tbuckley/cabot-search huggingface dataset:
STAT3 Establishes an Immunosuppressive Microenvironment during the Early Stages of Breast Carcinogenesis to Promote Tumor Growth and Metastasis
Authors: Laura M. Jones, Miranda L. Broz, Jill J. Ranger, John Ozcelik, Ryuhjin Ahn, Dongmei Zuo, Josie Ursini-Siegel, Michael T. Hallett, Matthew Krummel, William J. Muller
Journal: Cancer Research (2016)

Immunosurveillance constitutes the first step of cancer immunoediting in which developing malignant lesions are eliminated by antitumorigenic immune cells. However, the mechanisms by which neoplastic cells induce an immunosuppressive state to evade the immune response are still unclear. The transcription factor STAT3 has been implicated in breast carcinogenesis and tumor immunosuppression in advanced disease, but its involvement in early disease development has not been established. Here, we genetically ablated Stat3 in the tumor epithelia of the inducible PyVmT mammary tumor model and found that Stat3-deficient mice recapitulated the three phases of immunoediting: elimination, equilibrium, and escape. Pathologic analyses revealed that Stat3-deficient mice initially formed hyperplastic and early adenoma-like lesions that later completely regressed, thereby preventing the emergence of mammary tumors in the majority of animals. Furthermore, tumor regression was correlated with massive immune infiltration into the Stat3-deficient lesions, leading to their elimination. In a minority of animals, focal, nonmetastatic Stat3-deficient mammary tumors escaped immune surveillance after a long latency or equilibrium period. Taken together, our findings suggest that tumor epithelial expression of Stat3 plays a critical role in promoting an immunosuppressive tumor microenvironment during breast tumor initiation and progression, and prompt further investigation of Stat3-inhibitory strategies that may reactivate the immunosurveillance program.
Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma.
Authors: G Gasparini, N Weidner, P Bevilacqua, S Maluta, P Dalla Palma, O Caffo, M Barbareschi, P Boracchi, E Marubini, F Pozza
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine the absolute and relative value of microvessel density (MVD), p53 and c-erbB-2 protein expression, peritumoral lymphatic vessel invasion (PLVI), and conventional prognosticators in predicting relapse-free (RFS) and overall survival (OS) rates in patients with node-negative breast carcinoma (NNBC). PATIENTS AND METHODS We monitored 254 consecutive patients with NNBC for a median of 62 months. Intratumoral MVD was measured after microvessels were immunostained using anti-CD31 antibody. p53 and c-erbB-2 protein and hormone receptors were also determined immunocytochemically. Results were analyzed by both univariate and multivariate statistical analysis. RESULTS Univariate analysis showed that MVD was significantly predictive of both RFS (odds ratio [OR], 8.30; P = .0001) and OS (OR, 4.50; P = .012) when tested as a continuous or dichotomous variable. Likewise, tumor size (OR, 3.16; P = .0012), PLVI (OR, 4.36; P = .0009), estrogen receptor (ER) status (OR, 2.35; P = .016), progesterone receptor (PR) status (OR, 2.00; P = .017), and expression of p53 protein (OR, 2.82; P = .004) were significantly associated with RFS. Tumor size (OR, 3.80; P = .0038) and expression of p53 protein (OR, 2.58; P = .024) were significantly associated with OS by univariate analysis. Multivariate analysis showed that MVD (P = .0004), p53 protein expression (P = .0063), tumor size (P = .0144), and PLVI (P = .0033) were all significant and independent prognostic factors for RFS. However, only tumor size (P = .004) and MVD (P = .047) were independent predictors for OS. c-erbB2 expression was not associated with outcome by either univariate or multivariate analysis. CONCLUSION MVD, p53 expression, PLVI, and tumor size are independent prognostic indicators of recurrence, which are useful in selection of high-risk NNBC patients who may be eligible to receive adjuvant therapies.
The effect of androgen deprivation on mini-mental status examination in patients with biochemical recurrence of prostate cancer
Authors: W. Tan, M. Wehle, N. Graff-Radfford, S. Buskirk
Journal: Journal of Clinical Oncology (2007)

15592 Background: Androgen deprivation (AD) is a common treatment option for asymptomatic patients with biochemical recurrence of prostate cancer. Side effects such as sexual dysfunction, hot flashes, fatigue and gynecosmastia have been well documented. However, some of the side effects such as osteoporosis, insulin resistance, hyperglycemia, and anemia have only been recently recognized. The effects of AD on memory are not known. Aim: To determine if there is a decline in cognitive function(CF) in patients on AD using the modified MiniMental Status examination (MMSE). This test was chosen because it was simple, easy to administer and reproducible. Methods: We prospectively enrolled men with biochemical recurrence of prostate cancer prior to initiation of AD and monitored their MMSE at baseline, 2 ,and 4 months and while on AD (Mayo Clinic Jacksonville 8/2004- 9/2006). Results: 38 men were enrolled,however, only 20 men had at least 3 MMSE testing done. (5 withdrew consent, 13 had missing MMSE or lost to followup). The mean age was 68 years, mean baseline MMSE score was 27 and none had a clinical diagnosis of dementia or depression. Comparing the first MMSE and the 2nd MMSE score 19/20 patients had no decline of CF except for one patient who had a transient decline of 5 points in his MMSE score during a period of depression ,however, he had subsequent recovery of his score back to his normal baseline 27. Comparing the first and third MMSE score 20/20 patients had no decline of CF. The mean score change in MMSE score was -1 in 3 patients, 0 in 9 patients, +1 in 4 patients, +2 in 2 patients and +3 in 2 patients. There was no decline of 3 or more points in the mean score in any patient. Interestingly, 2 patients had an 3 point improvement of their MMSE score. We felt that it was secondary to being more familiar to the test process and not due to AD. Conclusions: There is no significant decline in MMSE score in men on AD at 2 and 4 months. MMSE might not be able to detect subtle changes in memory therefore, further study with more sensitive test to discriminate CF decline would be warranted and with longer followup cognitive impairement may be more evident. No significant financial relationships to disclose.
A phase I and pharmacologic study of belotecan in combination with cisplatin in patients with previously untreated extensive-stage disease small cell lung cancer
Authors: J. Lee, D. Lee, K. Bae, S. Kim, C. Suh, J. Shin, J. Hong, Y. Kang
Journal: Journal of Clinical Oncology (2007)

18053 Background: Belotecan (CKD602) is a novel camptothecin derivative antitumor agent. This phase I study was designed to determine the maximum-tolerated dose (MTD), toxicity profile, and dose-limiting toxicity (DLT) of belotecan in combination with cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer (ED SCLC). Furthermore, pharmacokinetics (PK) and preliminary antitumor activity of belotecan against SCLC were evaluated. Methods: Patients with ED SCLC, age 18–70, ECOG PS 0–2, no prior chemotherapy and adequate organ function were eligible. Cisplatin with fixed dose of 60 mg/m 2 was administered intravenously (i.v.) over 2 hours on day 1. Belotecan was administered iv as intermittent 30-minute infusions on days 1 to 4, starting dose of 0.40 mg/m 2 /day with increment of 0.05 mg/m 2 /day. Modified Fibonacci escalation was used (3 to 6 patients per cohort) and intra-patient dose escalation was not allowed. PK of belotecan was determined during the first treatment using non-compartmental pharmacokinetic analysis. Results: Seventeen patients were treated at 4 dose levels (0.40 to 0.55 mg/m 2 /day). At 0.55 mg/m 2 /day of belotecan, the DLT of grade 4 neutropenia with fever occurred in 2 of 5 patients, and therefore the MTD was 0.50 mg/m 2 /day. Interestingly, out of 17 patients, there were 14 partial responses (82.4%; 95% CI, 63.4% to 100.0%). PK analysis revealed that at 0.50 mg/m 2 /day, plasma clearance of belotecan was 5.78 ± 1.32 L/hr and terminal half-life was 8.55 ± 2.12 hr. Fraction of excreted amount in urine was 37.36 ± 5.55 %. PK of belotecan were not altered by administration of cisplatin, as compared with historical control. Conclusions: The MTD of belotecan was 0.50 mg/m 2 /day for intermittent 30-min i.v. infusion for 4 days in combination with cisplatin 60 mg/m 2 on day 1 every 3 weeks. Furthermore, very promising antitumor activity against SCLC was observed. The phase II study is being conducted now. No significant financial relationships to disclose.
Practical Bacteriology, Microbiology and Serum Therapy (Medical and Veterinary).
Journal: JAMA (1913)

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Abstract 11453: Cardiac Adipose-derived Stem Cells Exhibit High Therapeutic Effect on Cardiac Functional Recovery Following Myocardial Infraction
Authors: Hiroki Nagata, Masaaki, Masaya Miyagawa, Eiko Kohbayashi, Motohiro Arai, Masaaki Hoshiga, Toshiaki Hoshiga, Michio Asahi
Journal: Circulation (2012)

Background: Adipose-derived stem cells (AdSCs) have recently been shown to differentiate into cardiovascular lineage cells. However, little is known about the tissue origin-dependent difference of ...
A study of tolerance to treatment among the most frequent cancer in the elderly
Authors: N. G. Pilnik, R. Werbin, J. Dirienzo
Journal: Journal of Clinical Oncology (2006)

18609 Background: Besides, aging may influence pharmacological aspects due to functional reserve deterioration and comorbidities, affecting tolerance to treatment and increasing the likelihood of complications. Methods: 166 cancer pts (56 lung, 64 breast, and 46 colon), mean age 72 yrs, treated with Ch/Rt were studied. Lung cancer pts had PS 0:1 (2%); PS 1:17 (30%); and PS2:38 (68%). Breast cancer pts had PS 0:6 (9%); PS 1:25 (39%); PS 2:33 (52%). Colon cancer pts had PS 0:6 (13%); PS 1:17 (37%); PS 2:23 (50%). Comorbidities were hypertension, diabetes, arrhythmia, EPOC, coronary and gastrointestinal disease. All of the pts had adequate cardiac, hepatic, renal and bone marrow functions. Allergy, cardiovascular, gastrointestinal, hepatic, neurological, haematological and renal toxicities, and infection were evaluated following the WHO criteria. Toxicities were studied according to age and comorbidities, and correlated with the use of other medicines. QoL was studied through the improvement of symptoms and PS evolution. The Chi Square test was used for statistical analyses. Results: The prevalence of common toxicities in the lung cancer pts were anemia, 39 pts (70%), infection, 37 pts (66%), leukopenia 33 pts (59%), gastrointestinal 28 pts (50%). The most common toxicities in breast cancer, were leukopenia 43 pts (67%), gastrointestinal 37 pts (58%), infection 36 pts (56%), and anemia 32 pts (50%), while in colon cancer pts the toxicities found were gastrointestinal 38 pts (83%), anemia 33 pts (72%), leukopenia 32 pts (70%), and infection 25 pts (54%). There was no correlation between age and the most frequent toxicities. Grade 2 was the most common level of toxicity reached in all types of cancer studied. There was improvement in QoL when symptoms evolution and PS were evaluated independently of cancer type, 81% (134 pts) for symptoms (p &lt; 0.0001), and 72% (120 pts) for PS (p &lt; 0.0001) respectively. There was no association between age and toxicity grade, irrespective of toxicity type, age and comorbidities. Conclusions: Older pts in good general condition and with controlled morbidities may receive Ch/Rt if this treatment modality results in improvement of their QoL.-Low toxicities occurred in most of these pts, probably due to the fact that pts were adequately selected. No significant financial relationships to disclose.
Fluticasone propionate inhaled 3 hours after an early allergic reaction partially inhibits the late phase reaction
Authors: Bart Jacobs, Gail Gauvreau, Rick Watson, Abbey Torek, Karen Howie, Kieran Killian, Paul O'Byrne
Journal: European Respiratory Journal (2011)

Introduction:  Inhalation of 800μg budesonide (AJRCCM 1994;149:1447) or 500μg beclomethasone (JACI 1993;91:1163) upon resolution of the allergen-induced early phase response inhibits the late phase asthmatic response (LAR) by 39% and 70%, respectively. This has never been tested for the highly lipophilic corticosteroid fluticasone propionate (FP).   Methods:  This randomized double-blinded, placebo-controlled, 3-way crossover study (NCT00716963) was conducted in 6, mild allergic asthmatic patients with a documented dual bronchoconstrictor responses to inhaled allergen. Patients underwent 3 allergen challenges separated by 14 day washout periods. Patients inhaled placebo, 250μg or 1000μg FP at 3 h after allergen challenge, and the magnitude of the LAR was measured at regular intervals until 7 h post challenge. Sputum induction was performed before, 7 h and 24 h post challenge, and methacholine PC20 measured before and 24 h post challenge.   Results:  Five patients completed the study. 250μg and 1000μg FP significantly attenuated the LAR compared to placebo; the mean (SD) maximum% fall in FEV1 during the late response was 25.2% (6.2) with placebo, 15.1% (7.1) with 250μg FP (p=0.01), and 18.3% (8.2) with 1000μg FP (p=0.04). Inhibition of the LAR was 40% and 27% for 250μg and 1000μg FP, respectively. There was no effect of FP on allergen-induced sputum eosinophils, with a trend for reduced AHR which was not statistically significant.   Conclusions:  FP given three hours after allergen challenge attenuates the LAR, demonstrating that this lipophilic corticosteroid reduces the LAR when administered after allergen exposure.  This research was conducted with support from AstraZeneca.
Equipoise principle and NCI-sponsored clinical trials: Are investigators truly uncertain about their comparisons?
Authors: H. P. Soares, A. Kumar, F. Serdarevic, J. Fiorica, R. J. Wells, S. Swann, J. Buckner, D. Sargent, I. Hozo, B. Djulbegovic
Journal: Journal of Clinical Oncology (2005)

6050 Background: Studies in which the control intervention is believed to be inferior violate ethical and scientific principle of equipoise, may result in biased results findings, and could ultimately harm research subjects. Placebo or no-therapy controlled trials are particularly susceptible to this bias. We aimed to determine if equipoise principle was violated in National Cancer Institute (NCI) sponsored randomized clinical trials (RCT). We hypothesized that if the outcomes consistently and predictably favored active interventions over placebo/no-therapy, this would indicate a systematic bias in the choice of control intervention. Methods: All published and unpublished RCTs that were completed to date by six NCI cooperative groups were analyzed. Outcomes were analyzed from all trials that included placebo or no therapy arm as control versus any experimental intervention(s). A meta-analysis was performed to assess the effects of treatments on survival, event-free survival and treatment-related mortality. In addition, the investigators judgments about the relative value of active interventions versus placebo/no-therapy were deduced. Results: Data from 94 comparisons (84 RCTs), enrolling more than 16000 patients, were synthesized. No difference in survival was seen between experimental treatments and placebo/no therapy interventions [hazard ratio (HR): 0.99 (95%CI 0.94–1.03), p=0.5]. On the other hand, event-free survival slightly favored experimental treatments [HR: 0.87 (95%CI 0.83–0.91), p<0.00001]. Treatment-related mortality was worse in the experimental groups, [HR: 1.56 (95%CI 0.99–2.47), p=0.06]. In 52% of comparisons the placebo/no therapy arm was classified as superior by the trials’ investigators (p=0.677). Conclusions: The finding that placebo/no-therapy has equal chance to result in the outcomes similar to active interventions indicates that the NCI investigators were truly uncertain (i.e. equipoise) when they designed their studies. Hence, we concluded that there is no evidence of violation of equipoise in this set of publicly sponsored RCTs. This is in contrast to violation of equipoise described in the industry sponsored studies (Lancet 2000; 350:635). No significant financial relationships to disclose.
Changes in Clonal Expression During the Course of Acute Leukemia: Possible Subsets in Childhood Leukemia&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: H W Hann, P C Nowell, P Koch, J Minowada, J E Leitmeyer, C S August
Journal: JNCI Journal of the National Cancer Institute (1982)

We studied cell surface markers and chromosomes in the leukemia cells of a boy with the initial diagnosis of acute lymphocytic leukemia during 18 months from diagnosis to demise. During this time he received induction therapy, underwent bone marrow transplantation, and relapsed. The leukemia cells expressed three membrane phenotypes during different stages of disease: T-cell at diagnosis; T-cell, B-cell, and monocyte during the induction period; T-cell in the first relapse after bone marrow transplantation; and T-cell and B-cell during the terminal stage. Some cells expressed markers of two cell types, indicating a common origin of these cells. Cytogenetic studies during post-transplantation relapse showed abnormal marker chromosomes that indicated two major sublines. However, there was enough sharing of other aberrant chromosomes to suggest that these two populations presented sublines within the same neoplastic clone. We suggest that these leukemia cells were derived from a pluripotential cell prior to differentiation into cells of the lymphoid and monocytic series. This particular case may represent a subset of acute leukemia and may account for the resistance to conventional therapy.
Smoking induced satellite associations in a rural population of south India
Authors: Ranganadin Pajanivel, Uma Natarajan
Journal: European Respiratory Journal (2011)

A smoker is exposed to a variety of carcinogenic constituents present in cigarettes, making it necessary to analyze the cells at metaphase as these can be a health hazard to the future generations1. Cytogenetic assay in peripheral blood lymphocytes was done to assess the incidence of Satellite Associations among 30 smokers and 30 non-smokers in a rural population of South India. Smokers were divided into three groups based on their Smoking Index (SI): I - SI less than 150, II - SI 150 to 300, III - SI more than 300. An equal number of matched control individuals were selected and Lymphocyte cultures were set up from heparinised blood. The mean frequency of satellite association in smokers belonging to group I, II and III were 45 (44.25±3.30), 53 (53±3.46) and 67 (67±6.22) respectively, whereas the mean frequency of satellite association in non smokers was 29.83% (29.83±1.00). The frequency of Satellite Associations in smokers I, II and III increased with the increase in the frequency of their smoking index than their non smoking counterpart. The students' “t” test (“SSP” software) for satellite association was found to be highly significant at p<0.01 in all the three Smoker Group viz. I, II and III.These findings confirm the genotoxic effect of cigarette smoke on the chromosomes and can be used as a Smoking Cessation Intervention tool.

References: 

*   1. Falk HL. Chemical agents in cigarette smoke, In: Handbook of Physiology: Reaction to Environmental Agents, DHK Lee (Ed.). Baltimore, MD: Waverly, 1977, pp 199-211.
Tumor Grading by Implantation in Embryos. II. Grading of Some Human Astrocytomas2
Authors: G. V. Sherbet, M. S. Lakshmi
Journal: JNCI Journal of the National Cancer Institute (1974)

Six human astrocytomas were graded by a system based on assessment ot cellular responses of 16to 18-hour chick embryos to implanted tumors. Such grading of astrocytomas did not correlate with the grading system of Kernohan et al. Whereas the Kernohan grad ing of the astrocytomas did not correlate with the survival times of the patients, grading in embryos showed a positive correlation. The survival times decreased with increase of the product of grade in embryo × age of the patient. This grading system may allow prognostic assessments of individual cases.
Quality of care in non-small cell lung cancer (NSCLC): Findings from the Florida Initiative for Quality Cancer Care (FIQCC).
Authors: T. Tanvetyanon, M. Corman, W. J. Fulp, J. Lee, P. B. Jacobsen
Journal: Journal of Clinical Oncology (2010)

6018 Background: To date, no quality of care indicators (QI) specific for NSCLC are widely accepted. We proposed a set of QI and are reporting on quality of care using data from FIQCC consortium which is comprised of 11 oncology practices. In addition, this study explored the impact of patient volume on quality of care. Methods: Major care guidelines (NCCN, ACCP, ESMO, Ontario CC, ELCWP) were systematically reviewed for potential QI. Survey was conducted among NCCN NSCLC panel in 2008 for QI with strong agreement ratings. Chart abstraction manual was created, structured chart abstraction conducted for all NSCLC patients first seen by oncologist in 2006 in each site, and independent audits performed to ensure accuracy and reliability. Results: 10 NSCLC-specific QI were established. 531 charts were sampled from 11 sites: 4 sites classified as higher volume (median 2006 NSCLC-patient volume = 314; range 244-862) and 7 as lower volume (median = 129; range 90-217). Patient median age was 68 years; 14% stage-I, 6% stage-II, 26% stage-III, and 49% stage-IV/wet IIIB. Performance rates across practices for the QI ranged from 44-91% (Table). Among the lowest rates were 1) practice of brain staging before chemoradiation in stage-III, 2) formal assessment of unresectability in unresected early NSCLC, and 3) performance status assessment in advanced NSCLC. Conclusions: Areas with the greatest potential for improvement in the quality of care for NSCLC were related to nonchemotherapeutic interventions. We found limited evidence for the difference in quality of care based on patient volume. QI Practice rates % (N) Rates in higher-volume/lower-volume sites p values ≥2 N2 stations assessed at surgery 75 (99) 79/90 0.36 Post-op CT scan done by 6 months 64 (106) 68/59 0.41 Adjuvant chemo referral by 8 weeks 89 (54) 86/92 0.67 No adjuvant radiation in stage I, II 91 (70) 91/92 1.00 Unresected early stages, had surgical evaluation 60 (83) 67/56 0.37 Concurrent chemoRT for unresected stage III 90 (102) 91/89 0.75 Brain staging before chemoRT 59 (88) 63/56 0.67 Use standard chemo, early stages 79 (150) 84/75 0.22 Performance status assessed, advanced stages 44 (260) 54/32 < 0.001 Use standard chemo, advanced stages 84 (194) 79/90 0.07 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer