tbuckley/cabot-search huggingface dataset:
CD20-immunotargeting of malignant melanoma.
Authors: S. N. Wagner, R. Somasundaram, A. Pinc, P. A. Van Belle, C. Wagner, M. Hoermann, G. Karanikas, G. Stingl, D. Elder, M. Herlyn
Journal: Journal of Clinical Oncology (2010)

8565 Background: Melanomas, like other malignancies, contain distinct subpopulations of cells. These subpopulations provide the cellular basis for the complex biology of the disease including phenomena such as self-renewal, differentiation, and tumor initiation, maintenance and progression, and may have major translational impact. In melanoma, several subpopulations - some with stem cell-like characteristics - have been described including one expressing CD20. Methods: multispectral imaging; xenografting onto CB17 SCID and NOD/SCID/γc-/- mice; adjuvant treatment with rituximab in 9 stage IV (M1a-c) melanoma patients, of whom the majority had received multiple prior systemic therapies. Induction treatment at 375 mg/m2 qw for 4 wk followed by maintenance therapy at 375 mg/m2 every 8 wk. Treatment was stopped after 2 years or with development of progressive disease. Results: We show by multispectral imaging that CD20 can be expressed on melanoma cells in human tumor samples. Furthermore, western blot analysis revealed expression of CD20 in lysates from human melanoma xenografts after serial in vivo passaging, consistent with environmental induction. Growth of human melanoma xenografts in two different preclinical in vivo models was significantly reduced by systemic administration of a monoclonal anti-CD20 antibody. Based on these results, we initiated a small phase II pilot trial on adjuvant treatment with an anti-CD20 antibody in stage IV (M1a-c) melanoma patients. Treatment was well tolerated. After 2 years, 6 patients (66%) are still disease-free, the 2 years OS rate was 100%. 2 patients died thereafter (22%). With a mean DFI and OS of 27+ months anti-CD20 treated patients show a > 3-fold longer median DFI and a somewhat higher median OS as compared to data obtained from large prospective clinical trials and retrospective analyses of stage IV melanoma patient cohorts, that have been treated by complete metastasectomy. Conclusions: Though patient numbers included in the present clinical study are too small for definitive conclusions, immunotargeting of CD20 may represent a first example of the potential therapeutic value of targeting melanoma subpopulations. Application of these initial clinical observations in larger trials is under way. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
Circulating tumor cells (CTC) in small cell lung cancer (SCLC), a promising prognostic factor.
Authors: T. J. Hiltermann, J. Liesker, H. Schouwink, J. Kaajan, H. M. Boezen, H. Tissing, A. Tibbe, L. W. Terstappen, H. J. Groen
Journal: Journal of Clinical Oncology (2010)

7630 Background: Prognostic models for SCLC are using performance score (PS), laboratory tests or disease stage assessed by imaging tests. Even the recently introduced TNM system show that increasing from stage 1A (T1N0M0, 5 year survival 38%) to stage IV (metastasized, 5 year survival 1%) still provides us with a poor prognostic assessment. In this study we evaluated the use of CTC as a prognostic marker for Overall Survival (OS) in SCLC. Methods: In an ongoing study, patients (pts) with pathological proven SCLC were treated with firstline cisplatin /etoposide for a maximum of 4 cycles. Prior to the start, prior to the second cycle and at the end of chemotherapy 20 mL of whole blood was drawn and within 72 hours analyzed for circulating cells using CellTracks technology at a central laboratory (Veridex, Enschede, the Netherlands). Pts were staged as limited or extensive disease (IASLC 2009). Clinical data and CTC characteristics were analyzed in a blinded fashion. Pts were stratified into unfavorable and favorable prognostic groups based on CTC levels ≥ 2 or < 2 CTCs/7.5 mL, respectively. OS was analyzed in a Cox regression analysis using as covariates disease stage, PS and CTC before therapy or CTC decrease of at least 50% after the first cycle of chemotherapy. Results: A total of 41 pts with pathologically proven SCLC were included. Median (range) age was 66 yrs (47-84), male/female 26/15, PS 0/1/2/3 is 14/22/2/3, stage LD/ED 17/24, median (range) number of CTC is 9.5 (0-9909), 30 pts had ≥ 2 CTC at baseline. 33 pts were evaluable for CTC after one cycle of chemotherapy and 26 showed a decrease in CTCs of 50% or more. Median (range) OS was 240 days (219- 377). The predefined favorable prognostic group (baseline < 2 CTC count) was the most important prognostic factor (HR 3.3) after correction for age, sex, PS and stage. A decrease of at least 50% in CTC after one cycle of chemotherapy was the strongest prognostic factor (HR 0.015, 95%CI, 0.02-0.125, p < 0.0001) after correcting for baseline CTC, age, sex, PS and stage. Conclusions: Baseline CTCs and early decrease in CTCs in firstline chemotherapy are an independent predictive factor for OS in SCLC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Veridex/Immunicon Veridex LLC Veridex LLC
Ornithine Aminotransferase Turnover in Host Tissues of Tumor-Bearing Rats&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: K I Matthaei, J F Williams
Journal: JNCI Journal of the National Cancer Institute (1987)

The activity of ornithine-oxo-acid aminotransferase (OAT) in the liver and kidneys of rats was notably decreased as a consequence of tumor bearing. The decrease in the activity of OAT was closely related to a concomitant decrease in the rate of synthesis of the enzyme in both host tissues, while the rate of enzyme degradation remained unchanged. These results are concluded to be consistent with the proposal that host tissues of tumor-bearing animals may become “dedifferentiated,” and in this example the mechanism of the expression of the dedifferentiation involved the significant decrease in specific enzyme production.
Visualization of invasive breast cancer and its subclinical disease spread within the breast: Precise correlation between MR imaging findings and histopathologic findings
Authors: A. C. Schmitz, M. A. van den Bosch, C. Loo, J. L. Peterse, M. Gertenbach, W. P. Mali, E. J. Rutgers, K. G. Gilhuijs
Journal: Journal of Clinical Oncology (2009)

610 Background: Magnetic Resonance Imaging (MRI) of the breast shows superior ability to visualize the extent of invasive breast cancer compared to conventional breast imaging. Nonetheless, MRI may under- or overestimate the extent of invasive disease, and the ability of MRI to depict components of disease around the primary invasive tumor is not well established. The purpose of this study was to precisely correlate MRI findings with histopathologic findings in breast cancer patients and to establish the incidence and quantity of surrounding MRI occult disease in breast cancer patients that are scheduled for breast-conserving therapy (BCT). Methods: Patients were prospectively included if they had biopsy-proven invasive breast cancer and the choice of treatment was BCT after pre-operative MRI. Pathology findings were spatially reconstructed and correlated with preoperative MRI. Tumors were stratified by absence or presence of an extensive intraductal component (EIC- or EIC+). The largest diameter of the MRI-visible lesion was compared with the largest diameter of the primary invasive tumor at pathology. Distances (mm) between the edge of the MRI-visible lesion and surrounding subclinical tumor foci (i.e., DCIS, invasive foci) were measured. At various distances from the edge of the MRI-visible tumor, the incidence of disease was determined. Results: 53 patients with 54 breast tumors were included. 42 tumors were EIC- and 12 were EIC+. The mean size (± SD) of the primary invasive tumor was 18.1 ± 7.5 mm on MRI and 19.5 ± 8.2 mm on pathology (Pearson's correlation coefficient: 0.75). The MRI-visible lesion was larger than or equal to the primary invasive tumor on pathology in 21 (39%) cases. Underestimation of the primary invasive tumor occurred up to 7 mm from the edge of the MRI-visible lesion. Beyond 10 mm, subclinical tumor foci were found in 48% off all tumors, in 36% and 92% of EIC- and EIC+ tumors (p &lt; 0.001). Beyond 20 mm these rates were 19%, 7% and 67%, respectively (p &lt; 0.001). Conclusions: Disease around MRI-visible lesions may be more extensive than assumed prior to treatment, especially in EIC+ tumors. This may have consequences for treatment margins in MRI-guided therapy of localized breast cancer. No significant financial relationships to disclose.
Respiratory health, indoot air-pollution and asthma burden in school age children
Authors: Zorica Zivkovic, Sofija Cerovic, Jasmina Jocic-Stojanovic, Vesna Vekovic, Snezana Radic
Journal: European Respiratory Journal (2014)

Strong evidence is reported on risk factors from the indoor and outdoor environment on respiratory health in children.

The European Commission, funded the study on Schools Indoor Pollution and Health (SINPHONIE) carried out in 25 different European countries in winter season 2011/2012, during the heating season.

The aim of the study was to measure indoors and outdoors air-quality and level of pollutants and to correlate it with respiratory health. Since children spend a large part of their time at school, the initiatives to evaluate such indoor air quality (IAQ) were developed.

The study protocol included:questionnaire on school characteristics and IAQ policy; questionnaires derived from the International Study of Asthma and Allergies in Childhood, one filled in by the pupils and the other by their parents; school environmental assessments; and noninvasive clinical tests on a subsample of pupils.

Noninvasive clinical tests - spirometry, break-up time and tear film analysis, exhaled nitrogen oxide were performed. The selected schools were in urban and rural area.

Results: The pupils exposed to an elevated level of indoor pollutants showed higher prevalence of nonspecific respiratory symptoms. The exacerbation of asthma definitely correlates with higher levels of indoor pollution particularly during the winter season unrelated to school location, characteristics.

Conclusion: The indoor air quality directly affects the respiratory health of pupils in general while in asthmatic children may be a risk factor for the exacerbations and asthma attacks in school.

Brunekref B. Indoor environment. In:Annesi-Maesano I, Gulsvik A, Viegi G, eds. Respiratory Epidemiology in Europe. Eur Respir Mon 2000; 5: 384–399.
Relationship of glucose disorders and body mass index with pathologic complete response to neoadjuvant chemotherapy in breast cancer.
Authors: M. Cruz, S. Perez Alvarez, A. Armengol Alonso, E. Leon-Rodriguez
Journal: Journal of Clinical Oncology (2010)

e11048 Background: Literature documents the relationship between diabetes mellitus (DM) and obesity (OB) with poor outcome in breast cancer. On the other hand, larger retrospective studies support higher body mass index (BMI) with worse pathologic complete response (pCR) to neoadjuvant chemotherapy (NC). Methods: From January 1998 to December 2008, 119 patients were diagnosed with invasive breast cancer and treated with NC at Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. We analyzed age, hormonal status, BMI (WHO international classification), disorders of glucose (DoG) (ADA classification), histology, hormonal receptors, HER2/neu, type of NC and current use of metformin (MTF) to evaluate their association with pCR to NC. Results: Median age was 50 years. 20.0% had DM2, 7.6% impaired glucose tolerance and 49.7% OB. 34 patients with DoG, 67.6% were receiving treatment (8 MTF). The median BMI was 26.6kg/m2; 37% had overweight (OW) and 31.9% OB. 79.8% had ductal carcinoma. 21% were triple negative (TN), 50.4% positive estrogen receptors, 39.5% positive progesterone receptors and 23.5% positive HER2/neu. 3.4% had clinical stage I, 48.7% stage II, and 47.9% stage III. NC involved anthracyclines in 46.2%, taxanes and anthracyclines in 47.1%. pCR was obtained in 21 patients (17.7%). In the univariate analysis the number of cycles of chemotherapy (p = 0.043), lympho-vascular invasion (p = 0.011) and triple negative status (p = 0.024) were significantly more likely to have a pCR. In the multivariate analysis the only significant variable was TN status (p = 0.014). In the univariate and multivariate analysis, neither obesity, DoG nor treatment with metformin reach significance to predict pCR. Subgroup analysis (normal weight, OW and OB, and DoG) didn't demonstrate signficative differences in receptor status, HER2/neu or clinical stage. Conclusions: Our findings don't support the fact that BMI, DoG or use of metformin are predictors in the pCR to NC in breast cancer. Additional prospective studies to evaluate these factors and their association with pCR is warranted. No significant financial relationships to disclose.
Comparative Stability of the Agent of Chicken Tumor I in Citrate and Phosphate Buffers at 37° C
Authors: W. Ray Bryan, Mary E. Maver, John B. Moloney, Marguerite T. Wood, Carl L. White
Journal: JNCI Journal of the National Cancer Institute (1950)

Comparative Stability of the Agent of Chicken Tumor I in Citrate and Phosphate Buffers at 37° C W. Ray Bryan, W. Ray Bryan Search for other works by this author on: Oxford Academic PubMed Google Scholar Mary E. Maver, Mary E. Maver Search for other works by this author on: Oxford Academic PubMed Google Scholar John B. Moloney, John B. Moloney Search for other works by this author on: Oxford Academic PubMed Google Scholar Marguerite T. Wood, Marguerite T. Wood Search for other works by this author on: Oxford Academic PubMed Google Scholar Carl L. White Carl L. White National Cancer Institute, National Institutes of Healthy, U. S. Public Health Service, Bethesda, Md. With an Appendix by Jerome Cornfield, National Cancer Institute, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 11, Issue 2, October 1950, Pages 269–277, https://doi.org/10.1093/jnci/11.2.269 Published: 01 October 1950 Article history Received: 25 May 1950 Published: 01 October 1950
Solid Malignancies in Individuals With Down Syndrome: A Case Presentation and Literature Review
Authors: Scott V Bratman, Kathleen C Horst, Robert W Carlson, Daniel S Kapp
Journal: Journal of the National Comprehensive Cancer Network (2014)

Individuals with Down syndrome (DS) are at elevated risk for acute leukemia, whereas solid tumors are uncommon, and most types, including breast cancers, have significantly lower-than-expected age-adjusted incidence rates. This article reports on a man with DS and breast cancer, thought to be the first in the literature, and presents the management of his cancer. The literature on malignancies in patients with DS is reviewed and the major epidemiologic studies that have examined the spectrum of cancer risk in individuals with DS are summarized. Potential environmental and genetic determinants of cancer risk are discussed, and the potential role of chromosomal mosaicism in cancer risk among patients with DS is explored. Trisomy of chromosome 21, which causes DS, provides an extra copy of genes with tumor suppressor or repressor functions. Recent studies have leveraged mouse and human genetics to uncover specific candidate genes on chromosome 21 that mediate these effects. In addition, global perturbations in gene expression programs have been observed, with potential effects on proliferation and self-renewal.
Does Use of the Adjuvant! Model Influence Use of Adjuvant Therapy Through Better Risk Communication?
Authors: Jeffrey K. Belkora, David W. Hutton, Dan H. Moore, Laura A. Siminoff
Journal: Journal of the National Comprehensive Cancer Network (2011)

Adjuvant! is a model that provides recurrence and mortality risk predictions for patients with breast cancer considering adjuvant therapies. Although low-risk patients who saw Adjuvant! chose adjuvant therapy less frequently, whether this was because of educational or other aspects of the decision aid is unknown. The authors explored whether Adjuvant! affects choice of therapy through increased patient knowledge. A subset of data were analyzed from a cluster randomized trial in which oncology practices in 2 major United States cities were randomly assigned to use either Adjuvant! or an informational pamphlet to educate patients. Of 405 patients, 48 were low-risk, with 28 assigned to the decision aid and 20 to the pamphlet. Among the low-risk patients, using frequency tables and Fisher exact tests, the authors explored whether Adjuvant! was associated with more accurate patient estimates of survival; whether accuracy was associated with treatment choice; and whether, after controlling for accuracy, any remaining association was seen between Adjuvant! and treatment choice. Adjuvant! was associated with more accurate estimates of baseline prognosis compared with the pamphlet (57% vs. 25%; P = .04). Patients who had more accurate estimates of baseline prognosis were less likely to choose adjuvant therapy (62% vs. 89%; P = .04). After controlling for accuracy, no statistically significant association was found between the use of Adjuvant! and adjuvant therapy (P = .59 and P = .11 for inaccurate and accurate patients, respectively). Adjuvant! seems to influence patient choice through educational rather than other means of persuasion. However, many patients held inaccurate risk perceptions after viewing Adjuvant!.
Osteoporosis Overtreatment in a Regional Health Care System
Authors: Joshua J. Fenton, John A. Robbins, Anna Lee D. Amarnath, Peter Franks
Journal: JAMA Internal Medicine (2016)

This cohort study estimates the incidence of osteoporosis overtreatment of women in a health system where DXA reports include T scores for anatomic sites that guidelines recommend against using as a basis for treatment.
Predicting breast cancer risk from the interaction of multiple genetic polymorphisms
Authors: E. R. Jupe, J. J. Mulvihill, D. A. Ralph, C. E. Aston, D. P. Lalo, S. Manjeshwar, D. C. Defreese, B. A. Gramling, M. A. Craft, D. S. Mitchell
Journal: Journal of Clinical Oncology (2004)

9508 Background: The proportion of breast cancer attributable to germline mutations in highly penetrant genes (e.g., BRCA1/2) is small because of the low frequency of these mutations. Common, but weakly penetrant, functional genetic polymorphisms are likely to account for most of the genetic risk for breast cancer in the general population. Methods: Potential gene-gene interactions among ten genes, with known or predicted functional consequences in development of breast carcinoma, were examined in 1050 cases and 1845 controls of Caucasian descent. Association of breast cancer risk with variation in single genes and two- and three- gene combinations was analyzed for two age groups: 53 years and under, and over 53 years. The odds ratio (OR) for a genotype was calculated and compared to a null distribution of ORs generated for this genotype by randomizing (10,000 times in these analyses) the case-control status of the individuals in the sample to give an empirical estimate for the p-value of the observed OR. Re-sampling was used to give an empirical estimate of the 95% confidence interval and a likely more stable estimate of the OR for the genotype, particularly for the less common genotypes. In these analyses the population of individuals was resampled 10,000 times with each repetition composed of 80% of the controls and 80% of the cases selected at random from the whole sample. Results: Over 100 genotypes met stringent criteria for significance (α=1/10,000) with ORs ranging from 0.20 to 5.2, a 26-fold range. Single gene analyses were largely uninformative, whereas, the majority of the significant ORs were two- and three-gene combinations. Comparing observed ORs to ORs predicted by an independent gene model showed that about 25% of the significant multigenic combinations differed markedly from the predicted value. Conclusions: Combinations of genes interact to affect risk for breast cancer in a manner that is not predictable by combining the effects of the individual component genes. While independent genes are a valid starting point in a polygenic model, identifying and incorporating modification of risks associated with gene-gene interactions will improve accuracy of the model. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration InterGenetics, Inc. InterGenetics, Inc. InterGenetics, Inc. InterGenetics, Inc.
A prospective study of repeat endoscopic biopsy to identify HER2-positive tumors following an initial HER2-negative biopsy in unresectable or metastatic gastric cancer: Gasther-1.
Authors: Yoon-Koo Kang, Sook Ryun Park, Young Soo Park, Jeong Hoon Lee, Baek-Yeol Ryoo, Chang Gok Woo, Gin Hyug Lee, Hwoon-Yong Jung, Min-Hee Ryu
Journal: Journal of Clinical Oncology (2014)

27 Background: The intratumoral heterogeneity of HER2 expression in gastric cancer (GC) is a major challenge for identifying patients (pts) who would benefit from anti-HER2 therapy. The aim of this study is to evaluate the significance of re-evaluation of the HER2 status by repeat endoscopic biopsy in pts with HER2-negative GC on initial endoscopic biopsy. Methods: Pts with unresectable or metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma who would receive 1st line chemotherapy were eligible if the HER2 was negative on the initial endoscopic biopsy. HER2 positivity was defined as IHC 3+ or IHC 2+/FISH+ using the GC scoring system. A repeat endoscopic biopsy was performed in ≥6 different primary tumor sites immediately after obtaining initial HER2-negative results. Results: From May 2011 to April 2013, a total of 183 pts were enrolled. Baseline characteristics at the time of the initial biopsy were as follows: tumor location, GEJ~fundus/body~antrum/diffuse stomach = 22 (12.0%)/115 (62.9%)/46 (25.1%); Lauren classification, intestinal/diffuse/mixed = 53 (29.0%)/111 (60.7%)/19 (10.4%); and HER2 IHC score, 0/1/2 = 149 (81.4%)/26 (14.2%)/8 (4.4%). The median number of biopsy pieces was 5 (range, 1-15) and 10 (1-15) in the initial and repeat biopsy, respectively (p&lt;0.0001). As HER2 positive tumor was identified in 16 pts, HER2 positivity rate on repeat biopsy was 8.7% (95% CI 4.6-12.8%). The detection of HER2 positivity on repeat biopsy was associated with tumor location (diffuse stomach vs others = 0% vs 11.7%, p=0.013), Bormann type (IV vs others = 0% vs 11.7%, p=0.013), and the HER2 IHC score on the initial biopsy (0 vs 1/2 = 6.7% vs 18.2%, p=0.045). In multivariate analysis, the HER2 IHC score (1/2 vs 0, OR = 3.30; p=0.041) was an independent predictor of HER2 positivity in repeat biopsy. Conclusions: In pts with metastatic or unresectable GC, repeat endoscopic biopsy could detect HER2-positive GC which initial biopsy had missed. As anti-HER2 therapy improves the survival of pts with HER2 positive GC, in pts who showed HER2 negativity on initial biopsy, repeat biopsy should be considered subsequently.