tbuckley/cabot-search huggingface dataset:
The effect of Cockcroft-Gault (CG) measurement of GFR on carboplatin dosage in ovarian cancer patients compared with Cr<sup>51</sup>-EDTA.
Authors: M. Okera, J. Peacock, A. Hobinchetti, A. Montes
Journal: Journal of Clinical Oncology (2011)

e15538 Background: The accepted gold standard for carboplatin dose calculation is the Calvert formula: Dose = (GFR + 25) x AUC. GFR (glomerular filtration rate) calculation is commonly made with formulae such as CG, which are based on serum creatinine. Cr51-EDTA, a radionuclide scan, also can be used to calculate GFR and is more accurate with closest estimation to inulin clearance (gold standard for GFR). The impact of factors such as body mass index (BMI), muscle mass and serum albumin upon the accuracy of CG versus EDTA is not well-defined. Many international clinical trials correct the AUC to a higher level when CG formula is applied. Methods: Identification of patients from local gynaecology-oncology database undergoing carboplatin-based chemotherapy for ovarian cancer, all of whom had Cr51-EDTA between January 2008 and January 2011. Evaluation of BMI, serum albumin, serum creatinine and disease status prior to chemotherapy. Comparison of theoretical Carboplatin doses based on Cr51-EDTA versus CG formula, termed Dose-EDTA and Dose-CG respectively. Results: 58 patients,mean age 61 years (range 31-81), mean BMI 27.8 (17.95-48.01). Mean albumin 40g/L (25-50) and mean serum creatinine 66umol/L (35-139). Carboplatin dose-CG exactly matched Dose-EDTA in only 1 patient (1.7%) and over-estimated carboplatin dose in 49 patients (84.5%), with over-estimation by ≥10% in 63.7% and ≥30% in 32.7%. Dose-CG underestimated carboplatin dose in 13.8%, with underestimation by ≥10% in 5.2%. Bland-Altman analysis showed that over-estimation of Dose-CG increased as the average dose increased. Multifactorial analysis is underway to identify patients at higher risk of over-estimated Dose-CG and will be presented at meeting. Conclusions: Carboplatin dosing based on CG measurement is frequently inaccurate and significantly overestimates the dose compared to Cr51-EDTA. The practice of increasing the AUC by one level when using CG will lead to significant overdosage of carboplatin in most ovarian cancer patients and should not be applied. Where facilities are available, consideration should be given to routine use of Cr51-EDTA to calculate carboplatin dosage.
Author reply to: 'Clinical thresholds for ambulatory blood pressure measurement reinvented?'
Authors: G Head, S Mihailidou, K Duggan, LJ Beilin, N Berry, MA Brown, AJ Bune, D Cowley, JP Chalmers, Prc Howe, J Hodgson, J Ludbrook, A Mangoni, B McGrath, Nelson, JE Sharman, M Stowasser
Journal: BMJ (2010)

Background: Twenty-four hour ambulatory blood pressure thresholds have been defined for the diagnosis of mild hypertension but not for its treatment or for other blood pressure thresholds used in the diagnosis of moderate to severe hypertension. We aimed to derive age and sex related ambulatory blood pressure equivalents to clinic blood pressure thresholds for diagnosis and treatment of hypertension. Methods: We collated 24 hour ambulatory blood pressure data, recorded with validated devices, from 11 centres across six Australian states (n=8575). We used least product regression to assess the relation between these measurements and clinic blood pressure measured by trained staff and in a smaller cohort by doctors (n=1693). Results: Mean age of participants was 56 years (SD 15) with mean body mass index 28.9 (5.5) and mean clinic systolic/diastolic blood pressure 142/82 mm Hg (19/12); 4626 (54%) were women. Average clinic measurements by trained staff were 6/3 mm Hg higher than daytime ambulatory blood pressure and 10/5 mm Hg higher than 24 hour blood pressure, but 9/7 mm Hg lower than clinic values measured by doctors. Daytime ambulatory equivalents derived from trained staff clinic measurements were 4/3 mm Hg less than the 140/90 mm Hg clinic threshold (lower limit of grade 1 hyperten sion), 2/2 mm Hg less than the 130/80 mm Hg threshold (target upper limit for patients with associated conditions), and 1/1 mm Hg less than the 125/75 mm Hg threshold. Equivalents were 1/2 mm Hg lower for women and 3/1 mm Hg lower in older people compared with the combined group. Conclusions: Our study provides daytime ambulatory blood pressure thresholds that are slightly lower than equivalent clinic values. Clinic blood pressure measurements taken by doctors were considerably higher than those taken by trained staff and therefore gave inappropriate estimates of ambulatory thresholds. These results provide a framework for the diagnosis and management of hypertension using ambulatory blood pressure values.
Effect of Tuftsin on In Vivo Development of 3-Methylcholanthrene-Induced Primary Fibrosarcoma and Lewis Lung Carcinoma in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R A Banks, K Nishioka, F Kazazi, G F Babcock
Journal: JNCI Journal of the National Cancer Institute (1985)

The effect of tuftsin therapy on tumor development was examined in a murine primary fibrosarcoma and the Lewis lung carcinoma systems. Following im injection of 3-methylcholanthrene (CAS: 56-49-5) on day 0, C57BL/10ScSn mice were treated weekly with 3 ip tuftsin injections beginning on day 1 or day 60. Similar patterns of tumor development were observed regardless of whether tuftsin therapy was immediate or delayed. Only modest differences in experimental and control tumor incidences were found upon termination of studies; however, treated animals developed significantly fewer tumors than controls early during the observation periods. Thus mean tumor latent periods varied significantly when therapy began on day 1 (103.6 days in controls vs. 119.1 in treated mice; P = .02) or 2 months later (104.6 days in controls vs. 115.3 in treated mice; P = .01). One day subsequent to intra-footpad implantation of 10(5) Lewis lung carcinoma cells, C57BL/6 mice received at least 10 iv injections of tuftsin and were compared with controls for variations in survival or lung tumor development. The mean survival time in treated mice, 41.2 days, differed sharply from that (30.1 days) in controls (P = .00001). Similar groups of mice varied significantly in mean metastatic lung colony counts when examined on day 30; there were 15.1 colonies in controls and 8.0 in experimental animals (P = .03).
Breast cancer in the Kingdom of Saudi Arabia: A review of all female breast cancer cases from the Saudi Cancer Registry (SCR) from 1994-2004.
Authors: A. D. Al Sayed, M. Shoukri, H. Al-Eid, T. Al-Tweigeri, A. Al-Dalee, M. Al-Shabanah, O. Al-Malik, A. A. Ezzat, D. S. Ajarim, S. Bazarbashi
Journal: Journal of Clinical Oncology (2010)

e12042 Background: Saudi Arabia (SA) is divided into 13 administrative regions (AR) and the first case registered in the Saudi Cancer Registry (SCR) was in 1994. The SCR through 5 regional offices collects all cancer cases using the World Heath Classification and the SEER staging system as the main reference for the data collected. Breast cancer in the most common malignancy in SA and is analyzed in details using the SCR database. Methods: All female breast cancer (FBC)cases in the SCR between 1994-2004 were reviewed for incidence age, pathology and stage regional difference and changing trends in various study variables were analyzed. Chi square and Fisher's exact tests were used for comparative analysis. Results: 6,529 cases of FBC over 10 years period from SCR were included. The median age was around 46 years. The number of cases have doubled from 450 in 1994 to 900 in 2004. Age standardized incidence rate ASR ranged from 12.6 to 15.4/100,000. Only 1.4 % had pure in situ disease at diagnosis. There is a statistically significant increase in incidence in three AR namely Riyadh, Makkah and eastern province. More than 76% of cases were invasive ductal cancer, followed by carcinoma/adenocarcinomas with no further details 6.8 % lobular 4.4% and medullary cancer 1.55%. The majorities of invasive cancers are regional with or without nodal involvement 45%, 16% have metastatic disease and about 23% are confined to the breast and in 14% the stage was unknown. G2 was most common in 34% of cases. A small percentage had bilateral disease and the incidence of left and right breast cancer were almost even. The number of unknown variable have improved over time. Conclusions: The SCR is a valuable source of information for incidence of various cancer in SA. The incidence of breast cancer is low and occur at younger age. The majority present with locally advanced or metastatic disease. Trends have show a significant increase in the incidence in three admistrative regions of SA. Data completion lacks throughness but has improved with time as with any cancer registry. Information regarding survival, prevelance and cancer risk need to collected to guide decision making for managing breast cancer in SA. No significant financial relationships to disclose.
Type C Virus Expression in Lymphoma-Paralysis-Prone Wild Mice2
Authors: Murray B. Gardner, Vaclav Klement, Robert R. Rongey, Patricia McConahey, John D. Estes, Robert J. Huebner
Journal: JNCI Journal of the National Cancer Institute (1976)

Abstract Wild mice trapped near Lake Casitas (LC) in southern California showed a high prevalence of infectious type C virus in the liver, spleen, and thymus within the first few weeks of life. By young adulthood about 80% of LC mice (including their genital tissues) were infected. Virus isolates from these mice cause lymphoma and lower limb paralysis under both natural and experimental conditions. Mice destined to develop paralysis showed higher levels of serum gs antigen early in life, whereas mice destined to develop lymphoma or remain free of these diseases could not be distinguished by this test. The individual variation in virus expression suggested that differences in virus type or in the immune or other host defense mechanisms greatly influenced susceptibility or resistance to indigenous type C virus-caused disease in LC wild mice.
Cilengitide in asymptomatic metastatic androgen independent prostate cancer (AIPC) patients (pts): A randomized phase II trial
Authors: D. A. Bradley, S. Daignault, C. Ryan, R. P. DiPaola, D. C. Smith, P. Mathew, M. Gross, A. P. Chen, E. T. Keller, M. H. Hussain
Journal: Journal of Clinical Oncology (2008)

5144 Background: Integrins αvβ3 and αvβ5 are involved in PC metastasis by regulating cell adhesion, migration, invasion, motility and angiogenesis. αvβ3 integrin is important in bone metabolism and may play a role in PC growth in bone. Cilengitide is a selective, competitive inhibitor of αvβ3 and αvβ5 integrins. Methods: Chemo-naïve pts with asymptomatic progressive metastatic AIPCa were randomized to cilengitide 500 mg or 2,000 mg IV 2X/week (wk) in 6-wk cycles using Simon 2-stage optimal design. Disease was assessed q 12 wks. The primary end point was 6 month (m) objective progression rate (PgR) (excluding PSA). Historically a 75% PgR is expected. We hypothesized cilengitide would lower the 6 m PgR to 55%. > 6 pts/arm with no Pg were needed to move to 2nd stage. Pts with asymptomatic Pg at 1st assessment were permitted to receive 1 more cycle followed by reassessment. Secondary end points include safety, response rate, changes in circulating tumor cells (CTCs) and bone markers. Results: 44 pts were accrued to 1st stage. Arms were balanced at baseline except for younger age (median 68yrs vs 74yrs) and lower PSA (median 66ng/ml vs 141ng/ml) in the 2,000mg arm. Median number of cycles was 3/arm (500mg arm: 1–8; 2,000 mg arm: 1- 15). At 6 m, 3 pts (14%) on the 500mg arm and 6 pts (27%) on the 2,000mg arm had not progressed. Best objective response was stable disease (SD); 27% on the 500 mg arm, 36% on 2000mg arm. 50% of the 24 pts who had Pg at 1st assessment stayed on study for an additional cycle. There were 3 grade (G) 3 and no G4 toxicities. At 12 weeks, analysis of bone markers did not reveal significant biologic trends. At Pg, bone specific alkaline phosphatase and N-telopeptide increased in all pts, less so in pts on the 2000mg arm and in pts who obtained SD at 6m. CTCs increased over time in both arms. Conclusions: Cilengitide was well tolerated. The 2,000 mg arm had a modest but not clinically significant effect so 2nd stage was not pursued. Neither dose level decreased the 6 m PgR. Decreased level of bone markers correlated with a trend towards decreased PgR. The unique study design using a non-Pg endpoint, not acting on PSA changes, and confirming Pg after 1st assessment was feasible. Supported by CTEP, Prostate SPORE Grant P50 CA069568–09, PC051375, Merck KGaA, PC051382, Immunicon. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Johnson & Johnson Merck KGaA
Expression of STAT proteins and interferon receptors in benign and malignant melanocytic lesions: Correlation with recurrence
Authors: R. C. Deconti, J. Messina, M. Decker, R. Welsh, L. Mora, R. Jove, A. Daud
Journal: Journal of Clinical Oncology (2004)

7514 Introduction: While the mechanism of action of Interferon α-2b (IFNα) in melanoma is not clear, IFNα receptors are known to signal through the \(\underline{\mathrm{Ja}}\)nus \(\underline{\mathrm{K}}\)inase (JAK) - \(\underline{\mathrm{S}}\)ignal \(\underline{\mathrm{T}}\)ransducers and \(\underline{\mathrm{A}}\)ctivators of \(\underline{\mathrm{T}}\)ransduction (STAT) pathway in melanoma cell lines. STAT 3 has been implicated as a tumor promoter and STAT 1 as a growth suppressor in some preclinical studies. We examined the expression of STAT proteins and IFN receptors in human melanocytic neoplasms by immunohistochemistry Methods: Compound Nevi (6), dysplastic nevi (4), congenital nevi (2), primary melanoma (14) and melanoma metastatic to the (40) sentinel lymph node (SLN) were examined. All patients with SLN mets were treated with standard IFN. All specimens were evaluated for activated or phospho-Stat 1 (p-STAT-1), phospho-Stat 3 (p-STAT-3), and IFN receptor by immunohistochemistry. Staining was scored from 1–3 based on % of tumor cells staining and intensity of stained cells. The recurrence history of patients with SLN metastasis was determined using the Moffitt melanoma database. Results: Only 1/6 compound nevi, 0/4 dysplastic nevi and 0/2 congenital nevi expressed p-STAT-3 while 6/14 primary melanomas had p-STAT-3. A total of 28/40 SLN metastases had evaluable and stainable tumor. Of these 15/28 had high-level expression of p-STAT 3 but only 4/28 had activated p-STAT-1 expression. Most tumors (18/22) expressed IFN receptors. 12/28 patients have recurred to date. Patients who recurred were more likely to express high levels of activated STAT 3 (70% expressed 3+ p-STAT-3) than those who did not recur (30% expressed 3+ p-STAT-3). Conclusion: p-STAT-3 expression was infrequent in normal melanocytes or benign (8%) lesions but more frequent in cutaneous melanoma (42%) and SLN mets (53%) .IFN receptor was expressed in 81% of SLN melanoma mets. Increased p-Stat-3 and decreased p-STAT-1 were positively correlated with recurrence. IFN receptor expression was not correlated to recurrence in this small sample but all components of the IFN-JAK-STAT pathway are present in human melanoma No significant financial relationships to disclose.
Treatment of recurrent ovarian cancer: increasing options--"recurrent" results.
Authors: R F Ozols
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.6.2177 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9196128 Treatment of recurrent ovarian cancer: increasing options--"recurrent" results. R F OzolsxR F OzolsSearch for articles by this author https://doi.org/10.1200/JCO.1997.15.6.2177 First Page PDF © 1997 by American Society of Clinical Oncology
Mechanism of Action of BCG-Tumor Cell Vaccines in the Generation of Systemic Tumor Immunity. I. Synergism Between BCG and Line 10 Tumor Cells in the Induction of an Inflammatory Response&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: M E Key, M G Hanna
Journal: JNCI Journal of the National Cancer Institute (1981)

The intradermal injection of a vaccine composed of 107 X-irradiated, syngeneic hepatocarcinoma line 10 (L10) cells admixed with 108Mycobacterium bovis strain BCG into inbred Sewall Wright strain 2 guinea pigs induced a local acute and then chronic inflammatory response. Cellular analysis of enzymatically dispersed dermal vaccination sites and regional lymph nodes revealed quantitative differences between the cellular infiltrate induced by a mixed BCG-tumor cell vaccine and the inflammation induced by either 108 BCG alone or 107 tumor cells alone. Analysis of dermal sites from days 1 through 4 following vaccination showed that sites receiving the BCG-tumor cell vaccine contained twofold to fourfold more cells than did those induced by BCG alone and more than fourfold the number of cells induced by L10 cells alone. These results indicated that there was a synergistic interaction between BCG and L10 cells in the induction of an inflammatory response at the site of vaccination. Analysis of the superficial distal axillary lymph nodes draining the site of vaccination revealed a similar synergistic interaction between BCG and L10, such that lymph nodes draining vaccination sites had a greater total cellular content than that induced by either BCG or L10 cells administered separately. When two other tumors, also syngeneic to strain 2 guinea pigs, were tested for their ability to interact synergistically with BCG to elicit an inflammatory response, it was found that the antigenically distinct hepatocarcinoma line 1 tumor also shared this characteristic with L10, whereas the L2C B-cell leukemia did not.
P-081 Serum tumor markers as predictors of overall response rate and clinical benefit in patients with advanced esophagogastric adenocarcinoma (EGA) treated with chemotherapy
Authors: S.P. Cortez Castedo, M. Gion Cortes, F. Longo Munoz, R. Ferreiro Monteagudo, V. Pachon Olmos, M. Rodriguez Garrote, M. Alsina, J. Munoz del Toro, A. Cortes Salgado, P. Reguera Puertas, A. Madariaga Urrutia, M. Villamayor Delgado, O. Martinez Saez, J. Molina Cerrillo, M.E. Olmedo Garcia, E. Grande, C. Guillen-Ponce, A. Carrato
Journal: Annals of Oncology (2015)
Efficacy of vinorelbine plus trastuzumab (VT) in patients (pts) with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab (T).
Authors: V. Freixinós, G. Sánchez-Ollé, L. De Mattos-Arruda, S. Di Cosimo, C. Saura, P. Gomez, J. M. Perez-Garcia, J. Cortes, J. Baselga, M. Bellet
Journal: Journal of Clinical Oncology (2010)

1113 Background: VT has proven active in HER2+ MBC: Response rate (RR) and time to progression (TTP) in first- and second-line therapy: 51-84%, 7.5-17 months (m) and 51-66%, 3.5-9 m, respectively. However, all pts included in such studies were T-naive. In contrast, few data regarding the efficacy of VT in pts with prior T treatment (Tpt) has been reported and preclinical data do not support a synergism of V and T in T-resistant cell lines. Our aim was to describe the efficacy of VT in Tpt pts compared to a T-naive group and to study predictive factors of TTP in both groups. Methods: Medical reports of all pts receiving VT for MBC between 2001 and 2009 were selected. Those previously treated with T for MBC and/or relapsing ≤ 6 m after completion of adjuvant T constituted the Tpt group. Pts without previous exposure to T formed the T-naive subset. RR, clinical benefit rate (CBR), and TTP were analyzed. Baseline characteristics, along with time of prior T treatment in Tpt group, were analyzed as potential variables associated to TTP. Results: 26 Tpt and 20 T-naive pts were identified. No statistically significant differences were found in median (M) age (59 vs. 61), disease-free Interval ≥2 years (59% vs. 63%), prior chemotherapy (anthracyclines 77% vs. 80%, taxanes 81% vs. 55%, capecitabine 35% vs. 10%), visceral involvement (67% vs. 75%), measurable disease (85% vs. 60%), CNS involvement (31% vs. 10%) and ≤2 M1 sites (73% vs. 75%). Only a lower % of ER and PR negative (25% vs. 56%, p <0.05) was observed in TpT group. Among TpT pts, M number of prior chemo with T were 1 (0-2) and M weeks of prior T was 53 (6-225). VT represented the first, second, and ≥third line for MBC in 3, 7, and 16 pts in TpT and in 12, 3, and 5 pts in T-naive group, respectively. For efficacy data, see Table. There was a trend to better TTP in pts without CNS involvement (p=0.09). In a multivariate analysis, the only independent factor associated to TTP was T pretreatment, even controlling by number of prior chemo lines or CNS involvement. Conclusions: In our series, prior T exposure was associated with shorter TTP to VT combination. Nevertherless VT maintained meaningful activity (CBR 48, TTP 6.5 m) in T-pretreated subset. N RR (%) CBR (%) M TTP, m Tpt 26 27 48 6.5 T-naive 20 42 74 16.8 p - NS NS 0.02 No significant financial relationships to disclose.
Prognostic Significance of Angiogenesis and <i>Ki-67</i>, <i>p53</i>, and <i>p21</i> Expression: A Population-Based Endometrial Carcinoma Study
Authors: Helga B. Salvesen, Ole Erik Iversen, Lars A. Akslen
Journal: Journal of Clinical Oncology (1999)

PURPOSE: For endometrial carcinoma patients, there is a need for improved identification of high-risk groups that may benefit from postoperative adjuvant therapy. We therefore studied the prognostic impact of markers for cell proliferation, cell-cycle regulation, and angiogenesis among endometrial carcinoma patients in a population-based setting. PATIENTS AND METHODS: All patients diagnosed with endometrial carcinoma between 1981 and 1985 in Hordaland County, Norway, were studied. The median follow-up for the survivors was 11.5 years (range, 8 to 15 years), with no patient lost because of insufficient follow-up information. Paraffin-embedded tumor tissue, available in 96% of the cases (n = 142), was studied immunohistochemically for microvessel density (MVD) and expression of Ki-67, p53, and p21 proteins. We used the hot spot method for calculation of MVD, and expression of Ki-67 and p21 protein, because this approach may increase the probability of detecting small aggressive clones of possible prognostic relevance. The importance of these tumor markers was investigated in univariate survival analyses and Cox regression analysis. RESULTS: The majority of traditional clinicopathologic variables was significantly associated with the tumor biomarkers. Age, International Federation of Gynecology and Obstetrics (FIGO) stage, histologic type, histologic grade, MVD, as well as Ki-67, p53, and p21 protein expression, all significantly influenced survival in univariate analyses (P ≤ .05). In the Cox regression analysis, age, FIGO stage, MVD, Ki-67 expression, and p53 expression were the only variables with independent prognostic impact (P ≤ .05), whereas histologic type, histologic grade, and p21 expression had no independent influence. A group of high-risk patients with more than one unfavorable marker was identified. CONCLUSION: In addition to age and FIGO stage, MVD, Ki-67, and p53 protein expression showed an independent prognostic impact. Thus, information derived from routine histologic specimens identified a subgroup of high-risk endometrial carcinoma patients in this population-based study.