular access among hemodialysis patients treated with recombinant human erythropoietin.
Authors: D N Churchill, N Muirhead, M Goldstein, G Posen, W Fay, M L Beecroft, J Gorman, D W Taylor
Journal: Journal of the American Society of Nephrology (1994)

The objective was to evaluate the effect of the treatment of anemia with recombinant human erythropoietin (EPO) on thrombosis of the vascular access used for hemodialysis. The research design was a prospective cohort study comparing EPO-treated hemodialysis patients with a comparison group matched for type of vascular access, clinical center, and age. All patients commencing hemodialysis in the study centers between March 1988 and July 1991 were eligible if either a graft or fistula had been used as a first permanent vascular access. There were 64 matched fistula pairs and 38 matched graft pairs. There were more patients with a history of cardiovascular disease in the EPO group than in the comparison group for both fistulae and grafts, 34 versus 14% for the former and 37 versus 5% for the latter. There was no difference between EPO and comparison groups with respect to time to first thrombosis of fistula, 11.3 versus 10.6%, respectively, by thrombosis of grafts among those treated with EPO--33.6 versus 11.2% (P = 0.02). EPO treatment does not increase the probability of fistula thrombosis, but there is an association with an increased probability of graft thrombosis.
Pemetrexed (P) and bevacizumab (B) in patients (pts) with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Final results and correlation with TS, MTHFR, and VEGF gene polymorphisms.
Authors: A. Argiris, M. Karamouzis, W. E. Gooding, B. Branstetter, S. Zhong, L. E. Raez, P. Savvides, M. Romkes
Journal: Journal of Clinical Oncology (2010)

5533 Background: We hypothesized that B, a monoclonal antibody against VEGF, will potentiate the activity of P, a multi- targeted antifolate, in R/M SCCHN. Methods: Eligible pts had R/M SCCHN with measurable disease, good performance status (PS), no history of gross hemoptysis, and no prior systemic therapy for R/M SCCHN. Treatment consisted of P 500 mg/m2 and B 15 mg/Kg, given intravenously every 21 days, with folic acid and B12, until progression. Primary endpoint was time-to-progression (TTP). DNA was isolated from whole blood samples for the detection of polymorphisms in thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and VEGF. Results: 40 pts were enrolled. Median age 59 (36-85); male/female, 32/8; PS 0/1, 16/24; prior chemotherapy as part of curative treatment: 29; primary site: oropharynx (21), oral cavity (7), larynx (4). Median number of cycles 5.5 (1-15). In 37 evaluable pts, the overall response rate was 30% (95% CI, 19-51%) (CR: 2; PR:11; SD: 21) and disease control rate 86%. Median TTP was 4.9 months (mo) (95% CI, 2.9-6.9) and median overall survival (OS) 11.5 mo (8.8-14.2). Bleeding events >grade 2 occurred in 6 pts (15%), 4 were grade 3 and 2 fatal (1 tracheal bleeding in a pt with history of tracheal bleeding that had responded to re-irradiation; 1 recurrent tumor-related bleeding after re-challenging with B); 8 other grade 1-2 bleeding events occurred. Other serious toxicities (all grade 3): anemia (2), neutropenia (4), AST elevation (1), stomatitis (1), anorexia (1), edema (1), hyponatremia (2), hypokalemia (1), fatigue (2), infection (3); 1 pt died of sepsis after receiving 8 cycles. 28 pts were genotyped. For the MTHFR A1298C SNP, median TTP for homozygote pts with AA was 4.2 and for pts with AC or CC 7 mo (p=0.069); median OS for AA was 11 mo and for AC or CC 32.8 mo (p=0.006). The associations with other SNPs were not significant. Conclusions: P and B is a novel, efficacious non-platinum regimen in R/M SCCHN. Bleeding events were frequent but some may have been due to natural history of disease. Polymorphisms in MTHFR may offer potential for treatment individualization. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Genentech, Lilly Genentech, Lilly
GTX chemotherapy for metastatic pancreatic cancer: Response, survival, and toxicity data
Authors: R. L. Fine, D. R. Fogelman, S. Schreibman, S. Guba, J. Sharma, G. Shapiro
Journal: Journal of Clinical Oncology (2004)

4271 Background: In vitro studies in our lab demonstrated synergistic cytotoxicity with 5FUR, gemcitabine, and docetaxel (GTX) against human PC lines with mutant p53, activated ras and deleted p16. This increased Bax and decreased Bcl-XL levels by a p53 independent mechanism involving the MAPK pathway with decreased ERK phosphorylation. Methods: We performed a retrospective chart review of all identifiable patients treated with GTX by the authors. (The regimen consists of capecitabine 1000mg/m2/day total as BID doses days 1–14; on days 4 and 11 gemcitabine (750 mg/m2/IV over 75 min) and docetaxel (30 mg/m2 ) are given IV. Response rates were measured per WHO criteria; survival was dated from the first GTX treatment. Results: We treated 35 metastatic pancreatic cancer patients with GTX chemotherapy dating from 2001 onwards. 94% of patients had metastases in the liver. We did not exclude patients for poor performance status. Of these, 28 completed at least three cycles of chemotherapy and were considered evaluable for response. At the metastatic sites, there were 3 CR and 11 PR for a 50% response rate. (40% on intent-to-treat basis). At the primary tumor (n=25, 3 pts had Whipple), there were 4 CR and 6 PR for a 40% response rate (31% on intent-to-treat basis). 34% of patients were previously treated with gemcitabine based regimens. Median survival for all 35 is at least 8.6 months and 10.5 months for those who complete 3 cycles. The longest survivor is alive at 1056 days. Toxicities were mild; of 32 patients evaluated for toxicity, there were 6 grade 3–4 leukopenias; 3 grade 3–4 anemias; 5 grade 3–4 thrombocytopenias. Ten patients experienced hand-foot syndrome, 11 patients abdominal cramps, 17 patients had diarrhea. There were 2 grade 4 infections (no deaths). 14 of 18 (78%) patients with an elevated CA 19–9 had greater than a 90% drop. In general, the regimen was well tolerated by patients. Conclusions: The GTX regimen represents a potential advance in the treatment of metastatic pancreatic cancer. It demonstrates an excellent response rate and superior survival of an extremely poor prognosis group of patients. A prospective phase II trial is in progress and a phase III trial is being planned. No significant financial relationships to disclose.
Pre-existing comorbidities in patients with metastatic colorectal cancer receiving biologic treatments.
Authors: Z. Zhao, A. Z. Fu, B. Barber, S. K. Gao, G. G. Liu
Journal: Journal of Clinical Oncology (2010)

e14106 Background: Patients with mCRC often have other medical ailments that may impact treatment decisions, prognoses, and quality of care. This study was conducted to examine the pre-existing comorbidities in the newly diagnosed mCRC population receiving biologic treatments. Methods: The study used a large U.S. claims database. Patients aged ≥ 18 with newly diagnosed mCRC between 1/2005 and 6/2008 were selected using the ICD-9 diagnosis codes (CRC: 153.x [excluding 153.5], 154.0, 154.1, 154.8; distant metastasis: 196.0, 196.1, 196.3, 196.5, 197.x [excluding 197.5], 198, 199.0). The initial mCRC diagnosis date was defined as the index date. One-year continuous medical and pharmacy benefit coverage prior to the index date was required. Biologic treatments (bevacizumab, cetuximab and panitumumab) were examined after the index date. Comorbidities were examined during the 1-year period prior to the index date for each biologic treatment. Results: Based on the selection criteria, 4,126 patients were included with mean (± SD) age of 61.8 (± 11.9) years, 56% male, and 72% with the colon as the primary tumor type. Distribution of metastases included liver (52%), lung (15%), bone (4%), and brain (1%). There were 3,762, 1,300, and 129 patients who received bevacizumab, cetuximab, and panitumumab, respectively. Among those who received bevacizumab, the most prevalent comorbidity was cardiovascular disease (CVD) (57%) including hypertension (37%), arterial thromboembolism including ischemic heart disease (15%), coronary artery disease (14%), dysrhythmias (10%), venous thromboembolism (5%), and congestive heart failure (4%). 31% had a history of bleeding. Over 10% of bevacizumab patients had a major surgery, bone fracture, or open wound 30 days prior to mCRC diagnosis;. Additionally, 18% of bevacizumab patients had diabetes, 5% had renal failure or insufficiency, and 4% had skin disease. Similar pre-existing comorbidities were observed in patients who received cetuximab or panitumumab. Conclusions: Pre-existing comorbid medical conditions are common in mCRC patients subsequently treated with biologics, with CVD being the most prevalent comorbidity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen
Virus-Associated Surface Antigens on L Cells and Moloney Lymphoma Cells2
Authors: Eva Maria Fenyö, Gertrud Grundner, Eva Klein
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Virus-Associated Surface Antigens on L Cells and Moloney Lymphoma Cells Get access Eva Maria Fenyö, Eva Maria Fenyö Search for other works by this author on: Oxford Academic PubMed Google Scholar Gertrud Grundner, Gertrud Grundner Search for other works by this author on: Oxford Academic PubMed Google Scholar Eva Klein Eva Klein 3Department of Tumor Biology, Karolinska Institutet, Stockholm 60, Sweden. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 3, March 1974, Pages 743–751, https://doi.org/10.1093/jnci/52.3.743 Published: 01 March 1974 Article history Received: 24 July 1973 Accepted: 30 November 1973 Published: 01 March 1974
A phase II clinical trial of ZD1839 (gefitinib) in combination with docetaxel as first-line treatment in patients with advanced breast cancer
Authors: S. K. Dennison, S. A. Jacobs, J. Wilson, J. Seeger, T. Cescon, J. M. Raymond, C. E. Geyer, N. Wolmark, S. M. Swain
Journal: Journal of Clinical Oncology (2007)

1059 Background: We conducted a phase II multi-institutional trial of gefitinib and docetaxel as first-line treatment in patients with metastatic breast cancer. The primary objectives were to determine the clinical benefit rate (defined as the proportion of patients who experienced confirmed complete response or partial response or who had stable disease for at least 24 weeks) and the toxicity profile of the combination treatment. Methods: All patients had histologically confirmed breast cancer with metastatic disease. They may have received adjuvant chemotherapy, but no prior docetaxel or prior chemotherapy for metastatic disease. Patients received gefitinib 250 mg once daily and docetaxel 75 mg/m 2 every 3 weeks, until tumor progression, toxicity or other reasons for discontinuation. Results: Between April 2003 and September 2004, 33 patients were enrolled at 11 participating institutions. Patients received a median of 5 cycles of treatment. The clinical benefit rate was 51.5% (95% CI: 33.5% - 69.2%). There was 1 confirmed complete response and 12 confirmed partial responses, and the overall objective response rate was 39.4% (95% CI: 22.9% - 57.9%). Four patients had stable disease for = 24 weeks. The median duration of clinical benefit was 10.9 months (95% CI: 6.0 - 17.6 months). The most common reason for study discontinuation was disease progression (16 patients), followed by toxicity (10 patients). Toxicities were mainly attributable to docetaxel, including = grade 3 neutropenia in 43% of patients. Conclusion: The combination of gefitinib and docetaxel is an active regimen in patients with previously untreated metastatic breast cancer. Further work is needed to determine which subset of patients with breast cancer will benefit from gefitinib. No significant financial relationships to disclose.
Mammary Tumor Induction in Male and Female Sprague-Dawley Rats by Adriamycin and Daunomycin&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: E Bucclarelli
Journal: JNCI Journal of the National Cancer Institute (1981)

Male and female noninbred Sprague-Dawley rats 30-36 days of age were given single iv injections of 10 or 5 mg adriamycin (Ad)/kg or 10 mg daunomycin (DM)/kg. Multiple mammary tumors (MT), mostly adenocarcinomas, were observed in 29 and 67% of the females given 10 and 5 mg Ad/kg, respectively, and in 64% of those given 10 mg DM/kg. The mean induction time for females receiving 10 mg Ad/kg was 135 days, for those receiving 5 mg/kg it was 114 days, and for those receiving DM it was only 80 days. Single MT, also mostly adenocarcinomas, were observed an average of 279 days from injection in 31% of the males given 5 mg Ad/kg and an average of 91 days from injection in 37% of the males given 10 mg DM/kg. No tumors were observed in the males given 10 mg Ad/kg, but these survived for only 79 days after treatment.
Retinal toxicity after high-dose cisplatin therapy.
Authors: G Wilding, R Caruso, T S Lawrence, Y Ostchega, E J Ballintine, R C Young, R F Ozols
Journal: Journal of Clinical Oncology (1985)

Because of increasing complaints of visual dysfunction, 13 patients with refractory or recently diagnosed ovarian carcinoma were evaluated for possible cisplatin-induced ophthalmologic toxicity. All patients had received high-dose cisplatin (200 mg/m2 in five divided daily doses) over two to four cycles. Eight patients (62%) developed symptoms of blurred vision and three (23%) also developed altered color perception. Retinal toxicity in the form of cone dysfunction was documented by electroretinography and color vision testing in 11 patients. Three patients were studied prospectively. Two patients who developed cone dysfunction had normal ophthalmologic exams before the initiation of chemotherapy or after one cycle of cisplatin, suggesting a causal relationship between cisplatin therapy and subsequent retinal abnormalities. Though visual acuity improved off therapy, color vision abnormalities persisted as long as 16 months beyond therapy.
Effects of Mycophenolate Mofetil in Mercury-Induced Autoimmune Nephritis
Authors: Elena Nieto, Esther Escudero, Elena Navarro, Mari[Combining Acute Accent]a Ya[Combining Acute Accent]n[Combining Tilde]ez-Mo, Ana Marti[Combining Acute Accent]n, Guillermo Pe[Combining Acute Accent]rez de Lema, Francisco Sa[Combining Acute Accent]nchez-Madrid, Francisco Mampaso
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Mycophenolate mofetil (MMF) is a new immunosuppressive drug whose active metabolite, mycophenolic acid (MPA), blocks the action of inosine monophosphate dehydrogenase, resulting in the inhibition of the novo purine synthesis. Thus, MPA has an antiproliferative effect on T and B lymphocytes and also inhibits the glycosylation of cell surface adhesion proteins involved in cell-cell contact and in the recruitment of circulating leukocytes to sites of tissue damage and inflammation. In this study, the effect of MMF in the mercury model of nephritis was examined. Repeated exposure to HgCl2 induces an autoreactive Th2 cell subset-inducing polyclonal B cell activation in the Brown Norway (BN) rat. This leads to the development of an autoimmune syndrome characterized by synthesis of autoantibodies (mainly anti–glomerular basement membrane [GBM] Abs) with glomerular linear deposits of IgG, proteinuria, and tubulointerstitial nephritis. Results show that MMF has a preventive effect on mercury-induced disease as it blocks anti-GBM Ab synthesis, thus avoiding glomerular IgG deposits and proteinuria and the development of interstitial nephritis. However, the therapeutic effect of MMF seems to be restricted to its antiinflammatory properties blocking the extravasation of circulating leukocytes to renal interstitium by interfering with the very late activation antigen 4/vascular cell adhesion molecule–1 (VCAM-1) cell adhesion pathway. Also, MMF administration to mercury-injected rats reduces the secretion of the proinflammatory cytokine tumor necrosis factor–α. These findings confirm that MMF has a strong effect on the primary immune response in this model. Nevertheless, when the disease is in progress, MMF acts exclusively on the inflammatory response. MMF could be useful in the treatment of diseases associated with renal inflammation.
Prevention of radiation pneumonitis in breast cancer irradiation through dose-volume constraint
Authors: P. Lind, U. Blom-Goldman, M. Anderson, B. Wennberg, G. Svane
Journal: Journal of Clinical Oncology (2004)

693 Background: Previously, we have reported results on pulmonary side-effects in 481 irradiated women with breast cancer (BC). Moderate radiation pneumonitis (RP-G2) was diagnosed in 7–12 % of pat undergoing loco-regional RT. A mean reduction in vital capacity (VC) of 450 ml was found in the latter group. CT-changes correlated well with symptoms and VC-decline. The present study sought to determine whether dose-volume constraints, according to ROC-analysis from the previous study, would reduce the number of RP-G2 and the mean reduction in VC by half. We plan to accrue 120 pat undergoing loco-regional RT. Methods: The pat underwent 3-D dose planning aimed at minimizing the irradiated ipsilateral lung volume receiving > 20 Gy (V20) to < 30%. Pulmonary function testing was performed before and 5 mos. post-RT. Chest-CT was repeated 4 mos. post-RT and radiological changes compared to base-line were contoured and the mean doses in these sub-volumes were calculated. The patients were followed for signs of RP 1, 4 and 7 mos. post-RT. Data on potential confounding factors were collected prospectively, e.g. chemotherapy/tamoxifen exposure, smoking habits. Results: Among the first 50 pat. no case of RP-G2 and 3 cases of RP-G1 were diagnosed. No detectable VC-decline was found. The mean dose of the contoured CT sub-volumes with radiological changes was 39 Gy (range: 31–53). Conclusions: This preliminary analysis suggests that a V20 of < 30% is a safe dose volume level in postop RT for BC to avoid clinically significant RP and detectable VC-decline. Chest-CT could still detect RT-induced radiological changes in lung sub-volumes that received average doses in excess of 30 Gy. No significant financial relationships to disclose.
mTORC1 Inactivation Prevents and Eradicates Acute Lymphoblastic T-Cell Leukemia
Authors: Takayuki Hoshii, Atsuo Kasada, Tomoki Hatakeyama, Masashi Ohtani, Yuko Tadokoro, Kazuhito Naka, Tsuneo Ikenoue, Tomokatsu Ikawa, Hiroshi Kawamoto, Kimi Araki, Ken-ichi Yamamura, Atsushi Iwama, Satoshi Matsuda, Atsushi Hirao
Journal: Blood (2013)