tbuckley/cabot-search huggingface dataset:
Irradiation and Prolactin Effects on Rat Mammary Carcinogenesis: Intrasplenic Pituitary and Estrone Capsule Implants&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K H Clifton, J Yasukawa-Barnes, M A Tanner, R V Haning
Journal: JNCI Journal of the National Cancer Institute (1985)

The implantation of silicone capsules that contained estrone and that were adjacent to grafts of anterior pituitary tissue in the spleens of adrenalectomized glucocorticoid-deficient inbred F344 rats resulted in high circulating prolactin (Prl) levels without the untoward effects of chronic hyperestrogenism or of grafts of Prl-secreting pituitary tumors. All peripheral serum estrone titers were below the titers in sera of proestrous untreated intact rats. Peripheral serum estrone and Prl levels were, however, a function of capsule surface area over the capsule sizes tested (12-74 mm2); the elevated Prl levels persisted for as long as 700 days. In adrenalectomized glucocorticoid-deficient female rats, both 5 Gy gamma-irradiation alone and intrasplenic pituitary-estrone implants alone induced mammary carcinomas; the combination of these treatments induced a greater incidence of first carcinomas and reduced first carcinoma latency. There were, however, no marked differences in tumor incidence or latency due to differences in estrone capsule size. Finally, ovariectomy reduced first carcinoma risk in irradiated, pituitary-estrone-implanted rats but did not change the time of maximum risk. Ovarian secretory activity thus persisted in such rats and ovarian hormones synergized with Prl in mammary carcinoma induction.
Predictive biomarkers for preoperative endocrine therapy of stage II-III breast cancer by tissue microarrays
Authors: M. Zoubir, M. Mathieu, C. Liedtke, F. Bidard, S. Delaloge, L. Corley, M. Spielmann, L. Pusztai, F. André, W. F. Symmans
Journal: Journal of Clinical Oncology (2008)

560 Background: The goal of this study was to identify predictive biomarkers for the efficacy of preoperative endocrine therapy (ET). Methods: We constructed a tissue microarray from 80 primary breast cancers (BC) obtained before the administration of preoperative ET (aromatase inhibitor [AI] N=48, or tamoxifen [TAM] N= 32). Immunostainings were performed for 12 different markers. ER, PR, phosphoSer118 ER, pMAPK, PAK1 were analyzed as continuous variables according to % of tumor cell stained and intensity of staining. P53, bcl2, HER2, IGFR1, pAKT, AIB1, MAP-Tau were analyzed as dichotomized variables (positive or negative). Treatment efficacy was defined as objective tumor response according to the RECIST criteria. Association between markers and response was assessed by t test for continuous and by chi-square test for dichotomized variables. Results: The median age was 79 years (67–100). Overall response rate was 55% (n=44), and it was 47% with tamoxifen and 60% with aromatase inhibitors (p=0.23). Immunostainings for p53, bcl2, HER2, IGFR1, pAKT, MAP-tau were positive in 13 (20%), 45 (74%), 4 (6%), 14 (21%), 13 (21%), 35 (56%) BC. Expression of p53, bcl2, HER2, pAKT, MAP-Tau, ER, PR, Pser118ER, PAK1, pMAPK were not associated with response to ET. However, the response rates were significantly higher in patients with IGFR1 expression (ORR= 79% for IGFR1+ versus 44% for IGFR1- tumors, p=0.02). We then assessed whether biomarkers could predict for efficacy of AI over TAM. AI were more effective compared to TAM in patients with MAP-Tau negative tumors (p=0.04). A nonsignificant trend for interaction was observed between MAP-Tau expression and treatment (AI versus TAM) efficacy (p=0.10). Conclusions: The present study suggests that preoperative endocrine therapy is highly effective in patients with IGFR1-positive tumors; and that MAP-tau, an ER-regulated gene, is a candidate biomarker to select patients between AI and TAM. These data require further validation due to multihypothesis testing and small sample size of the study. No significant financial relationships to disclose.
Utilization and impact of surgical technique on the performance of pelvic lymph node dissection at radical prostatectomy: Results from the SEARCH database.
Authors: Kathleen F. McGinley, Xizi Sun, Lauren E. Howard, William J. Aronson, Martha K. Terris, Christopher J. Kane, Christopher L. Amling, Matthew R. Cooperberg, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2015)

73 Background: Performance of a pelvic lymph node dissection (PLND) with radical prostatectomy (RP) is critical for staging and treatment of high-risk prostate cancer (PC). Conversely, performance of a PLND in low-risk PC contributes to morbidity with minimal benefit. Robot-assisted laparoscopic RP (RARP) is associated with decreased PLND use. We evaluated PLND use over time, stratified by PC risk group and surgical technique. Methods: We used SEARCH to identify men who had open RP (ORP) or RARP from 2006-2013 with complete data. Univariable logistic regression was used to test the association between age, race, BMI, number of positive cores, AUA risk group, year, center, and surgical technique on PLND use. Multivariable logistic analysis was used to examine surgical technique and PLND performance stratified by AUA risk-group. Spearman correlation was used to examine temporal changes in PLND utilization stratified by risk-group and surgical technique. Results: 1,439 men met inclusion criteria. Of these, 66% had a PLND. On univariable analysis, age, year, number of positive cores, AUA risk group, center, and surgical technique were significantly associated with PLND performance (all p&lt;0.02). On multivariable analysis, when adjusted for age, race, BMI, number of positive cores, year, and center, RARP was associated with a 89% decreased use of PLND in the low-risk group, 85% decreased in intermediate risk, and 86% decreased in high risk men (all p≤0.002). Over time, PLND was increasingly used with RARP in low-risk patients (p=0.022); a trend of increased PLND performance with RARP in high risk men was noted (p=0.077) reaching ~85% in 2012-2013 vs. ~95% in ORP. For ORP, PLND use did not significantly change over time except a trend of fewer PLND in low-risk men which decreased to ~35% (p=0.064) in 2012-2013. Conclusions: Regardless of risk group, PLND is markedly less likely to be performed when a RARP is done. While improved over time, PLND remains over-utilized in low-risk men and under-utilized in high risk men regardless of surgical technique.
Small-Lymphocyte Subpopulation Rich in Effector Cells Against Walker Carcinosarcoma 2562
Authors: Yoshihiro Kinoshita, Shuhei Kimura, Yoshio Komano, Megumu Koshikawa, Eiji Inamoto
Journal: JNCI Journal of the National Cancer Institute (1974)

A method to separate Walker carcinosarcoma 256 cells (WCSC) yielded a fraction of over 99% pure WCSC. The fraction, treated by freezing and thawing more than 3 times, was used to sensitize rats. Three small-lymphocyte subpopulations [lighter (LSL), intermed iate (ISL), and heavier (HSL)] were obtained from the lymph nodes of immunized rats by a combination of discontinuous density-gradient centrifugation and elution through a column of absorbent-cotton lumps. To estimate the subPQPulation with the highest concentration of effector cells, a mixed culture ot viable WCSC was introduced to each subpopulation. The HSL was rich in effector Iymphocytes, compared with the other subclasses. Prior treatment of the HSL with a heterologous antiserum (AHSLAS) prepared from an HSL subclass of thymus Iymphocytes markedly reduced cytotoxic activity of effector cells, whereas prior treatment with an antiserum (ALSLAS) prepared frem an LSL subclass of thymus Iymphocytes did not. This result suggested that surface-antigen characteristics of effector Iymphocytes corresponded with those of the cells of the HSL thymus subclass and that effector cells were derived from that subpopulation. Growth of transplantable tumor was remarkably enhanced by AHSLAS injections in rats, but was little enhanced by ALSLAS.
Late-breaking abstract: Pathological analysis of acute exacerbation of idiopathic pulmonary fibrosis (IPF)
Authors: Yuh Fukuda, Mika Terasaki, Mikiko Takahashi, Shinobu Kunugi, Yasuhiro Terasaki, Hirokazu Urushiyama, Arata Azuma
Journal: European Respiratory Journal (2011)

The patients with IPF show occasionally acute exacerbation in their clinical courses. However the details of pathology of acute exacerbation of IPF are not well investigated.   Patients and methods:  We studied clinico-pathologically 15 autopsy cases of acute exacerbation of IPF. The clinical symptoms of acute exacerbation were acute respiratory distress syndrome, but multiple organ failure (MOF) was not associated. The intervals of acute exacerbation and death were 3 days to 6 months. The triggers of acute exacerbation were the infection in 3 patients, myocardial infarction in 3 patients, surgical operation in 4 patients, chemotherapy for cancer in 1 patient and unknown in 7 patients. All patients were treated with steroid. Autopsied lung tissues were observed with light microscopy and immunohistochemistry.   Results:  The lungs of all cases showed pathologically some stage of diffuse alveolar damage (DAD) coincident with the period after acute exacerbation. In 11 cases, several stages of DAD were recognized in the lungs of same patient. DAD is found exclusively in the area without honeycombing. Though 5 cases showed also bud-type intra-alveolar fibrosis, which composed of accumulated myofibroblasts with few vessels and occasionally connected with ring-like DAD fibrosis. We do not interpret these findings as OP, but DAD. In addition to DAD, fibroblastic foci were frequently observed in 9 cases including the walls of honeycombing. The activity of IPF itself was estimated to be high in these patients.   Conclusion:  The pathological findings of acute exacerbation are DAD, and the several stages of DAD are characteristically observed in the same patient, which are similar to DAD caused by drug injury.
Resource and quality information provided by compliance with NCCN hereditary breast cancer guidelines.
Authors: Peter J. Levonian, Jeffrey Landercasper, Choua Vang, Kristen Marcou, Rima Al Hajj, Mohammed Al-Hamadani
Journal: Journal of Clinical Oncology (2013)

e17583 Background: NCCN provides guidelines for breast cancer genetic risk assessment and testing. Measuring compliance with NCCN Guidelines (NG) can identify quality gaps. Methods: After IRB approval, a retrospective review of a prospective database of breast cancer patients was conducted to measure compliance with NG for genetic counseling and BRCA testing. Entry criteria were breast cancer patients with diagnosis and treatment at our center, during the 3 year period ending 12/31/11. Genetic counselors (GC) used NG and BRCAPRO modeling in all patients. Surgeon and GC pedigree analyses were compared. A change to the history was significant if the GC identified information that led to increased or decreased cases of breast or ovarian ca. Results: Surgeons constructed pedigrees in 675 breast cancer patients and referred 42% (286/675) to the GC. The decision to refer was NCCN compliant in 671/675 (99%). The GC corrected the pedigree in 14% (39/286); nearly all due to the GC identifying extra breast or ovarian cancers. The mean BRCAPRO probability in referred patients was 7.2%. Fifty-nine percent (170/286) of patients seen by the GC received a recommendation for BRCA testing. The NG compliance rate for testing was 98% (170/174). Of 174 BRCA tests offered to patients, 74% (128/174) underwent testing. In tested patients, there were 4% BRCA1+, 5% BRCA 2+, and 1% uncertain variants. Total patient charges for 128 tests were $696,000 ($4000/test). If the threshold for testing was BRCAPRO &gt; 5% or &gt;10%, then 69 ($276,000) and 45($180,000) (p&lt;0.001) patient charges would have occurred, and no patient with BRCA + status would have been missed. Conclusions: High rates of NCCN guideline compliance for genetic counseling and testing are achievable. Our GC's improve accuracy of pedigree assessment and demonstrate adherence to NCCN guidelines, resulting in more testing compared to BRCAPRO modeling. The balance between different methods to trigger testing, their sensitivity, and cost deserves more study, but the observational data contained herein provides information for provider and payer stakeholders regarding estimated GC resources and cost of care.
Water Content and Proton Spin Relaxation Time for Neoplastic and Non-Neoplastic Tissues From Mice and Humans 2
Authors: W. R. Inch, J. A. McCredie, R. R. Knispel, R. T. Thompson, M. M. Pintar
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Water Content and Proton Spin Relaxation Time for Neoplastic and Non-Neoplastic Tissues From Mice and Humans Get access W. R. Inch, W. R. Inch Search for other works by this author on: Oxford Academic PubMed Google Scholar J. A. McCredie, J. A. McCredie Search for other works by this author on: Oxford Academic PubMed Google Scholar R. R. Knispel, R. R. Knispel Search for other works by this author on: Oxford Academic PubMed Google Scholar R. T. Thompson, R. T. Thompson Search for other works by this author on: Oxford Academic PubMed Google Scholar M. M. Pintar M. M. Pintar Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 2, February 1974, Pages 353–356, https://doi.org/10.1093/jnci/52.2.353 Published: 01 February 1974 Article history Received: 11 June 1973 Accepted: 28 September 1973 Published: 01 February 1974
A randomized, open-label CECOG phase II study evaluating the efficacy and safety of FOLFOX6 + cetuximab versus FOLFIRI + cetuximab as first-line therapy in patients (pts) with metastatic colorectal cancer (mCRC)
Authors: T. E. Ciuleanu, G. Kurteva, J. Ocvirk, S. Beslija, I. Koza, D. Papamichael, D. Vrbanec, T. Brodowicz, W. Scheithauer, C. C. Zielinski
Journal: Journal of Clinical Oncology (2008)

4032 Background: FOLFOX6 and FOLFIRI are standard first-line regimens in mCRC. The monoclonal antibody cetuximab is active in combination with both regimens. This trial evaluated cetuximab+FOLFOX6 (Arm A) and cetuximab+FOLFIRI (Arm B) as first-line therapy in mCRC. Methods: Patients (pts) were randomized to FOLFOX6 (folinic acid 400 mg/m2 given with oxaliplatin [OX] 100 mg/m2, followed by 5-FU 400 mg/m2 bolus, then 5-FU 2400 mg/m2 over 46 h) or FOLFIRI (same as FOLFOX-6 except irinotecan 180 mg/m2 instead of OX) every 2 wks. Both arms received cetuximab (400 mg/m2 initial dose then 250 mg/m2/wk). Primary endpoint: progression free survival (PFS) at 9 mo. Secondary endpoints: 3-, 6-, and 12-mo PFS, objective response rate (RR), overall survival (OS), and toxicity. Results: Between July 2005−July 2006, 155 pts (25 centers in 13 countries) were randomized to Arm A (n=77) or Arm B (n=78). In total, 151 pts (median age 62 yrs; 88 [58%] males) received study treatment (A: n=77, B: n=74). In all, 84 pts (56%) had an ECOG PS of 0 and 89/117 (76%) available samples had EGFR detected. Grade 3/4 adverse events occurring in ≥5% pts were neutropenia (29%/20% [A/B]), diarrhea (10%/14%), rash (7%/4%), dermatitis acneiform (5%/3%). PFS rates are in the table. Best overall confirmed RRs were 43% (A) and 45% (B). Disease control was achieved in 83% (A) and 77% (B). No relevant differences in response and PFS rates relating to EGFR status were observed. Current estimates of median OS based on 77 events are 17.4 mo (A) and 18.9 mo (B). Conclusions: Cetuximab, in combination with FOLFOX6 or FOLFIRI, is an active regimen in previously untreated mCRC. RRs and OS were similar and no significant difference in PFS was observed. With the exception of skin reactions, the safety profile of both regimens combined with cetuximab was similar to that of chemotherapy alone. PFS (%) Time (mo) Arm A (n=77) Arm B (n=74) Difference (95% CI) 3 92 78 13 (2; 25) 6 69 69 0 (-16; 16) 9 47 34 12 (-5; 29) 12 18 18 1 (-13; 14) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ebewe, Baxter, Merck Ebewe, Merck, Pfizer, sanofi-aventis, Pfizer Merck, Pfizer, sanofi-aventis
A new “gold standard” for assessment of prognosis (prog) understanding among advanced cancer patients (acp): Narrative interviews of patients in phase I trials and invested third party observers (itpo)
Authors: C. K. Daugherty, N. Stein, T. Trabasso, F. J. Hlubocky
Journal: Journal of Clinical Oncology (2004)

8134 Background: Despite terminal illness, prior research shows acp: overestimate survival, provide little acknowledgement (ack) of prog, and have curative care goals. Yet, this research may not accurately reflect prog awareness as it has not accounted for how fear, anxiety, and hope effect measured responses to queries about when (or if) acp believe they will die. This research has also not included valuable observational experiences of those who bear witness to acp illness experiences. Methods: Narrative analysis explains effects of emotion on cognitive understanding by seeking descriptions of prior experiences and assessing goal appraisal processes. We studied its use on qualitative interviews of acp and their itpo (spouses/significant others). Results: To date, 28 terminally ill, acp receiving experimental (phase I trial) chemotherapy and 28 itpo have been separately interviewed: 50% male; median age 57 (23–78); 90% married; 96% Caucasian; 57% >high school education; expected median prog: 8 months. Quantitative interview data include, 1.) Likert scores (1–10) of likelihood of chemotherapy in: “halting” cancer (mean 7.0, with higher scores among women acp), producing “remission” (mean 6.4), and (among 30% stating it possible) “curing” (mean 7.1); and, 2.) Scales of affective balance and positive ways of thinking with: itpo with more depressed mood (p<.008), and acp with greater changes in thinking about the value of their life (p<0.1). Narrative analysis reveals that within virtually all acp-itpo interview pairs, there was an ack of a terminal prog—although many did not describe physician disclosure of prog and many acks came outside specific queries about prog understanding. Conclusions: While—in response to structured queries—acp state both significant expectations of benefit from chemotherapy and inaccurate estimates of survival, narrative analyses of acp and itpo descriptions of illness experiences provide a more accurate portrayal of patient understanding of prog. No significant financial relationships to disclose.
<i>Notes from the Field</i>: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses — Brazil, 2015
Authors: Roosecelis Brasil Martines, Julu Bhatnagar, M. Kelly Keating, Luciana Silva-Flannery, Atis Muehlenbachs, Joy Gary, Cynthia Goldsmith, Gillian Hale, Jana Ritter, Dominique Rollin, Wun-Ju Shieh, Kleber G. Luz, Ana Maria de Oliveira Ramos, Helaine Pompeia Freire Davi, Wanderson Kleber de Oliveria, Robert Lanciotti, Amy Lambert, Sherif Zaki
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. Zika virus was first reported in Brazil in May 2015 (1). By February 9, 2016, local transmission of infection had been reported in 26 countries or territories in the Americas.* Infection is usually asymptomatic, and, when symptoms are present, typically results in mild and self-limited illness with symptoms including fever, rash, arthralgia, and conjunctivitis. However, a surge in the number of children born with microcephaly was noted in regions of Brazil with a high prevalence of suspected Zika virus disease cases. More than 4,700 suspected cases of microcephaly were reported from mid-2015 through January 2016, although additional investigations might eventually result in a revised lower number (2). In response, the Brazil Ministry of Health established a task force to further investigate possible connections between the virus and brain anomalies in infants (3).
Volumetric 3D CT analysis - an early predictor of response to therapy
Authors: L. H. Schwartz, S. Curran, R. Trocola, J. Randazzo, D. Ilson, D. Kelsen, M. Shah
Journal: Journal of Clinical Oncology (2007)

4576 Background: Evidence suggests that changes in unidimensional measurements (using RECIST criteria) may not accurately reflect actual changes in tumor size, and do not correlate well with other biomarkers of response, tumor progression, or patient outcome. We evaluated changes in tumor volume of target lesions with volumetric CT, and compared them with response assessments derived from RECIST criteria. Methods: We evaluated target lesions, including lymph node, liver, peritoneal and lung metastases in 25 patients with metastatic gastric cancer or gastroespohageal junction adenocarcinoma treated on a phase II clinical trial with irinotecan, cisplatin and bevacizumab. All patients underwent thin-section multidetector CT at baseline and 6-week follow-up for 10 cycles. Target lesions were measured unidimensionally and volumetrically, using validated automated and semiautomated segmentation algorithms. For initial analysis, correlation was made with the RECIST response using a cut-off value of 65% volume change. A ratio of change in RECIST measure to volume measure was calculated at time of maximal clinical response for each patient, as well as for responders versus non-responders. Results: 18 of 25 (72%) patients showed a clinical response. Of these 18 responders, 5, 6, 4, and 3 were identified as responders using RECIST criteria after cycles 1, 2, 3, and 4, respectively. Using a cut-off of 65% volume change, 14 of these responders were indentified after cycle 1, and 4 were identified after cycle 2. Using a cut-off value of 65%, volume measurements identified responders a mean of 50.3 days earlier than did RECIST criteria. There was a statistically significant (p&lt;0.01) change in ratio of volume measurement change to RECIST measurement change for responding versus stable patients. Conclusions: Volumetric change in tumor size appears to predict clinical response earlier than do RECIST criteria in the majority of cases. Changes in volume are more sensitive because they exhibit a wider dynamic range. Ratios of size changes volumetrically appears to better discriminate RECIST responders from those with stable disease. Further work is needed to define the biologically relevant cut-off value for volume change, and to correlate volume change with other biomarkers. No significant financial relationships to disclose.
TCT-287 The diastolic backwards-travelling decompression “suction” wave correlates with simultaneously acquired indices of diastolic function: corroboration of the origin of the suction wave
Authors: Andrew Ladwiniec, Paul A. White, Sukhjinder S. Nijjer, Michael O'Sullivan, Nick E. West, Justin E. Davies, Stephen P. Hoole
Journal: Journal of the American College of Cardiology (2015)