tbuckley/cabot-search huggingface dataset:
Large-cell transformation following detection of minimal residual disease in cutaneous T-cell lymphoma: molecular and in situ analysis of a single neoplastic T-cell clone expressing the identical T-cell receptor.
Authors: J T Wolfe, L Chooback, D T Finn, C Jaworsky, A H Rook, S R Lessin
Journal: Journal of Clinical Oncology (1995)

PURPOSE One of the unique characteristics of cutaneous T-cell lymphoma (CTCL) is its ability to undergo cytologic transformation in which the malignant T cells develop the morphologic appearance of a large-cell lymphoma. Reported to occur in up to 20% of advanced cases, large-cell transformation (LCT) is associated with an aggressive clinical course. Little is known about the risk factors or the molecular mechanisms of LCT. Before current immunohistochemical and molecular techniques, it was not possible to determine if LCT represented changes of the initial neoplastic T-cell clone or, in fact, was a distinct second malignancy. The goal of this study was to define the clonal evolution of LCT in CTCL. PATIENTS AND METHODS Polymerase chain reaction (PCR) amplification of T-cell receptor-beta (TCR-beta) gene rearrangements and immunohistochemistry with monoclonal antibodies to TCR-V beta regions were used as markers of T-cell clonality to analyze the skin and peripheral blood of a patient with CTCL and LCT. RESULTS We first detected the presence of minimal residual disease (MRD) in a CTCL patient with a complete clinical response to biologic response modifiers (BRMs). When clinical relapse occurred and demonstrated LCT, TCR-beta-PCR and in situ immunohistochemistry with a specific TCR-V beta monoclonal antibody identified a single neoplastic T-cell clone that expressed the identical TCR as the original clone. CONCLUSION Our results confirm a common clonal origin for CTCL and LCT. We also provide evidence of MRD in CTCL by molecular analysis, implying that residual malignant cells maintain a potential for clinical relapse and possibly LCT. The role of MRD detection remains to be defined in the clinical assessment of CTCL. LCT in CTCL provides a unique model to investigate the molecular events that underlie terminal-stage tumor progression.
Post-progression therapy (PPT) effect on survival in AVF2107, a phase III trial of bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC)
Authors: E. E. Hedrick, H. Hurwitz, S. Sarkar, S. Griffing, W. Novotny, A. Grothey
Journal: Journal of Clinical Oncology (2004)

3517 Background: Bevacizumab [Avastin (BV)], a recombinant humanized monoclonal antibody against VEGF, significantly prolongs overall survival (OS) when added to 1st-line chemotherapy for mCRC. BV joins 5-Fluorouracil/ leucovorin (5-FU/LV), irinotecan,(I) and oxaliplatin (Ox) as agents with demonstrated survival benefit in the treatment of mCRC. A recent analysis of phase III trials in mCRC, where treatment with 5-FU/LV, I, and Ox was available, demonstrates a correlation between the percentage of patients receiving all 3 active agents and OS (Grothey, J Clin Oncol, in press). We analyzed the effect of use of active agents over the treatment course on OS in AVF2107. Methods: The findings of AVF2107 have been reported. In AVF2107, use and composition of PPT (Ox-containing vs non-Ox-containing) was at the discretion of the investigator. OS was determined in the two randomized treatment arms [IFL/ placebo (Arm 1, n=412) and IFL/ BV (Arm 2, n=402)] according to PPT use and composition. Baseline characteristics were compared between these subgroups. Results: 231 (56.2%) and 222 (55.2%) patients received PPT in Arms 1 and 2, respectively. Table 1 summarizes OS by PPT composition. For Arm 1 patients who received PPT, the group receiving Ox PPT was younger (median age 57 vs 64 yrs), had better performance status (ECOG 0, 64 vs 52%) and a longer 1st-line PFS (7.4 vs 5.8 months) compared to those receiving non-Ox PPT. For Arm 2, differences between Ox and non-Ox PPT subgroups were not observed. Conclusion: BV prolongs survival in patients with mCRC when added to first-line chemotherapy. In addition, this subset analysis suggests that a treatment strategy incorporating all active agents over the course of disease optimizes OS. These results are consistent with an analysis of other recent phase III trials in mCRC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Inc. Eli Lilly & Co.; Genentech, Inc.
Chemotherapy-related serious adverse events and health care expenditures among commercially insured women with breast cancer
Authors: M. J. Hassett, J. Pakes, A. J. O’Malley, J. P. Newhouse, C. C. Earle
Journal: Journal of Clinical Oncology (2005)

6000 Background: The number, nature, and costs of serious adverse events experienced by women receiving chemotherapy for breast cancer outside of clinical trials are unknown. Methods: From a database of medical claims for individuals with employer-provided health insurance made January 1998 - December 2000, we identified women </= 63 years old with newly diagnosed breast cancer. Medical and pharmacy claims were examined during the 6 months after cancer diagnosis. ICD-9, DRG, and CPT codes for chemotherapy-related & unrelated adverse events were identified. Total ER visits, total inpatient admissions, admissions or ER visits for adverse events (AEs), and health care expenditures were assessed for those receiving chemotherapy. Those not receiving chemotherapy served as a control group. Results: Of 8,749 women with breast cancer, 2,352 (27%) received chemotherapy. Approximately 51% of chemotherapy recipients visited the ER or were admitted at least once within 6 months of diagnosis, compared to 23% of women not receiving chemotherapy (adjusted OR 3.36). Once admitted, chemotherapy recipients spent twice as long in the hospital (median 9.8 vs. 4.6 days). Chemotherapy-related AEs were more common among chemotherapy recipients (OR for infections 3.23; neutropenia or thrombocytopenia 12.45; anemia 2.91; nausea, emesis or diarrhea 3.44; malnutrition 3.07; & dehydration 4.11) whereas chemotherapy-unrelated AEs were not (hip fractures, MIs, etc.), after adjusting for age, co-morbidities, metastatic status, and other factors. Mean per patient expenditures for the 6-month observation period were greater among chemotherapy recipients than non-recipients ($432 vs. $186 for co-payments; $7,468 vs. $4,446 for ER visits; $20,774 vs. $11,946 for admissions). Conclusions: Chemotherapy for breast cancer is associated with frequent AEs in younger, commercially insured women with breast cancer. These events result in more emergency room visits & hospitalization, longer duration admissions, and higher health care costs for payers and patients. Serious chemotherapy-related AEs appear to be more common and more costly than predicted by large clinical trials. No significant financial relationships to disclose.
Impaired microbial killing by neutrophils from patients with protein kinase C delta deficiency
Authors: Katka Szilagyi, Roel P. Gazendam, John L. van Hamme, Anton T.J. Tool, Michel van Houdt, Wilhelm A.J.W. Vos, Paul Verkuijlen, Hans Janssen, Alexandre Belot, Laurent Juillard, Elisabeth Förster-Waldl, Kaan Boztug, Georg Kraal, Menno P.J. de Winther, Taco W. Kuijpers, Timo K. van den Berg
Journal: Journal of Allergy and Clinical Immunology (2015)
Sonodynamic and photodynamic therapy in advanced refractory breast cancer.
Authors: Xiaohuai Wang, Lucy Qing Li, Weimin Zhang, Yifan Luo, Douglas Graham Mitchell
Journal: Journal of Clinical Oncology (2012)

118 Background: Sonodynamic therapy (SDT), a procedure related with photodynamic therapy, is a promising new modality for treating deep-seated cancer. Two new chlorophyll derived sono-photo-sensitizing agents, along with equipment for systemic SDT, have been developed by EEC Biotech and all approved by regulator for safety on human. Animal studies demonstrate that the sensitizers are specifically absorbed into tumor cells and SDT does inhibit growth of mouse S-180 sarcoma. An in vitro experiment with human breast cancer cell-line showed that SDT was strongly synergetic with chemotherapy. Using sono-photo-dynamic therapy (SPDT) as a supplementary or salvage treatment, we have got some positive results in advanced refractory breast cancers. Methods: Twelve patients were pathologically proven advanced breast carcinoma. Eleven had metastases in viscera including brain, and nine in bones. Ten had chemotherapy before, nine failed at least second lines of conventional chemotherapy. With SPDT, Patients took the sensitizers sublingually on days 1 and 2, red light and multiple ultrasound transducers irradiate tumor area and whole body on days 4 to 6. The treatment was repeated. Nine patients had concurrent chemo with range from moderate to ¼ conventional dosages selected to keep side effects at grade II or better. Results: The twelve patients achieved CR 3(25%), PR 6 (50%), MR 1, SD 2, with an overall response rate of 75%.Median overall survival exceeded 14.5 months. SPDT as sole therapy was effective in three cases. Four treated repeatly with SPDT also achieved positive result after tumor relapsed. One patient with brain metastases showed much reduced. The two SD were TNBC with inflammation-like metastases on the chest surface. The main SPDT side effects were easily reversible mild pain in tumor areas, tiredness and weakness.There was no skin sensitivity.SPDT/dose controlled chemo was well tolerated, even a terminally ill patient was treated safely and effectively. Conclusions: These preliminary data suggest that SPDT has almost no toxicity, and may dramatically enhance chemo efficacy in some refractory advanced breast cancer cases. SPDT has a good trend to be a new systemic, low toxicity tumor therapy and merit for further investigation.
Hormone Receptors in Breast Cancer and Response to Chemotherapy
Authors: M E Lippman, J C Allegra
Journal: New England Journal of Medicine (1979)

Other data reveal the important prognostic value of estrogen-receptor determinations in identifying patients at greater risk of relapse. The data of Drs. Legha et al. do not allow any conclusions on the effect of receptor status, as assessed (indirectly) by previous hormone responsiveness on response to chemotherapy. Dr. Panko has identified important potential problems with the study of Kiang et al. There is no question that some estrogen-receptor tumors can on substquent biopsies be estrogen-receptor positive; chemotherapy may enhance this selection of cells.
Pilot study of intratumoral (IT) cryoablation (cryo) in combination with systemic checkpoint blockade in patients with metastatic melanoma (MM)
Authors: Dae Won Kim, Cara Haymaker, Natalie McQuail, Elizabeth Sirmans, Christine Spencer, Isabella Glitza, Rodabe Amaria, Scott Woodman, Sapna Patel, Michael Davies, Cassian Yee, Wen-Jen Hwu, Chantale Bernatchez, Jennifer Wargo, Padmanee Sharma, James Allison, Patrick Hwu, Alda Tam, Adi Diab
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Cryo is an effective modality for pain palliation and local control of soft tissue and bone metastases. Cryo induces necrotic cell death, and combination cryo with anti-CTLA-4 generates potent systemic anti-tumor immune responses in preclinical models and small clinical studies.
MALIGNANT SKIN LESIONS
Authors: Elke C. Bornhövd, Monika-H. Schmid-Wendtner, Matthias Volkenandt, Clemens-M. Wendtner, Christian A. Sander
Journal: Journal of Clinical Oncology (1999)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.12.3853 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10577859 MALIGNANT SKIN LESIONS Elke C. BornhövdxElke C. BornhövdSearch for articles by this author , Monika-H. Schmid-WendtnerxMonika-H. Schmid-WendtnerSearch for articles by this author , Matthias VolkenandtxMatthias VolkenandtSearch for articles by this author , Clemens-M. WendtnerxClemens-M. WendtnerSearch for articles by this author , Christian A. SanderxChristian A. SanderSearch for articles by this author Show More University of Munich, LMU Munich, Germany https://doi.org/10.1200/JCO.1999.17.12.3853 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Genomic Data from Extinct North American<i>Camelops</i>Revise Camel Evolutionary History
Authors: Peter D. Heintzman, Grant D. Zazula, James A. Cahill, Alberto V. Reyes, Ross D.E. MacPhee, Beth Shapiro
Journal: Molecular Biology and Evolution (2015)

Recent advances in paleogenomic technologies have enabled an increasingly detailed understanding of the evolutionary relationships of now-extinct mammalian taxa. However, a number of enigmatic Quaternary species have never been characterized with molecular data, often because available fossils are rare or are found in environments that are not optimal for DNA preservation. Here, we analyze paleogenomic data extracted from bones attributed to the late Pleistocene western camel, Camelops cf. hesternus, a species that was distributed across central and western North America until its extinction approximately 13,000 years ago. Despite a modal sequence length of only around 35 base pairs, we reconstructed high-coverage complete mitochondrial genomes and low-coverage partial nuclear genomes for each specimen. We find that Camelops is sister to African and Asian bactrian and dromedary camels, to the exclusion of South American camelids (llamas, guanacos, alpacas, and vicuñas). These results contradict previous morphology-based phylogenetic models for Camelops, which suggest instead a closer relationship between Camelops and the South American camelids. The molecular data imply a Late Miocene divergence of the Camelops clade from lineages that separately gave rise to the extant camels of Eurasia. Our results demonstrate the increasing capacity of modern paleogenomic methods to resolve evolutionary relationships among distantly related lineages.
Pharmacology of the Respiratory Tract
Journal: Thorax (1994)

Measurement of distal airspace sizeAirspace size in human lungs obviously depends on the degree to which the lung is inflated and on tissue shrinkage in prep- aration for histological examination.Dr D Lamb et al (October 1993;48:1012-7) minimise the latter by embedding tissue in methacrylate but appear to ignore the for- mer.They inflated the resected lungs used in their study with 10% buffered formalin at a transpulmonary pressure of 25 cm H2O for a minimum of 24 hours.What technique did they use and how well were the lungs in- flated?Satisfactory inflation via the bronchus of surgically resected lobes has been found unsatisfactory in two Vancouver hospitals.In one, expansion had to be achieved by inflation with fixative through the pleura using a large bore needle.'In another,2 using a technique similar to that of Lamb et al, the mean ratio of predicted lobar volume to fixed lobar volume was 3 50.More to the point, the standard deviation of this ratio was 2 03 indicating huge potential errors.How did Lamb et al correct for these when measuring airspace size (AWUV)?
Pegylation of High-Density Lipoprotein Decreases Plasma Clearance and Enhances Antiatherogenic Activity
Authors: Andrew J. Murphy, Samuel Funt, Darren Gorman, Alan R. Tall, Nan Wang
Journal: Circulation Research (2013)

Rationale: Infusions of apolipoprotein AI (apoAI), mimetic peptides, or high-density lipoprotein (HDL) remain a promising approach for the treatment of atherosclerotic coronary disease. However, rapid clearance leads to a requirement for repeated administration of large amounts of material and limits effective plasma concentrations. Objective: Because pegylation of purified proteins is commonly used as a method to increase their half-life in the circulation, we determined whether pegylation of apoAI or HDL would increase its plasma half-life and in turn its antiatherogenic potential. Methods and Results: Initial pegylation attempts using lipid-poor apoAI showed a marked tendency to form multi-pegylated (PEG) species with reduced ability to promote cholesterol efflux from macrophage foam cells. However, pegylation of human holo-HDL or reconstituted phospholipid/apoAI particles (rHDL) led to selective N-terminal monopegylation of apoAI with full preservation of cholesterol efflux activity. The plasma clearance of PEG-rHDL was estimated after injection into hypercholesterolemic Apoe –/– mice; the half-life of pegylated PEG-apoAI after injection of PEG-rHDL was increased ≈7-fold compared with apoAI in nonpegylated rHDL. In comparison with nonpegylated rHDL, infusion of PEG-rHDL (40 mg/kg) into hypercholesterolemic Apoe –/– mice led to more pronounced suppression of bone marrow myeloid progenitor cell proliferation and monocytosis, as well as reduced atherosclerosis and a stable plaque phenotype. Conclusions: We describe a novel method for effective monopegylation of apoAI in HDL particles, in which lipid binding seems to protect against pegylation of key functional residues. Pegylation of apoAI in rHDL markedly increases its plasma half-life and enhances antiatherogenic properties in vivo.
Interstitial lung disease: time to rethink the snapshot diagnosis?
Authors: Danielle Antin-Ozerkis, Martin Kolb
Journal: Thorax (2015)

An accurate and early diagnosis of idiopathic pulmonary fibrosis (IPF) is critically required for patients and care providers because it dictates very specific management decisions that include referral to transplant, access to new approved drugs, avoidance of immunosuppression and potential referral to palliative care.1 While the original diagnosis of IPF was highly dependent on patterns observed on histology, in 2002 the American Thoracic Society (ATS)/European Respiratory Society (ERS) guideline altered the approach to diagnosis so as to include a clinical–radiological–pathological multidisciplinary diagnosis.2 A careful history, searching for subtle evidence of connective tissue disease, exposures and other known causes for interstitial lung disease (ILD), was emphasised. A radiographic pattern of usual interstitial pneumonia (UIP) on high-resolution CT (HRCT) was described, characterised by basal-predominant fibrosis with peripheral reticular markings, traction airway change, architectural distortion and honeycombing.

With this new classification system, it was proposed, characteristic HRCT findings could lead to a confident diagnosis of IPF without the need for a biopsy. The advantage of using HRCT patterns as a surrogate for pathological findings was particularly appealing given data describing increased risk for acute exacerbation and death following lung biopsy.3 Support for such an approach was increased by studies demonstrating agreement between radiographic and pathological findings. Raghu et al 4 found that the specificity of HRCT for UIP was 90%. Flaherty et al 5 found that the HRCT interpretation of definite UIP in biopsy-proven UIP and non-specific interstitial pneumonia (NSIP) had 100% specificity. Hunninghake et al 6 found that in a blinded prospective evaluation of patients with surgical lung biopsies, a confident HRCT diagnosis of UIP was 95% specific for the pathological finding of UIP. HRCT appearance was also predictive of survival: a definite UIP pattern on HRCT (having all the features described above) was associated with a lower survival …
Unreliable Conclusions of Breast Cancer Screening, Incidence, and Mortality—Reply
Authors: Charles Harding, Francesco Pompei, Richard Wilson
Journal: JAMA Internal Medicine (2016)

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Role of HER2 in the activation of c-Abl in breast cancer cells.
Authors: Y. Chavarri Guerra, J. Esparza López, D. Green, H. Medina-Franco, M. D. Ibarra Sánchez, E. Leon Rodriguez, A. Zentella Dehesa
Journal: Journal of Clinical Oncology (2010)

e21096 Background: HER2/neu, a member of the epidermal growth factor receptor (EGFR) family, is over expressed in approximately 25-30% of breast cancer tumors. HER2-positive breast cancer subtype has been associated with a more aggressive phenotype, but the precise molecular mechanisms that link HER2 over-expression to breast carcinogenesis remain poorly understood. Increase activity of c-Abl, a cytoplasmic kinase of tyrosine residues linked to motility, has been associated with a more aggressive breast cancer phenotype. Methods: In this study we evaluated the possible participation of c-Abl in the HER2/neu signaling pathway. Results: Our results showed that the total amount of c-Abl differs among the three HER2-positive breast cancer cell lines analyzed (T47D, ZR-75-30 and MBCD5). This different level of expression of c-Abl might be related with a more aggressive tumor phenotype. We demonstrated for the first time that in vitro addition of trastuzumab to breast cancer cell lines reduces the level of phosphorylation of the tyrosine-245 residue of c-Abl in all three cancer cell lines. This result strongly indicates that the phosphorylation of c-Abl on Tyr245, an event linked to c-Abl activation, depends on the activity of HER2. The combined use of imatinib (an inhibitor of c-Abl) with trastuzumab had no synergistic effect on the generalized reduction in tyrosine residue phosphorylation, under these conditions only the effect of imatinib dominated. In addition, treatment with trastuzumab decreased cell proliferation in a magnitude that correlated with the level of HER2-overexpression. Conclusions: Taken together, these results strongly support the idea that c-Abl is downstream of the HER2-signaling pathway. These results can contribute to a better understanding of the process of breast carcinogenesis and aid in the design of new therapeutic strategies against this tumor. No significant financial relationships to disclose.
Thermally reduced graphene is a permissive material for neurons and astrocytes and de novo neurogenesis in the adult olfactory bulb in vivo
Authors: Çağla Defteralı, Raquel Verdejo, Laura Peponi, Eduardo D. Martín, Ricardo Martínez-Murillo, Miguel Ángel López-Manchado, Carlos Vicario-Abejón
Journal: Biomaterials (2015)