tbuckley/cabot-search huggingface dataset:
Validation study on the clinical usefulness of the ICG fluorescence method for detecting sentinel lymph node in early-stage breast cancer in comparison with the dye method.
Authors: T. Sugie, T. Sawada, N. Tagaya, T. Kinoshita, K. Yamagami, H. Suwa, K. Yoshimura, M. Sumi, M. Toi
Journal: Journal of Clinical Oncology (2011)

1122 Background: Sentinel lymph node (SLN) biopsy using indocyanine green (ICG) fluorescence method is a technique that utilizes the fluorescing property of ICG reagent that is used in the dye method. Flow of lymph can be confirmed as real time image from outside the body, and this method is the best for intra-operative sentinel lymph node biopsy. To assess the diagnostic performance of SLN biopsy using ICG fluorescence technique, prospective multicenter study was performed compared with blue dye method. Methods: Patients with T1-3 primary breast cancer without lymph node metastasis were assigned in this study. A combination of ICG as a fluorescence emitting source and indigocarmine as a blue dye were injected in the subreolar area and lymphatic flows were traced with PDE camera (a charge coupled device, Hamamatsu Photonics Co, Japan) and a real time image guided surgery enabled to identify the florescence signal of SLN after meticulous dissection. Extracted lymph nodes were examined for the first SLN or the second and further SLNs and classified in terms of ICG fluorescence, blue dye. Primary endpoint in this study is the difference in the number of lymph nodes identified by the fluorescence and the dye method. Secondary endpoints are identification rate, metastatic rate to SLNs and metastatic rate by order of SLNs. Results: Ninety-nine eligible patients were included in this study. The number of lymph nodes identified by fluorescence method was significantly larger than dye method (p<0.001). The SLN identification rate of fluorescence and dye method was 99% and 78%, respectively (p<0.001). Twenty of 99 patients had a positive SLN and ICG fluorescence method identified all these patients. The first SLN identified had both ICG fluorescence and blue dye (77%) or ICG fluorescence alone (23%). Of the 20 patients with lymph node metastasis, 100% was positive in the first SLN. Conclusions: SLN biopsy using ICG fluorescence achieves a high identification rate and is superior to dye method. The first SLN identified by ICG fluorescence method represents the exact axillary status. Direct comparison between ICG fluorescence and radio isotope method is currently on the way.
Do younger women with early breast cancer have a higher recurrence risk?
Authors: K. K. L. Yap, D. N. Efiom-Ekaha
Journal: Journal of Clinical Oncology (2011)

178 Background: There has been conflicting evidence in the literature regarding the association between age and breast cancer recurrence risk. Cancer Research UK reported a better survival among patients aged 50 to 69 compared to younger women. The National Cancer Institute had reported the same, but only in women with stage 1 cancer. Fox Chase Cancer Center and Lyman et al had however suggested that there is no association between breast cancer recurrence and age at diagnosis. Our objective is to investigate the association between breast cancer recurrence and age at diagnosis. Methods: An IRB-exempted restrospective chart review of female patients at Wellspan Group who had Oncotype DX analysis in 2008 and 2009. Data collected included Oncotype DX score and age at diagnosis. Data was analyzed to determine the correlation between Oncotype DX score and age at diagnosis. The patients were divided into three groups: age less than 45 years, age 45 to 59 years, and age 60 or more. Oncotype DX score was used because it has been clinically validated as a reliable predictor of breast cancer recurrence for node-negative breast cancer. Results: A total of 125 patients were identified. The Pearson Correlation score for Oncotype DX score and age at diagnosis was -0.064 (p = 0.478). The mean score was 18.36 for those aged less than 45 years, 22.04 for those aged 45 to 59 years, and 19.16 for those age 60 or more. The difference between these groups was not significant (p = 0.340). Conclusions: There was neither significant correlation between breast recurrence and age, nor difference between the three age groups. Our study shows that age at diagnosis is not an independent predictor of breast cancer recurrence risk.
Doxorubicin (Doxo) and dacarbacin (DTIC) as first-line therapy for patients (pts) with locally advanced or metastatic leiomyosarcoma (LMS) and liposarcoma (LPS).
Authors: U. Bitz, D. Pink, C. Busemann, P. Reichardt
Journal: Journal of Clinical Oncology (2011)

10094 Background: Prognosis of patients with metastatic soft tissue sarcoma (mSTS) remains poor with an overall survival of 12 months after first diagnose of metastases. Monotherapy with doxo is still considered standard treatment in mSTS. Combination therapy results in higher response rates but did not yet demonstrate a benefit in overall survival in first-line treatment. Methods: We performed a retrospective analysis of 44 pts with locally advanced or metastatic LMS (22 pts) and LPS (22 pts) who had been treated with doxo (75 mg/m2 day 1) and DTIC (400 mg/m2 days 1-3) as first-line therapy. Response to treatment was evaluated every three cycles with CT using RECIST criteria. Median progression free survival (mPFS) and median overall survival (mOS) since time of first diagnosis, first diagnosis of metastases and since starting treatment with doxo and DTIC was calculated. Results: Best response to treatment in LMS was PR in 57% of pts, and SD in 43%. In LPS 5% of pts achieved CR, 35% PR, 50% SD and 10% PD, respectively. mPFS in patients with LPS and LMS was 14 months and 9 months, respectively. In pts with LPS, median follow-up was 57 months since start of chemotherapy, 29 months since first diagnosis of metastasis and 101 months since first diagnose of disease. In pts with LMS median follow-up since start of chemotherapy was 27 months, 28 months since first-diagnose of metastases and 30 months since first diagnose of disease. Median OS was not reached in both groups. Therapy was well tolerated, dose reduction was necessary in 27% of pts due to haematotoxicity grade 3 or 4. Conclusions: First line-chemotherapy with doxo and DTIC is an effective treatment option in locally advanced or metastastic LMS and LPS. Our results compare favourably to other published first-line data in these sarcoma subgroups.
Phase I dose-escalation trial of tremelimumab in combination with bicalutamide in patients with recurrent prostate cancer.
Authors: J. M. Lang, M. J. Staab, G. Liu, G. Wilding, D. G. McNeel
Journal: Journal of Clinical Oncology (2011)

174 Background: Antibodies targeting CTLA-4 have demonstrated anti-tumor efficacy in human clinical trials. The mechanism of this effect is presumably in part mediated by the expansion of tumor-specific T cells. Androgen deprivation (AD), the cornerstone of treatment for patients with metastatic prostate cancer, has been demonstrated to cause prostate tissue apoptosis and lymphocytic inflammation. We hypothesized that treatment with AD, followed by an anti-CTLA-4 antibody, could have benefit by augmenting a tumor-specific immune response elicited with AD. We report the initial results from the dose-escalation portion of a phase I trial evaluating tremelimumab in combination with high-dose bicalutamide. Methods: Eligible patients were those with clinical stage D0 prostate cancer (rising serum PSA but no evidence of metastatic disease). Subjects were treated in two courses, 3 months apart, in which they received bicalutamide 150 mg daily for 28 days and tremelimumab on day 29. Patients were treated in cohorts of six, defined by tremelimumab dose (3 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg). The primary endpoint of the trial was safety. Secondary endpoints included measures of PSA kinetics and identification of a maximum tolerated dose (MTD). Results: Eleven patients were enrolled and completed the dose-escalation portion of the trial and at least one year of follow up. Dose-limiting toxicities (DLTs) were observed in 2/5 subjects treated at 6 mg/kg, and included grade 3 diarrhea and a grade 3 skin rash. One of six subjects treated at 3 mg/kg tremelimumab required hospitalization for colitis. No other grade 3 or grade 4 events were observed. Common grade 1/2 events included fatigue, hot flashes, diarrhea, abdominal discomfort, rash, pruritis, and gynecomastia. Two patients experienced a prolongation in PSA doubling time detectable months after completing treatment. Conclusions: Tremelimumab, administered at 3 mg/kg every 3 months in combination with AD, was found to be the MTD and with reasonable safety in this population. The identification of patients with prolonged stable disease following treatment suggests that future studies could explore repetitive administration of this combination. [Table: see text]
Immune-related alopecia (areata and universalis) in cancer patients receiving immune checkpoint inhibitors
Authors: A. Zarbo, V.R. Belum, V. Sibaud, S. Oudard, M.A. Postow, J.J. Hsieh, R.J. Motzer, K.J. Busam, M.E. Lacouture
Journal: British Journal of Dermatology (2016)

Cytotoxic T-lymphocyte-associated protein-4, programmed cell death protein and programmed cell death protein ligand 1 monoclonal antibodies (immune checkpoint inhibitors), are used to treat various malignancies. Their mechanism of action involves the inhibition of negative regulators of immune activation, resulting in immune-related adverse events (irAEs) including endocrinopathies, pneumonitis, colitis, hepatitis and dermatological events. Dermatological irAEs include maculopapular rash, pruritus, vitiligo, blistering disorders, mucocutaneous lichenoid eruptions, rosacea and the exacerbation of psoriasis. Alopecia secondary to immune checkpoint inhibitors has been reported in 1·0-2·0% of treated patients. Our objective is to characterize for the first time the clinicopathology of patients with alopecia areata (AA) secondary to immune checkpoint inhibitors, including the first report of anti-PD-L1 therapy-induced AA, and review of the literature. Four cases of patients who developed partial or complete alopecia during treatment with immune checkpoint inhibitors for underlying cancer were identified from our clinics. Methods include the review of the history and clinicopathologic features. Three patients (75%) had AA and one had universalis. Two patients had a resolution after topical, oral or intralesional therapies and one had a resolution after immunotherapy was discontinued; all regrown hair exhibited poliosis. One of the four patients had coincident onychodystrophy. This report describes a series of four patients who developed partial or complete alopecia (i.e. areata and universalis) during treatment with immune checkpoint inhibitor therapies for cancer. The recognition and management of hair-related irAEs are important for pretherapy counselling and interventions that contribute to maintaining optimal health-related quality of life in patients.
Early Lung Disease in Infants and Preschool Children with Cystic Fibrosis. What Have We Learned and What Should We Do about It?
Authors: Sarath C. Ranganathan, Graham L. Hall, Peter D. Sly, Stephen M. Stick, Tonia A. Douglas
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

The past decade has seen significant advances in understanding of the pathogenesis and progression of lung disease in cystic fibrosis (CF). Pulmonary inflammation, infection, and structural lung damage manifest very early in life and are prevalent among preschool children and infants, often in the absence of symptoms or signs. Early childhood represents a pivotal period amenable to intervention strategies that could delay or prevent the onset of lung damage and alter the longer-term clinical trajectory for individuals with CF. This review summarizes what we have learned about early lung disease in children with CF and discusses the implications for future clinical practice and research.
Detection of prostate cancer with HistoScanning.
Authors: R. Epplen, T. van Erps, D. Thueer, R. Knuechel-Clarke, A. Heidenreich
Journal: Journal of Clinical Oncology (2011)

55 Background: HistoScan is a tool for differentiation, visualization and quantification of changes in solid organ tissue. It is used in combination with transrectal ultrasound that transmits data to a computer program. Data is processed and suspicious areas shown. Our objective was to compare HistoScan with histopathology of radical prostate specimens and to determine sensitivity in detection regarding cancer volume and localization. Methods: 52 patients who underwent radical prostatectomy HistoScan was performed one day preoperatively. Scan with the largest suspicious volume was used for evaluation. All prostatectomy specimens were processed according to the Stanford protocol. The prostate specimens were divided into a grid of 9 different areas. HistoScan findings were correlated with final pathology regarding localization and volume. A match was defined as well a positive lesion in HistoScan as in a correspondent histopathologically proven area. Results were analyzed regarding to T-stadium, Gleason Score (GS), PSA, tumor volume and volume of HistoScan lesions. Results: Mean patient age was 63.6 years, mean PSA was 8.97 ng/ml, mean prostate volume was 45.4 ml and mean tumor volume was 4.1 ml. 27 patients (pts) had a pT2 tumour, 25 pT3 carcinoma. 4 pts had salvage prostatectomy. 6 pts had a final GS, 34 and 8 pts had GS 7 and GS ≥8 respectively. Sensitivitiy was 75% for detecting prostate cancer. 64% of the cases showed a good correlation for tumor volume. Results were identical for normal and salvage prostatectomy. Sensitivity was higher for T3 tumors than for pT2 tumors. HistoScan detected 50% of the GS 6 tumors, 74% of GS 7 and 100% of GS ≥8. HistoScan detected small tumors (&lt;1 ml) in 60%, intermediate tumours (1-5 ml) and large tumours (&gt;5 ml) in 87 and 82% respectively. Similar findings are seen regarding the volume of suspicious lesions in HistoScan. For small (≤ 0.5 ml), intermediate (0.5-2 ml) and large (&gt;2ml) lesions, HistoScan correctly predicted localisation in 53%, 86% and 85% respectively. Conclusions: HistoScan has a great potential in detection of significant prostate cancer. In particular extracapsular poor differentiated and large tumors show a high detection rate. However, larger prospective studies are needed to verify these preliminary results. No significant financial relationships to disclose.
Impact of Non High-Risk Chromosomal Abnormalities on the Outcome of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma
Authors: Sairah Ahmed, Heather Lin, Veera Baladandayuthapani, Mubeen A Khan, Gary Lu, Gabriela Rondon, Sofia Qureshi, Yvonne T Dinh, Qaiser Bashir, Nina Shah, Simrit Parmar, Chitra M Hosing, Uday Popat, Sergio A Giralt, Robert Z. Orlowski, Jatin J Shah, Richard Champlin, Muzaffar H. Qazilbash
Journal: Blood (2011)
Characterization of MDX-1401, a Human Anti-CD30 Antibody with Enhanced Effector Function, for Therapy of Malignant Lymphoma.
Authors: Pina M. Cardarelli, Cristina Loomis, Ben Preston, Amelia Black, David Passmore, Tseng-Hui Chen, Sharline Chen, Jie Liu, Michelle R Kuhne, Mohan Srinivasan, Albert Assad, Alison Witte, Marco Coccia, Robert F. Graziano, David J. King
Journal: Blood (2008)
Reduced Oxidative Stress and Enhanced Nitric Oxide (NO) Bioavailability in Transgenic-Knockout Sickle Mice Expressing Fetal Hemoglobin (HbF) Is Mediated by Decreased Sickling and Hemolysis.
Authors: Trisha Dasgupta, Mary E. Fabry, Dhananjay K. Kaul
Journal: Blood (2007)
Mechanism of early radiographic response to imatinib in GIST.
Authors: J. Gao, J. C. McAuliffe, A. J. F. Lazar, W. Wang, H. Choi, K. Hunt, D. M. Araujo, R. E. Pollock, R. S. Benjamin, J. C. Trent
Journal: Journal of Clinical Oncology (2011)

10049 Background: Most gastrointestinal stromal tumors (GISTs) harbor activating mutations of the receptor tyrosine kinase KIT, which is inhibited by imatinib (Novartis, Switzerland). Treatment response of GISTs to imatinib is characterized by decreased contrast uptake or tumor size on computed tomographic (CT) imaging. We sought to elucidate the mechanism by which imatinib decreases contrast enhancement of GISTs during the first 3-7 days of therapy. Methods: As part of an IRB-approved, phase II, prospective, randomized clinical trial of preoperative imatinib for GIST patients, radiographic data from 13 patients pre-/post-imatinib treatment were assessed for tumor blood flow (TBF), perfusion and transit time by perfusion CT and tumor response by positron-emission tomography (PET). Tissue specimens pre-/post-imatinib treatment were analyzed for blood vessel density (TBVD)/caliber, stem cell factor (SCF, KIT ligand) expression, KIT phosphorylation and tumor endothelial cell (TEC) apoptosis. GIST and endothelial cell lines (MVEC/HuVEC) were used to assess whether imatinib influences endothelial cell survival through the SCF/KIT signaling pathway. Results: 7 of 13 patients with PET response to imatinib demonstrated a mean 45% decrease (p=0.02) in TBF, whereas 6/13 non-responders had a mean 19% increase of TBF (p=0.21) by perfusion CT. TBVD/caliber wasn’t affected by imatinib in either group as assessed by immunofluourescence. Imatinib treatment resulted in a 14% increase in TEC apoptosis (p=0.015), compared to only 3% in the non-responders (p=0.52) by immunofluourescent TUNEL assay. Additionally, imatinib significantly blocked KIT phosphorylation of the TECs in imatinib responders but not in non-responders by immunoflourescence. In vitro, imatinib suppressed SCF expression from GIST cells, inhibited SCF-induced KIT phosphorylation by western blot and promoted apoptosis as manifested by increased caspase 3 activation in MVEC. Conclusions: The radiographic response of GISTs to imatinib correlates with decreased TBF, TEC apoptosis and SCF/KIT signaling inhibition of MVEC. These findings provide the first mechanistic support of our recently proposed criteria for evaluation of GIST response to imatinib (Choi et al, JCO 2007, 25:1760).
“Don't Eat me”: CD47 and LFA-1 Modulate CLL Response to Nurselike Cells-Mediated Antibody-Dependent Phagocytosis Induced by Rituximab and Obinutuzumab (GA101)
Authors: Loic Ysebaert, Emilie Laprevotte, Christian Klein, Guy Laurent, Anne Quillet-Mary, Mary Poupot, Jean-Jacques Fournié
Journal: Blood (2011)
Insights on consciousness from taste memory research
Authors: Milagros Gallo
Journal: Behavioral and Brain Sciences (2016)

Abstract Taste research in rodents supports the relevance of memory in order to determine the content of consciousness by modifying both taste perception and later action. Associated with this issue is the fact that taste and visual modalities share anatomical circuits traditionally related to conscious memory. This challenges the view of taste memory as a type of non-declarative unconscious memory.
Use of genetic variants of LMTK3 to predict tumor recurrence in female localized gastric adenocarcinoma.
Authors: Takeru Wakatsuki, Pierre Oliver Bohanes, Wu Zhang, Armin Gerger, Dongyun Yang, Yan Ning, Thomas Winder, Melissa Janae Labonte, Peter M.D. Wilson, Leonor Benhaim, Rita El-Khoueiry, Anthony B. El-Khoueiry, Syma Iqbal, Georgios Giamas, Justin Stebbing, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2012)

63 Background: Previous study suggests that high basal Lemur Tyrosine Kinase 3 (LMTK3) expression was associated with advanced stage of primary breast cancers as well as decreased overall and disease-free survival. LMTK3 was also found overexpressed in gastric cancer. Our previous data showed the mutant variants of two single nucleotide polymorphisms (SNPs) in LMTK3 (rs8108419 and rs9989661) were independently associated with reduced time to tumor recurrence (TTR) in colon cancer (CC). We hypothesized that LMTK3 rs808419 and rs9989661 may predict TTR in a cohort of localized gastric cancer patients. Methods: Either blood or FFPE tissue specimens obtained from 137 localized (stage Ib-IV) GA patients (54 females and 83 males) were included in this study. All patients were treated with surgery alone or surgery and adjuvant (radio)-chemotherapy at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC), the Los Angeles County/University of Southern California Medical Center, or the Memorial Sloan-Kettering Cancer Center from 1992 to 2008. The median follow-up was 3.3 years. LMTK3 rs8108419 and rs9989661 were determined by PCR-RFLP. The primary endpoint of the study was TTR. Results: LMTK3 rs9989661 was significantly associated with TTR in females GA patients. Female patients with minor C allele (TC or CC) (n=25) of LMTK3 rs9989661 showed significantly longer median TTR=7.0 (95%CI: 2.1-8.3+) years compared to those harboring homozygous TT genotype. (n=28), TTR=1.7 (95%CI: 0.7-7.0+) years.( log-rank p=0.025; univariate analysis). After Cox proportional hazards model adjustment for stage and type of adjuvant chemotherapy, this result remained significant (HR: 0.14, 95%CI: 0.02-0.94, multivariate Wald p value = 0.043 in the dominant model). No significant association was found between TTR and LMTK3 rs9989661 in men and rs8108419 in both genders. Conclusions: This pilot study demonstrating LMTK3 rs9989661 may be potential molecular marker to predict TTR in female localized GA. Larger prospective trials are warranted to confirm these findings, and in vitro and in vivo studies are needed to identify the underlying biological mechanism.
Use of intraoperative digital specimen mammography to improve operative efficiency.
Authors: M. Valero, L. S. Dominici, M. Golshan
Journal: Journal of Clinical Oncology (2011)

138 Background: The traditional method of confirming excision of a targeted lesion during wire localized breast biopsy has been with standard specimen mammograms (SSM). More recently, intraoperative digital specimen mammograms (IDSM) have been used to provide immediate specimen evaluation for the surgeon in the operating room. We sought to evaluate operative time with the use of IDSM versus SSM. Methods: A retrospective chart and electronic operating room record review of consecutive patients of a single breast surgical oncologist at a quaternary care academic center. Three hundred and forty-four (344) consecutive patients from 2003 to 2010 who underwent wire localized excisional biopsy or wire localized lumpectomy without lymph node evaluation, with specimen evaluation by IDSM or SSM. Operative time, defined as documented time of incision to documented time of closure, was recorded for SSM versus IDSM. Results: We compared demographics of the two groups transitioning from SSM to IDSM (Table). During the study period, median operative time decreased from 50 minutes in the SSM group to 37 minutes in the IDSM group (p&lt;0.001). Conclusions: Operative times with the use of IDSM are significantly shorter than with SSM. Downstream effects include decreases in anesthetic time, anesthetic use, operating room charges, and increasing surgeon productivity. [Table: see text]