tbuckley/cabot-search huggingface dataset:
Leukemia derived dendritic cells (LDCs) may be ineffective as a cancer vaccine for acute myeloid leukemia (AML)
Authors: J. Rosenblatt, R. Stone, Z. Wu, B. Vasir, D. Deangelo, I. Galinsky, K. Miller, J. D. Levine, R. Joyce, D. Avigan
Journal: Journal of Clinical Oncology (2005)

2527 Background: Dendritic cells generated from leukemic blasts (LDCs) are being explored as a strategy for generating anti-leukemia immunity. Optimizing this approach requires understanding the phenotypic and functional characteristics of LDCs. Methods: Leukemia blasts were isolated from peripheral blood of patients with AML. CD34 selection was performed on a subset of specimens. DCs were generated by culturing blasts in the presence of GM-CSF, IL-4 and TNFa for 7 days. LDC phenotype was analysed by flow cytometry, and was compared to fusions of leukemic blasts and allogeneic DCs derived from healthy donors. The capacity of LDCs to stimulate T cell proliferation and TH1 polarization was examined. Results: Compared to undifferentiated blasts, LDCs increased expression of HLA-DR and CD 11C (mean expression 77% and 62%). In contrast, LDCs did not strongly express costimulatory molecules CD80 or CD86 (mean expression 9% and 18%) or the maturation marker CD83 (mean expression 4%). In the subset of blasts that underwent CD34 selection, DC differentiation did not induce expression of CD 80, CD83, or CD86 (mean expression 6%, 2%, 9%). Culture of CD34- population with GM-CSF, IL-4 and TNFa resulted in moderate expression of CD 80, CD83 and CD86 (22%, 19.8% and 50.6% respectively). Of note, expression of tumor antigen CD117 (c-Kit) decreased after cytokine differentiation (mean expression 54% at baseline to 24% on LDCs). In contrast, fusion cells expressed both CD117 and CD86 (mean fusion efficiency 28%). Allogeneic T cell proliferation in response to stimulation by leukemic DC (mean SI 13.2, ratio 30:1) was higher than after stimulation with undifferentiated blasts (mean SI 6.8, ratio 30:1). However, neither stimulation with blasts nor with leukemic DC induced T cell expression of interferonγ. Conclusions: LDCs do not express costimulatory molecules and lose expression of tumor antigens, while fusion cells express both. LDCs stimulate allogeneic T cell proliferation but induce T cell expression of interferon gamma poorly. These results suggest that LDCs may be tolerogenic. Strategies to enhance the ability of LDCs to stimulate anti-tumor immunity are being explored, as are the functional properties of fusion cells. No significant financial relationships to disclose.
Health care utilization and costs associated with skeletal-related events (SREs) in patients with breast cancer (BC) and bone metastases (BMets).
Authors: May Hagiwara, Karen Chung, Thomas E. Delea
Journal: Journal of Clinical Oncology (2012)

72 Background: Patients with BMets secondary to BC are predisposed to SREs, defined as spinal cord compression (SCC), pathologic fracture (PF), surgery to bone (SB), and radiation therapy to bone (RT). Information on health care utilization and costs to treat SRE episodes in BC patients are limited. The objective of this study was to document current patterns of healthcare utilization and costs of SRE in patients with BC and BMets. Methods: This was a retrospective, observational study using the Thomson MedStat MarketScan Commercial Claims and Encounters database from 9/2002 to 6/2011. Study subjects included all persons with claims for BC (ICD-9-CM 174.xx) and for BMets (ICD-9-CM 170.xx or 198.5x), and ≥1 claim(s) for SRE. Key inclusion criteria included no other primary cancer and continuous enrollment ≥6 mos prior to BMets diagnosis. Unique SRE episodes were identified based on a gap of ≥90 days without an SRE claim, and classified by treatment setting (inpatient [IP, hospitalized for SRE during episode] or outpatient [OP]) and SRE type (SCC; PF [and no SCC]; SB [and no SCC or PF]; RT [and no SCC, PF, or SB]). Results: Of 22,709 BC patients with BMets, 11,941 had ≥1 SRE. Among 5,809 patients who met all other criteria, there were 7,617 SRE episodes over a mean (SD) follow-up of 17.2 (15.2) mos. The percent of SRE episodes that required IP treatment ranged from 11% (RT) - 76% (SB) (23% overall). On average, IP SCC episodes were most costly; while OP PF episodes were least costly. Of the total SRE costs (mean [SD] $21,072 [$36,462]/episode), 36% were for OP RT and 31% were for IP PF. Conclusions: In patients with BC and BMets, SREs are frequent and associated with high costs and hospitalizations. OP RT and IP PF account for a large share of SRE costs. Treatments that prevent SREs in these patients may reduce these costs. [Table: see text]
A Link Between Hypoglycemia and Progression of Atherosclerosis in the Veterans Affairs Diabetes Trial (VADT)
Authors: Aramesh Saremi, Gideon D. Bahn, Peter D. Reaven
Journal: Diabetes Care (2016)

OBJECTIVE To determine whether a link exists between serious hypoglycemia and progression of atherosclerosis in a substudy of the Veterans Affairs Diabetes Trial (VADT) and to examine whether glycemic control during the VADT modified the association between serious hypoglycemia and coronary artery calcium (CAC) progression. RESEARCH DESIGN AND METHODS Serious hypoglycemia was defined as severe episodes with loss of consciousness or requiring assistance or documented glucose &amp;lt;50 mg/dL. Progression of CAC was determined in 197 participants with baseline and follow-up computed tomography scans. RESULTS During an average follow-up of 4.5 years between scans, 97 participants reported severe hypoglycemia (n = 23) or glucose &amp;lt;50 mg/dL (n = 74). Serious hypoglycemia occurred more frequently in the intensive therapy group than in the standard treatment group (74% vs. 21%, P &amp;lt; 0.01). Serious hypoglycemia was not associated with progression of CAC in the entire cohort, but the interaction between serious hypoglycemia and treatment was significant (P &amp;lt; 0.01). Participants with serious hypoglycemia in the standard therapy group, but not in the intensive therapy group, had ∼50% greater progression of CAC than those without serious hypoglycemia (median 11.15 vs. 5.4 mm3, P = 0.02). Adjustment for all baseline differences, including CAC, or time-varying risk factors during the trial, did not change the results. Examining the effect of serious hypoglycemia by on-trial HbA1c levels (cutoff 7.5%) yielded similar results. In addition, a dose-response relationship was found between serious hypoglycemia and CAC progression in the standard therapy group only. CONCLUSIONS Despite a higher frequency of serious hypoglycemia in the intensive therapy group, serious hypoglycemia was associated with progression of CAC in only the standard therapy group.
Clinicopathological features and sites of recurrence according to breast cancer subtype in the National Comprehensive Cancer Network (NCCN)
Authors: N. U. Lin, A. Vanderplas, M. E. Hughes, R. L. Theriault, S. B. Edge, Y. Wong, D. W. Blayney, J. C. Niland, E. P. Winer, J. C. Weeks
Journal: Journal of Clinical Oncology (2009)

543 Background: Gene expression profiling has defined multiple breast cancer subtypes which can approximated using standard immunohistochemical markers. Methods: We assessed clinicopathological features and sites of recurrence for patients (pts) presenting to NCCN sites with stage I-III breast cancer from Jan 2000 to Dec 2006 where estrogen receptor (ER), progesterone receptor (PR), and HER2 status were known. Tumors were grouped as luminal A (ER+ and/or PR+, and HER2-), HER2+ (any ER or PR, and HER2+), or triple-negative (ER-, PR-, and HER2-). Chi-square compared proportions across tumors; univariate logistic regression estimated risk of first site of recurrence. Results: 12,858 pts met inclusion criteria. Median follow-up from NCCN presentation was 3.2 years. Subtype distribution was: triple-negative (TN) 17%; HER2+ 18%; luminal A 66%. Compared to pts with luminal A and HER2+ tumors, TN were younger (p&lt;0.0001), more likely African-American (p&lt;0.0001) and overweight (p=0.0006). TN and HER2+ tumors were less often detected by screening mammography (TN, 28.9%; HER2+, 33.6%; luminal A, 48.4%) and less likely to present as T1 (TN, 46.5%; HER2+, 50.5%; luminal A, 67.0%) or diagnosed as stage I (TN, 32.6%; HER2+ 33.2%; luminal A, 49.4%) than luminal A (all p&lt;0.0001). Rate of node positivity was lowest in TN (TN, 37.1%; HER2+, 44.9%; luminal A, 38.1%; p&lt;0.0001). 83% of TN tumors were high grade; 93% were invasive ductal histology. Extensive intraductal component and lymphovascular invasion were more often associated with HER2+, compared to TN or luminal A (p&lt;0.0001). Recurrences were recorded for 1,235 pts. Relative to luminal A, TN and HER2+ were more likely to experience lung (TN, odds ratio [OR] 2.27, 95% confidence interval [CI] 1.50, 3.43; p=0.0001; HER2+, OR 1.65, 95% CI 1.05, 2.60; p=0.03) and brain (TN, OR 5.32, 95% CI 2.85, 9.91; p&lt;0.0001; HER2+, OR 5.53, 95% CI 2.93, 10.43; p&lt;0.0001) as first site of recurrence; bone was less likely (TN, OR 0.23, 95% CI 0.16, 0.33; p&lt;0.0001; HER2+, OR 0.38, 95% CI 0.28, 0.53; p&lt;0.0001). Conclusions: Clinicopathological features and patterns of recurrence differed significantly by subtype and may inform the design of future clinical trials. No significant financial relationships to disclose.
Ikaros Mutation Confers Integrin-Dependent Survival Of Pre-B Cells and Progression To Acute Lymphoblastic Leukemia
Authors: Nilamani Jena, Ila Joshi, Toshimi Yoshida, Xiaoqing Qi, Jiangwen Zhang, Katia Georgopoulos, Richard A. Van Etten
Journal: Blood (2013)
New aspects in the treatment of cervical cancer complicated by pregnancy: Laparoscopic nodal evaluation before oncologic treatment delay.
Authors: G. Favero, V. Chiantera, A. Oleszczuk, V. Galotta, H. Hertel, J. Herrmann, C. Köhler, A. Schneider
Journal: Journal of Clinical Oncology (2010)

5062 Background: Cervical cancer is the most frequently encountered malignancy during pregnancy. The presence of nodal metastasis is the most important negative predictor factor and its assessment represents a crucial parameter to decide if the pregnancy can safely continue. We describe the results of 18 pregnant patients with cervical cancer who have their nodal status accessed by means of laparoscopy. Methods: Eighteen patients undergoing laparoscopic pelvic lymphadenectomy during pregnancy at Charité – Universitätsmedizin Berlin and Friedrich-Schiller-Universität Jena between 1999 and 2009 were included. Results: The mean age at diagnose was 32 years-old (26–40) and gestational age was between 6 and 23 weeks of pregnancy. The FIGO stage of cervical cancer was between 1a1 and 2a (1a1 for two women, 1a2 for one woman, 1b1 for thirteen women, 1b2 for one woman and 2a for one woman). The histologic type was SCC in nine cases and adenocarcinoma also in nine cases. All of the laparoscopic procedures were successful; there was no mortality, morbidity, or conversion. There were no complications for either mother or child related to the general anesthesia. The mean number of lymph nodes removed was 17 (6-46). Cancer treatment was delayed for fourteen out of eighteen patients until after delivery, during an average time of 17 ( 9-28) weeks. Lymph nodes were positive in three cases and these patients received immediate cancer treatment. One patient decided to interrupt the gestation before delivery even with negative nodes. All patients were alive without recurrence at a mean follow-up time of 36 (3-126) months. Eleven patients out of fourteen reached fetal maturity and gave birth by caesarean section to healthy babies, and 3 still are in the course of gestation. Conclusions: We could demonstrate the feasibility and the safety of laparoscopic pelvic lymphadenectomy during pregnancy and no complications neither to mothers nor to infants were observed. We showed that when cervical cancer complicates gestation, a planned delay of oncologic treatment can be considered a safe option after tumor metastasis to lymph nodes has been histopathologically ruled out. No significant financial relationships to disclose.
Delivered relative dose intensity and febrile neutropenia rate with common adjuvant chemotherapy regimens: A review
Authors: M. S. Raza, J. Younus, S. Welch
Journal: Journal of Clinical Oncology (2008)

11505 Background: Adjuvant chemotherapy for early-stage breast cancer decreases the risk of recurrence and improves survival. Prior work has pointed out that <85% of relative dose intensity (RDI) could result in compromised outcome. Methods: Among consecutively treated patients, one hundred patients treated with (AC-T) doxorubicin, cyclophosphamide (4 cycles) followed by paclitaxel (4 cycles), one hundred patients treated with (FEC-D) 5FU, epirubicin and cyclophosphamide (3 cycles) followed by docetaxel (3 cycles) and 75 patients treated with (FEC100) 5FU, epirubicin and cyclophosphamide (6 cycles) were retrospectively analyzed. Summation dose intensity (SDI) is used as a reference for RDI. To calculate SDI of each regimen, a unit dose intensity (UDI) of each drug in the combination regimen is calculated, defined as the dose of the drug required to produce 30% complete plus partial response when used as a first-line single agent in metastatic breast cancer. The dose intensity of each drug in a combination is expressed as a fraction of that drug’s UDI and fractions for all the drugs are added together. The incidence of FN was recorded as well. Results: Almost 30% of patients receiving FEC-100, 4% with AC-T and 10% with FEC-D were over 65 years. Only 4% with AC-T, 5% with FEC-D but 21% patients receiving FEC-100 had <85% RDI. About 1/3rd of FEC-100 patients but 63% of AC-T and 77% patients of FEC-D had 100% of RDI delivered. FN rates were 7% for AC-T and 23% for FEC-D. Almost all FN cases were seen with the dose of Docetaxel (19/23) in patients receiving FEC-D. Conclusions: To our knowledge, delivered RDI and/SDI for these regimens have not been reported previously and the results show the experience of an academic cancer centre. The delivered RDI for AC-T and FEC-D is excellent but for FEC-100 is sub-optimal. This variability could be due to a smaller sample, relatively elderly population and various other factors. Although the FN rate for AC-T appears to be similar as previously reported, the FN rate for FEC-D is higher. This higher rate combined with the fact that the most FN cases occurred with docetaxel appears to reflect the experience for the patients outside the clinical trial. No significant financial relationships to disclose.
A phase I study of AGRO100 in advanced cancer
Authors: D. A. Laber, M. A. Choudry, B. S. Taft, L. Bhupalam, V. R. Sharma, F. J. Hendler, K. M. Barnhart
Journal: Journal of Clinical Oncology (2004)

3112 Background: AGRO100 is an oligonucleotide that functions as an aptamer and binds to nucleolin, a protein found intranuclear in all cells, but uniquely expressed on the surface of tumor cells. Such binding leads to internalization of the complex, and a strong anti-proliferative response in the tumor cell. Methods: Objectives are toxicity, pharmacokinetics and preliminary responses. AGRO100 was administered as continuous intravenous infusion over 96 hours in the hospital. Dose level 1 was 1 mg/kg/day. Patients were enrolled in cohorts of 3. If no toxicity was observed 28 days after therapy, the dose of AGRO100 was doubled. Toxicity was graded by the NCI CTCAE v3.0. Responses were assessed every 28 days by using the RECIST guidelines. Results: From September 2003 through December 2003, 9 patients with advanced cancer were enrolled. Prior to AGRO100 treatment, all patients had objective documentation of progressive metastatic disease after multiple therapies. Patient characteristics: 9 patients are evaluable for toxicity and 6 for response. 13 cycles of AGRO100 have been administered (1–2 cycles/patient). 4/6 patients had stable disease after 1 treatment and received a second course. 2/6 patients progressed after 1 cycle. No toxicity of any type has been observed. AGRO100 was present in the serum during the entire infusion and the concentration was related to the dose. Further dose escalation is ongoing. Conclusions: AGRO100 is the first nucleic acid aptamer ever tested for the treatment of cancer in humans. This non-toxic targeted cancer therapy achieved stable disease in 67% of the patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aptamera, Inc. Aptamera, Inc.
Prognostic features and outcome in patients with agressive non-Hodgkin’s lymphoma who do not achieve a complete response to first-line regimens
Authors: S. Alici, S. Bavbek, M. Basaran, H. Onat
Journal: Journal of Clinical Oncology (2005)

6737 Background: To retrospectively identify the prognostic factors that specifically predict survival rates of patients with aggressive non-Hodgkin lymphoma (A-NHL) who did not achieve a complete response (CR) to first-line therapy. Methods: The current study was comprised of 76 patients [41 females and 35 males with a median age of 60 years (range:18 to 87 years)] with initial treatment (doxorubicin-containing regimens in 92% of cases) from a series of 200 patients consecutively diagnosed with A-NHL at the Institute of Oncology, Istanbul University between 1989–1998. Initial variables, response to therapy, and salvage treatment were analyzed to predict survival. Results: Median age was 60 years (range: 18–87 years) and the male: female radio was 0.85. The median follow-up was 14 months (range: 1–120 months). The median survival was 15 months (range: 11–19 months). Five-year overall survival rate was 25%. Among the 27 patients with primary refractory disease, 20 died during initial treatment due to toxicity or disease progression. The median survival for this group of patients was 7.6 months (range: 5.7–9.4 months) and the 2-year overall survival rate was 19.8%. Ten of these 27 patients were able to receive salvage regimens, with only 1 of them achieving a CR. With regard to those patients achieving a partial response, 14 of the 49 patients received further therapy with 4 of them achieving a CR. In a univariate analysis, the following variables were associated with prognosis in term of survival: histological grade of tumor, degree of response, PS, and International Prognostic Index risk groups. Cox multivariate regression analysis showed that primary refractory disease and high grade histology were the factors associated with shorter survival. Conclusions: The prognosis of primarily refractory patients is extremely unfavorable, whereas that of patients who achieve a partial response is slightly better. The inclusion of these patients in experimental trials is limited due to their tendency to be of an older age and to have a poor general status. No significant financial relationships to disclose.
Studies on the Mechanism of Isoantigenic Variant Formation in Heterozygous Mouse Tumors. I. Behavior of &lt;italic&gt;H-2&lt;/italic&gt; Antigens D and K: Quantitative Absorption Tests on Mouse Sarcomas&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Eva Klein
Journal: JNCI Journal of the National Cancer Institute (1961)

Previous studies on the MSWB sarcoma of (A × A.SW)F1 origin have shown that its cells contained antigens D and K of the H-2 system. It was possible to select isoantigenic variants in appropriate animal hosts. These hosts either lacked K but contained D, or lacked D but contained K. There were two types of variants isolated, as judged by their transplantation characteristics—they either behaved as if they had lost K and still contained D, or had lost both D and K. It was impossible to isolate a third type, which behaved like it had lost D but still had K. This paper extends these results to 3 tumors of (A × A.SW)F1 origin and 2 of (A × A.CA)F1 origin. A total of 33 variants was isolated. The transplantation data were in full agreement with the previous preliminary findings. Furthermore, the variants were analyzed for the actual presence of antigens D and K in their cells by a quantitative absorption technique. The serologic analysis completely agreed with the expectations based on the transplantation tests. For correct interpretation of the data, it was essential to exclude possible antigenic contribution of host cells. This was done by using newborn, irradiated hosts containing neither D nor K. One possible explanation of these findings is that isoantigenic variant formation is based on a mechanism involving mitotic crossing over, but further studies are required to establish this definitely.
Role of endocrine responsiveness and adjuvant therapy in very young women (&lt; 35 years) with operable breast cancer and node negative disease
Authors: L. Orlando, A. Cardillo, R. Ghisini, N. Rotmensz, G. Peruzzotti, P. Maisonneuve, G. Viale, A. Goldhirsch, M. Colleoni
Journal: Journal of Clinical Oncology (2006)

558 Background: Breast cancer rarely occurs in young women. There is limited knowledge about prognosis, and treatment effects in the population with node negative disease, largely dependent upon older series and extrapolation of data from older age cohorts. Methods: We evaluated biological features and adjuvant treatment recommendations for 841 premenopausal consecutive patients with pT1–3, pN0 and M0, operated and counseled for medical therapy from April 1997 to December 2001. We evaluated also, the prognostic role of age and adjuvant treatment. Median follow-up was 49.9. Results: Very young women (101, 12%) were more likely to have tumors with absent ER (42% v 17.6%, p &lt; .0001) and PgR (48% v 23.2%, p &lt; .0001), &gt; 2 cm (36.7% v 24.8%; p = .002), grade 3 (53.9% v 33.5%; p = .0009) and elevated Ki-67 (68.5% v 51.6%; p = .002), when compared with older patients (740, 88%). Younger patients (compared with older patients) with endocrine responsive disease were prescribed more chemotherapy (67.2% v 44.3%; p = .0009) but endocrine adjuvant therapy was prescribed in a similar percentage in both groups (93.1% v 96% p = .30). A statistically significant difference in disease-free survival (DFS), risk of distant metastases and overall survival (OS) was observed at the multivariate analysis for younger patients (HR = 4.44; 95% CI, 2.53 to 7.78, p &lt; .0001 for DFS; HR = 3.23; 95% CI, 1.32 to 7.94, p = .011 for distant metastases; HR = 2.89; 95% CI, 1.06 to 7.87, p = .038 for OS). An increased risk for younger age was observed for patients with endocrine responsive disease (ER ≥ 1%) (HR = 5.17; 95% CI, 2.72 to 9.83, p &lt; .0001 for DFS) in particular if endocrine therapy was not performed (HR = 7.77; 95% CI, 1.98 to 30.6, p = .003 for DFS). Conclusions: We conclude that compared with less young premenopausal patients, the very young women presenting with breast cancer and ipsilateral axilla negative for disease, are at larger chance of relapse. Endocrine therapies are crucial in patients with endocrine responsive disease. No significant financial relationships to disclose.
Tissue Engineering: Electroconductive Nanopatterned Substrates for Enhanced Myogenic Differentiation and Maturation (Adv. Healthcare Mater. 1/2016)
Authors: Hee Seok Yang, Bora Lee, Jonathan H. Tsui, Jesse Macadangdang, Seok‐Young Jang, Sung Gap Im, Deok‐Ho Kim
Journal: Advanced Healthcare Materials (2016)

Engineering mature and functional skeletal muscle tissue requires an ability to promote the structural organization and differentiation of cultured myoblasts. On page 137, D.-H. Kim, S.G. Im, and co-workers describe a bio-inspired electroconductive culture platform, wherein a nanopatterned substrate mimicking the extracellular matrix of native muscle tissue is covered with a thin layer of gold. Engineered tissues using this platform feature hypertrophic and uniaxially aligned myotubes with increased expression levels of myogenic markers.