tbuckley/cabot-search huggingface dataset:
The correlation of thrombin-activated fibrinolysis inhibitor (TAFI) levels and clinicopathologic factors in advanced colorectal cancer patients
Authors: T. Salman, A. Bilici, B. O. Ustaalioglu, M. Seker, B. Sonmez, M. Gumus, T. Salepci, M. Yaylaci, A. Orcun, A. Mayadagli
Journal: Journal of Clinical Oncology (2009)

e22217 Background: There are many ongoing researchs for novel prognostic factors in colorectal cancers. Increased thromboembolic events were associated with poor prognosis and survival in cancer patients. Thrombin-activated fibrinolysis inhibitor (TAFI), which has inhibitory effects on fibrinolysis, was proven to play a major role in hypercoagulopathy and was reported to reach high blood levels in cancer patients compared to those in the general population. Methods: TAFI levels were measured. The correlation between those levels and clinicopathologic features were analyzed in 82 patients with advanced stage colorectal cancer receiving treatment in our clinic. Results: Eighty-two patients were evaluated. Patients characteristics included 54 males (65.9%), 28 females (34.1%); median age 56.4 (range:24–76). The mean TAFI levels was 198,36±70,01 Ğer yazali and TAFI levels were found to be high in 70% of patients. High levels of TAFI were more common in rectum cancer patients compared with colon cancer patients. There was no significant correlation between TAFI levels and clinicopathologic factors, such as age, sex, body mass index, performance status, number of metastases, grade, vascular invasion, perineural invasion and CEA levels. The TAFI levels of patients receiving bevacizumab (202.1±66.6) were more higher than those no receiving (191,83±76,21), but this association was not statistically significant (p&gt;0.05). Conclusions: Although the statistical analysis proved insignificant in our study, the effect of thromboembolic events on prognosis and survival is well established. Thus, large scale prospective studies are required to determine prognostic factors. No significant financial relationships to disclose.
The impact of multiple primary cutaneous melanomas on survival of 2,942 patients with metastatic melanoma.
Authors: R. Murali, P. T. Brown, R. Kefford, J. F. Thompson, M. B. Atkins, G. V. Long
Journal: Journal of Clinical Oncology (2010)

8540 Background: A history of multiple primary melanomas (PM) is associated with improved survival in patients with early-stage melanoma. Patients with multiple PM are excluded from most large staging and prognostic analyses (e.g. AJCC 7th edition) as their impact on survival is poorly understood and difficult to study. We sought to determine if the number of cutaneous PM is an independent predictor of survival in patients with metastatic melanoma (MM). Methods: Patients with MM diagnosed between 1983 and 2008 were identified in the prospectively maintained Melanoma Institute Australia database. The cutaneous PM responsible for metastasis (culprit PM) was assigned using a predefined structured algorithm. Overall survival (OS) was calculated from date of first distant metastasis. Survival analysis was carried out using the Kaplan-Meier method and log-rank test. A multivariate Cox proportional hazards model was used to identify independent predictors of OS. Results: Of a total of 2,942 patients with MM, 2634 (89.5%) had 1 PM and 308 (10.5%) had > 1 PM. Factors that were independently predictive of shorter OS were site of metastases (brain vs. lymph node/subcutaneous/soft tissue [HR 2.41, 95% CI 2.07-2.81, p < 0.001]; non-lung viscera vs. lymph node/subcutaneous/soft tissue [HR 1.92, 95% CI 1.67-2.22, p < 0.001], age > 60 years [HR 1.23, 95% CI 1.12-1.36, p < 0.001], shorter disease-free interval (DFI) from culprit PM to first distant metastasis [≤ 12 vs. > 36 months; HR 1.62, 95% CI 1.39-1.89, p < 0.001] and fewer PM [1 vs. > 1; HR 1.26, 95% CI 1.08-1.47, p = 0.004]. Factors not independently prognostic were gender, frequency of follow-up visits during DFI, decade of diagnosis of MM and features of the culprit PM (site, thickness, mitotic rate, ulceration and decade of diagnosis). Conclusions: A history of multiple cutaneous PM is an independent prognostic factor for improved survival in patients with MM. Once metastasis occurs, characteristics of the PM have no impact on outcome, but patients with multiple PM may have different mechanisms of melanoma genesis and evolution that persist to influence metastatic behavior. Multiple PM should be considered when planning large staging and prognostic studies of melanoma. No significant financial relationships to disclose.
Analysis of plasma proteome from BRCA1/BRCA2 mutation carriers as modifier risk factor of breast cancer.
Authors: A. Custodio, P. Pérez-Segura, J. Zamorano, A. López-Farrã, E. Olivera, J. Puente, E. Diaz-Rubio
Journal: Journal of Clinical Oncology (2010)

1549 Background: BRCA1/2 mutations were estimated to cause cumulative lifetime risk of breast cancer of 70% by 70 years. However, there is a marked variation of phenotypic expression among carriers. Identification of markers to refine estimates of a woman's individual cancer risk remains challenging in order to individualizing prevention strategies. This study represents the first attempt to evaluate by proteomic research differentially expressed plasma proteins in BRCA1/2 carriers respect to a control group and in cancer patients (CP) when compared to cancer-free carriers (CFC). Methods: We use two-dimensional gel electrophoresis and mass spectrometry to analyze plasma levels of the following proteins in 42 BRCA mutation carriers (22 BRCA1- 10 CP and 12 CFC- and 20 BRCA2- 12 CP and 8 CFC): fibrinogen (fgg), haptoglobine (hap), serotransferin (ser), convertase (con), alpha1-antitrypsin (AAT), apolipoprotein A-I (APO AI) and A-IV (APO AIV) and C-reactive protein (CRP). The control group included 10 age-matched non-carriers without personal or family history of cancer. PD-QUEST software was used to determine the total protein count for each group. Results: AAT 4 (p = 0.038), 5 (p = 0.023) and 6 (p = 0.037), hap 4 (p = 0.023) and APO AI 2 (p = 0.038) and 5 (p = 0.013) were increased in BRCA2 carriers respect to BRCA1 ones. BRCA1 CFC showed higher levels of AAT 6 (p = 0.046) and APO AIV (p = 0.004) than BRCA1 CP. No significant differences were found between BRCA2 CP and CFC. BRCA2 CP when compared to BRCA1 showed increased levels of AAT 6 (p = 0.023), APO AI 2 (p = 0.038) and 5 (p = 0.019) and APO AIV (p = 0.010) and decreased levels of con 3 (p = 0.023). Fgg 2 (p = 0.001) and 3 (p = 0.001), ser 4 (p = 0.001) and con 2 (p = 0.006), 3 (p = 0.001) and 4 (p = 0.001) were found significatively increased in CFC respect to the control group. No significant differences were found in the total protein count among groups using PD-QUEST. Conclusions: Proteomic analysis makes it possible to develop a map of proteins isoforms that are differentially expressed in plasma of BRCA CP and CFC as well as in a control group. The confirmation of these results in a larger cohort is required before proteomic analysis could be used to guide prevention strategies among BRCA carriers. No significant financial relationships to disclose.
Integrated whole genome and transcriptome analysis identified a therapeutic minor histocompatibility antigen encoded by an alternative ITGB2 transcript
Authors: Margot J Pont, Dyantha van der Lee, Edith van der Meijden, Cornelis van Bergen, Michel Kester, Maria Honders, Martijn Vermaat, Matthias Eefting, Erik Marijt, Szymon Kielbasa, Peter-Bram 't Hoen, Frederik Falkenburg, Marieke Griffioen
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Patients with hematological malignancies can be successfully treated with allogeneic stem cell transplantation (alloSCT). In HLA-matched alloSCT, donor T cells can mediate desired anti-tumor immunity as well as undesired side effects by recognizing minor histocompatibility
Molecular portraits of mammographic breast density in normal breast tissue
Authors: W. Yang, A. A. Sahin, H. Wong, A. Tsimelzon, K. Hess, N. Karadag, M. Cairo, F. Meric, B. Arun, J. C. Chang
Journal: Journal of Clinical Oncology (2008)

22227 Background: High mammographic density is associated with a 6-fold increased risk of breast cancer. Pathways responsible for this increased density are unknown. We hypothesize that specific molecular pathways exist that are associated with increased mammographic density and breast cancer risk. Methods: Histologically confirmed normal breast tissue was collected from women undergoing breast surgery who had available demographic data and mammograms for review. Breast parenchymal density was classified according to the American College of Radiology's Breast Imaging - Reporting and Data System reporting system. Quantitative classification of mammographic parenchyma was performed using thresholding method and percent density. Women with low (less than 50%) versus high (greater than 50%) breast density were compared. Double-stranded cDNA was synthesized from the normal breast tissue using an oligo-dT primer containing a T7 RNA polymerase promoter, followed by in vitro transcription with biotinylated ribonucleotides. The labeled cRNA was hybridized to Affymetrix HG U133Plus2 chips which comprise ∼28,600 genes to determine gene expression patterns. Results: Sixty-two women were identified, 26 (42%) had high, and 36 (58%) had low mammographic density. Neither menopausal nor hormone receptor status influenced the gene expression pattern. 841 genes had differential expression between normal breast tissue with high and low mammographic density (p<0.01, fold change >1.2) and had a low false discovery rate (<10%). Of these 841 differentially expressed genes, the most significant canonical pathways up-regulated in dense normal breast tissue included the Notch (DLK1), Wnt (FZD10), and insulin receptor growth signaling (IGFBP1), which are known regulators of normal mammary stem cell self-renewal. In addition, genes governing alternative splicing were increased, including a non-coding RNA (MALAT1, TncRNA), and RNA splicing factors (SFRS1, SFRS3 SFRS4, and SFRS7). Conclusions: Specific pathways, including those involved in normal stem cell self-renewal and with epigenetic regulation, may influence breast density and hence, breast cancer risk. Understanding these pathways could lead to early chemopreventive interventions in high-risk women. No significant financial relationships to disclose.
Bevacizumab and pegylated liposomal doxorubicin as first-line therapy for locally recurrent or metastatic breast cancer: A multicenter, single-arm phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)
Authors: C. Rochlitz, C. Spirig, T. Ruhstaller, T. Suter, M. Bühlmann, M. Fehr, A. Schönenberger, S. Lerch, M. Mayer, K. Zaman
Journal: Journal of Clinical Oncology (2009)

1030 Background: Bevacizumab in combination with taxanes has become a standard first-line treatment of advanced breast cancer in some countries, but there is no information on its use in combination with pegylated lipsomal doxorubicin in metastatic breast cancer. Therefore, we performed a multicenter, single-arm phase II trial to evaluate the toxicity and efficacy of pegylated liposomal doxorubicin (PLD) and bevacizumab (B) as first-line treatment in advanced breast cancer. Methods: PLD at a dose of 20 mg/m 2 and B at 10 mg/kg were infused on days 1 and 15 of each 4-week cycle for a maximum of 6 cycles. Thereafter, B monotherapy was continued at the same dose until progression or toxicity. Primary endpoint was the occurrence of specific toxic events known to strongly interfere with quality of life, i.e., severe cardiac toxicity, any grade 4/5 toxicity, and selected grade 3 nonhematological toxicities (hand-foot-syndrome, cognitive disturbance, CNS hemorrhage, and mucositis/stomatitis). Secondary endpoints included overall response, progression free survival (PFS), time to treatment failure, and duration of response. Eligibility criteria included documentation of metastatic or inoperable breast cancer; measurable disease according to RECIST; erbB2-negativity; LVEF of ≥ 55%; WHO performance status 0 or 1. The study used a Herndon's two-stage design with 14 and 29 patients for stages 1 and 2, respectively. The promising rate of primary toxicity was &lt;15% and the uninteresting rate &gt;33%. The type I error probability was 5% and the power 80%. Results: The trial had to be stopped prematurely because of toxicity after the enrollment of 41 evaluable patients. Among these patients, 16 (39%) had grade 3 hand-foot syndrome, 1 grade 3 mucositis and 1 grade 4 cardiac toxicity. Thus, a total of 18/41 (44%, exact 95% c.i. 28–60%) of all patients had a primary toxicity. Best overall response rate was 23.3% (exact 95% c.i. 12–39%), median PFS was 7.5 months (95% c.i. 4.6–8.1 months). Conclusions: The combination of 2-weekly PLD and B in advanced breast cancer is surprisingly toxic and only modestly active and should not be further investigated. [Table: see text]
Tumor VEGFA gene expression is associated with serum lactate dehydrogenase (LDH) levels and intratumoral mRNA expression of genes involved in glycolysis in patients with metastatic colorectal cancer (mCRC)
Authors: M. Azuma, M. M. Shi, C. J. Jacques, C. Barrett, K. D. Danenberg, S. Iqbal, A. El-Khoueiry, D. Yang, W. Zhang, H. Lenz
Journal: Journal of Clinical Oncology (2006)

3530 Background: It is well known that angiogenesis and glycolysis are regulated by hypoxic conditions. Recent clinical trials (CONFIRM1 and CONFIRM2) have shown that patients with mCRC with high serum LDH benefited from PTK787/ZK 222584, a VEGF receptor tyrosine kinase inhibitor. We tested the hypothesis that patients with high serum LDH have increased intratumoral expression of genes involved with hypoxia (hypoxia inducible factor (HIF1a and 2a) and lactate dehydrogenase A (LDHA) and glycolysis (glucose transporter 1 (Glut-1) and genes involved in angiogenesis such as vascular endothelial growth factor A (VEGFA) and neuropilin 1 (NRP1) in patients with mCRC. Methods: 78 formalin fixed paraffin embedded (FFPE) tumor samples from 36 patients (20 males, 16 females: Median age 59 years (range 29–84) with mCRC who underwent first line therapy (not from CONFIRM trials) were analyzed. In addition, tumor gene expression was correlated with serum LDH levels from the same group of patients. FFPE tissues were dissected using laser-captured microdissection and analyzed LDHA, VEGFA, HIF1a, HIF2a, Glut-1 and NRP1 mRNA expression using a quantitative real-time RT-PCR method. Gene expression values (relative mRNA levels) are expressed as ratios between the target gene and internal reference gene (beta-actin). Results: Spearman Rank Correlation Analysis of Associations Between serum LDH levels and Gene Expression values. Conclusions: Our results demonstrate that intratumoral gene expression of LDHA, HIF1a and HIF2a, Glut-1 and VEGFA are significantly correlated. Patients with high serum LDH have increased intratumoral gene expression of VEGFA. These results support the hypothesis that serum LDH levels may serve as a surrogate marker for activation of the HIF related genes in the tumor. These observations may explain the efficacy of PTK787 in metastatic colorectal cancer patients with high serum LDH levels. [Table: see text] [Table: see text]
Impact of trastuzumab on the pathological complete response (pCR) rates in primary systemic therapy for breast cancer
Authors: N. Mizuta, H. Nakajima, K. Sakaguchi, Y. Hachimine, I. Fujiwara
Journal: Journal of Clinical Oncology (2007)

11000 Background: Various regimens of primary systemic therapy (PST) have been performed to patients with locally advanced breast cancer to decrease the size of the primary tumor and allow for effective local and distant control. In terms of pathological complete response (pCR) rate, however, satisfactory results were not obtained. Therefore, in this study, we have tried to determine whether the addition of trastuzumab on PST could increase pCR rate. Methods: Two prospective nonrandomized studies were performed that used different regimens as PST, followed by breast conserving surgery. Group-A ; Eighty-fore HER2-negative patients with operable breast cancer were assigned to 4 cycles of epirubicin and cyclophosphamide followed by 12 cycles of weekly paclitaxel. GroupB; Eighteen HER2-positive patients were assigned to 4 cycles of epirubicin and cyclophosphamide followed by 12 cycles of weekly paclitaxel and trastuzumab. Results: A total of 102 assessable patients were enrolled, and all the patients have completed the above 2 regimens of PST. Pathological complete response (pCR) rates were 12% in Group-A and 61.1% in Group-B, respectively. Following the PST, 75% of Group-A and all of Group-B patients were able to be subjected to breast conserving surgery. All the toxicities happened in both groups were well controlled in grade 1 or 2. Conclusion: These results indicate that both the PST regimens were safely performed in women with locally advanced breast cancer and allow breast conserving surgery in a high fraction of patients (90%). In addition, significantly high rates of pCR were obtained in patients with use of trastuzumab (p&lt;0.01). No significant financial relationships to disclose.
Feasibility study on radiofrequency ablation therapy followed by partial mastectomy for stage I breast cancer patients
Authors: S. Imoto, N. Wada, N. Sakemura, Y. Murata, T. Hasebe
Journal: Journal of Clinical Oncology (2008)

11583 Background: Breast-conserving surgery (BCS) is a standard care for early breast cancer patients. However, local control is not sufficient for surgery alone and breast irradiation and hormonal treatment in hormone-sensitive tumor should be recommended to reduce 10% or less of local failure rate. To evaluate the safety and reliability of thermal ablation therapy instead of BCS, we performed radiofrequency ablation therapy (RFA) for stage I breast cancer patients. Methods: Thirty female breast cancer patients with no extensive intraductal spread were enrolled. Under general anesthesia, sentinel node biopsy, and then RFA immediately followed by BCS was performed. Resected specimens were examined at 5 mm intervals by hematoxylin-eosin (HE) staining and several slices of tumor and non tumor lesions in each case were also evaluated by nicotinamide adenine dinucleotide (NADH) diaphorase staining. Results: Tumor diameters with breast ultrasound ranged from 0.9 cm to 2.4 cm. RFA-relating adverse events were observed in 2 cases of grade 2 skin burn and 7 cases of unclassified burn in major pectral muscle. There was one case of technical failure due to inadequate electrode replacement into the tumor. Twenty-eight cases (93%) revealed pathological degeneration changes of tumor specimens in HE staining. In 24 of the 26 cases (92%) examined by NADH diphorase staining, tumor viability was completely diagnosed as negative. As 2 cases had extensive intraductal component beyond ablated lesions, the overall success rate of RFA was 87% (26/30). Conclusions: RFA proved to be reliable and feasible in stage I breast cancer without extensive intraductal component. RFA will be an alternative to BCS as surgical treatment. The phase II trial of RFA alone is being planned now. No significant financial relationships to disclose.
A Phase II Study Of Tosedostat (TST) In Combination With Either Cytarabine Or Decitabine In Newly Diagnosed Older Patients With Acute Myeloid Leukemia (AML) Or High-Risk Myelodysplastic Syndrome (MDS)
Authors: Raya Mawad, Pamela S. Becker, Paul C. Hendrie, Bart L Scott, Brent L. Wood, Carol Dean, Ravinder K Sandhu, H. Joachim Deeg, Roland B. Walter, Frederick R. Appelbaum, Lixia Wang, Han Myint, Jack Singer, Elihu H. Estey, John M. Pagel
Journal: Blood (2013)
&lt;italic&gt;Brief Communication:&lt;/italic&gt; Zinc Suppression of Initiation of Sarcoma 180 Growth&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: A D Woster, M L Failla, M W Taylor, E D Weinberg
Journal: JNCI Journal of the National Cancer Institute (1975)

Subcutaneous administration of 80 mug zinc daily to mice that had received an intraperitoneal inoculation of 1 times 10-6 sarcoma 180 cells within the preceding 2 days resulted in protection of up to 60% of the hosts. In animals in which tumors grew, daily injections of zinc did not alter the rate of tumor cell growth. We hypothesized that the metal suppressed initiation of tumor cell reproduction, possibly by stimulation of host defense cell mechanisms.
Retinoblastoma Protein and the Leukemia-Associated PLZF Transcription Factor Interact To Repress Target Gene Promoters.
Authors: Kevin R. Petrie, Fabien Guidez, Jun Zhu, Gareth Owen, Yat Peng Chew, Samuel Waxman, Jonathan D. Licht, Sibylle Mittnacht, Zelent Arthur
Journal: Blood (2007)
Multi-institutional study of allogeneic bone marrow transplantation using myeloablative busulfan (Bu)/fludarabine (Flu) conditioning and short-course, single-agent graft-versus-host disease (GVHD) prophylaxis with high-dose, post-transplantation cyclophosphamide (PTCy).
Authors: Christopher George Kanakry, Paul V. O'Donnell, Marcos J.G. De Lima, Wei Wei, Terry Furlong, Marta Medeot, Richard J. Jones, Peter F. Thall, Borje Andersson, Leo Luznik
Journal: Journal of Clinical Oncology (2013)

7006 Background: The clinical efficacy of 1) myeloablative BuFlu and 2) PTCy as GVHD prophylaxis have been independently shown in multiple single-center studies. Here, we sought to combine these two promising strategies in the context of a multi-institutional clinical trial. Methods: IV Bu was given in pharmacokinetically adjusted doses to achieve a targeted steady-state concentration. PTCy at 50mg/kg on Days +3 and +4 was administered as sole GVHD prophylaxis. Ninety-two patients (median age 49, range 21-65) receiving HLA-matched allografts (49% related and 51% unrelated) were enrolled at three institutions: 42 at Johns Hopkins, 38 at Fred Hutchinson, and 12 at MD Anderson. Diagnoses included 37 patients with de novo AML (40%), 16 with secondary AML (17%), 15 with acute lymphoblastic leukemia (16%), 13 with myelodysplastic syndrome (14%), 5 with chronic myelogenous leukemia (5%), two with chronic myelomonocytic leukemia (2%), three with non-Hodgkin lymphoma (3%), and one with multiple myeloma (1%). Twenty-five patients (27%) were not in remission by morphologic criteria at the time of allogeneic transplantation and an additional 17 patients (18%) had flow cytometric, cytogenetic, or molecular evidence of disease. Results: Five patients (5.4%) had primary graft failure. The cumulative incidences of grades 2-4 and 3-4 acute GVHD were 51% and 16%, respectively, and the cumulative incidence of chronic GVHD was 14%. GVHD was the primary cause of death in two patients, and one patient died of veno-occlusive disease. The 100 day and 1 year non-relapse mortality were 9.8% and 16%, respectively. Relapse occurred in 24% of these high-risk patients. At 1 year, the EFS was 64% and the OS was 72%. For the 50 patients in complete remission without MRD, at 1 year the EFS was 77% and the OS was 78%. Conclusions: This multi-institutional trial confirms the efficacy of high-dose PTCy as single-agent GVHD prophylaxis and demonstrates that it can be safely and effectively combined with the myeloablative BuFlu conditioning regimen. Clinical trial information: NCT00809276.