tbuckley/cabot-search huggingface dataset:
Ultrastaging of sentinel lymph nodes (SLNs) compared to non-SLNs in colorectal (CRca) cancer: Do we need both?
Authors: D. Wiese, S. Saha, M. Ghanem, B. Yestrepsky, M. Patel, N. Bassily, P. Ng, W. Liu, E. Quiachon, J. Badin
Journal: Journal of Clinical Oncology (2007)

4055 Background: SLN mapping (M) accurately stages many solid tumors including CRca. SLNs are 3–5 times more likely to have metastases (mets) when ultrastaged by microsections and IHC as compared to non-SLNs examined by standard pathological methods. It is unknown whether ultrastaging of initially -ve non-SLNs would lead to higher incidence of +ve nodes. Hence, we retrospectively analyzed all initially -ve non-SLNs by microsections and IHC similar to SLNs in CRca patients (pts) undergoing SLNM to determine its impact on final nodal staging. Methods: All CRca pts underwent SLNM by circumferential subserosal injection of 1% lymphazurin. First 1–4 blue nodes were marked as SLNs and ultrastaged by 4 section with H&amp;E and 1 with IHC. All non-SLNs were initially examined by single H&amp; E section and initial staging was made as per AJCC criteria. We re-examined all initially -ve non-SLNs similar to the SLNs by a senior pathologist blinded to prior results. Results: There were 156 pts with Cca and 44 pts with Rca. SLNM was successful in 100% pts with 94% accuracy rate. A total of 2,755 nodes (13.78/pt) were identified, of which 494 were SLNs and 2,261 were non-SLNs. Nodal positivity was 46% and 16% for Cca and Rca pts respectively. Mets were detected in 20.9% of SLNs vs. 8.6% of non-SLNs (p&lt; 0.0001). The exclusive site of nodal mets was detected in 6.5% of SLNs vs.0.8% of non-SLNs (p&lt; 0.0001). Skip mets were found in 6% of pts. After ultrastaging all initially -ve non-SLNs (n=2,065), only 0.58% (12/2065) nonSLNs became +ve in 12 pts. Of these, 10 pts already had +ve SLNs, hence no change of staging occurred. Only 2/200 pts (1%) with initially -ve non-SLNs were found to have a cluster of tumor cells. Thus, ultrastaging of 2065 initially -ve non-SLNs in 200 pts changed the staging from II to III only in 1% of pts. Conclusions: SLNM is highly accurate in staging CRca. The chance of finding additional mets by ultrastaging of all non-SLNs is extremely low (&lt; 1%), hence of little benefit. Therefore, ultrastaging restricted to SLNs alone will assure accurate staging of CRca. [Table: see text] No significant financial relationships to disclose.
Abstract 15604: Combinatorial Treatment with HDAC6 and DNA Methylation Modifiers in Attenuating Lung Vascular Hyperpermeability in LPS-induced Inflammatory Lung Injury
Authors: Johnson Rajasingh, Jayakumar Thangavel, Sheeja Rajasingh, Bahar Barani, Buddhadeb Dawn
Journal: Circulation (2014)

Introduction:  The pathogenesis of acute lung injury (ALI) is characterized by progressive respiratory failure with bilateral alveolar infiltrates and lung edema due to severe disruption of the lung vascular endothelial barrier. No effective therapy is currently available for prevention and treatment of this condition that is often fatal. No study has examined the efficacy of DNA methyl transferase inhibitor (5-Aza 2-deoxycytidine-Aza) and a specific histone deacetylase6 (HDAC6) inhibitor (Tubastatin A, BioVision, CA) combination (referred to as Aza+HDAC6) on inflammation, apoptosis and endothelial barrier function during sepsis.   Hypothesis:  Combinatorial treatment with Aza+HDAC6 would preserve lung microvascular endothelial barrier function and prevent protein-rich tissue fluid accumulation during sepsis.   Methods and Results:  The trans-endothelial electrical resistance (TER) and capillary filtration coefficient (K fc ) data show that in LPS-exposed endothelial cells and mice, therapy with Aza+HDAC6 leads to a significant decrease in lung microvascular permeability as compared with either alone. In an ALI mouse model, post-injury treatment with a single dose of Aza+HDAC6 prevented lung injury and afforded a significantly higher survival rate (80%) as compared with mice treated with either Aza or HDAC6 alone. These effects were mediated by a significant attenuation of adverse lung histopathological changes and preservation of endothelial barrier integrity. Aza+HDAC6 also significantly reduced the lung myeloperoxidase content (MPO) and neutrophil infiltration in the ALI model. The protection was ascribed to the activation of Bcl2-STAT3 signaling pathway and enhanced acetylation of histone markers on the CD31 promoter.   Conclusions:  These data for the first time show the efficacy of Aza+HDAC6 therapy in preventing ALI in LPS-induced endotoxemia, and suggest an essential role of DNMT and HDAC6 in pathogenesis of ALI. This novel combinatorial regimen may improve and prolong the lives of patients with ALI associated with sepsis.
Patients with secondary myelodysplastic syndromes (MDS) who are enrolled in AVIDA, a longitudinal registry for patients receiving azacitidine (AZA)
Authors: D. L. Grinblatt, M. Narang, J. M. Malone, D. A. Sweet, T. S. Dunne, K. A. Sullivan
Journal: Journal of Clinical Oncology (2009)

7094 Background: Prevalence of secondary MDS (sMDS) is increasing because of improved survival of patients treated with chemotherapy or radiotherapy and aging of the population. Methylation of cell cycle regulators is common in sMDS, thus the hypomethylating agent AZA may have a role in the treatment of these patients. AVIDA is a longitudinal, multicenter patient registry designed to prospectively collect data from community-based hematology clinics on the natural history and management of patients receiving AZA. AVIDA patients with sMDS were investigated and compared with registry patients with primary MDS (pMDS). Methods: Baseline demographics and disease characteristics were obtained at enrollment. Transfusion requirements and onset of transfusion independence were recorded. Transfusion independence was defined as no transfusions for at least 56 days. The first day of the 56-day period with no transfusions was noted as the time at which patients first achieved transfusion independence. Results: As of October 8, 2008, 23 patients with sMDS due to exposure to radioiodine (18), benzene (2), radiation (1), or other (2) have received AZA. Median time since diagnosis was 1 month versus 4 months for pMDS patients (n = 203). At baseline, patients with sMDS had a similar median age (71 yrs) compared with pMDS patients (75 yrs). However, a higher proportion of patients with sMDS had a poor-risk karyotype (44% vs. 11%), 2 to 3 cytopenias (78% vs. 52%), and an International Prognostic Scoring System (IPSS) risk score of intermediate-2/high (57% vs. 23%) compared with pMDS patients. Patients with sMDS have received 93 cycles of AZA, and as of this analysis, have received a median of 4 cycles (range, 1–13). Most common dose and schedule was 75 mg/m 2 (81%), 7 days on treatment (39%) for patients with sMDS vs 75 mg/m 2 (88%), 5 days on (47%) for pMDS patients. Six of 15 (40%) sMDS patients with ≥ 56 days treatment duration had received a red blood cell (RBC) transfusion during the 6 months prior to AVIDA. Of these patients, 4/6 (67%) have achieved RBC transfusion independence. Conclusions: Patients with sMDS are being treated with AZA in the community-based setting with early data demonstrating substantial benefit in transfusion independence. [Table: see text]
A phase II study of nedaplatin (CDGP) and docetaxel (TXT) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: S. Fujino, Y. Asada, Y. Nakano, Y. Suzumura, S. Inoue, T. Nagao, T. Hajiro, N. Tezuka, S. Sawai
Journal: Journal of Clinical Oncology (2007)

7660 Background: Nedaplatin (CDGP) is a cisplatin derivative developed in Japan. In non-small cell lung cancer (NSCLC), its response as monotherapy has been reported to be 20.5%, while when used in combination with vindesine, its efficacy is similar to cisplatin (CDDP). With respect to adverse effects, it causes less nausea/vomiting and nephrotoxicity compared to CDDP. By these data, we conducted a phase II study of combination treatment with CDGP and docetaxel (TXT) in advanced NSCLC. Methods: Forty six patients (Male/Female 39/7, median age 65 years (40–79), IIIB/IV 20/26) were enrolled from March 2004 to March 2006. Eligibility criteria included signed informed consent, age over 20 and under 80, measurable disease, ECOG PS 0–1, adequate bone marrow reserve, no previous chemotherapy or radiotherapy, and life-expectancy of at least 12 weeks. Treatment consisted of 80 mg/m 2 CDGP and 60 mg/m 2 TXT on day one with about 1,000 ml of hydration every 3–4 weeks. Results: One hundred and forty four cycles were given to 46 pts (mean cycles 3.1) and the mean dosages actually administered were 75.5±6.1 mg/m 2 for CGDP and 57.7±4.6 mg/m 2 for TXT. An over all response rate was 52.2% (squamous cell carcinoma 66.7%, adenocarcinoma 44.0%), median survival time was 12 months and 1-year survival rate was 50%. NCI-CTC grades 3–4 leukopenia, neutropenia, nausea/vomiting and appetite loss occurred in 44 (29.2%), 50 (34.7%), 5 (3.5%), 6 (4.2%) cycles, respectively. There was no grade 3–4 anemia, thrombocytopenia and neuropathy. Conclusions: This combination of chemotherapy was well tolerated, and its activity and survival for advanced NSCLC were acceptable. The update data will be presented at the meeting. No significant financial relationships to disclose.
Bortezomib, IV cyclophosphamide, and dexamethasone (VelCD) as induction therapy in newly diagnosed multiple myeloma: Results of an interim analysis of the German DSMM Xia trial
Authors: S. Knop, P. Liebisch, H. Wandt, M. Kropff, W. Jung, N. Kroeger, O. Sezer, C. Straka, G. Fingerle-Rowson, H. Einsele
Journal: Journal of Clinical Oncology (2009)

8516 Background: Cytoreductive induction followed by HD-MEL and ASCT is considered standard of care for younger patients (pts) with multiple myeloma (MM). The success of this combined procedure partially depends on the efficacy of induction treatment. Bortezomib-containing induction regimens have already been shown to be superior to standard VAD. In order to further improve the efficacy of induction treatment we combined Vel with intravenous (IV) cyclophosphamide (C) and dexamethasone (D). Methods: This trial is an open, prospective, multicenter, uncontrolled phase II/III study with a planned recruitment of 400 pts. The first 30 pts were included in the dose finding study to determine the optimum dose of IV C in conjunction with Vel and D. The following 170 pts up to 60 years of age with untreated MM were enrolled to receive 3 cycles of induction with Vel 1.3 mg/m2 IV d1, 4, 8, 11; D 40 mg/d d1, 2, 4, 5, 8, 9, 11, 12; and C 900mg/m2 IV d1. Primary study objective is response rate (≥ PR) to VelCD according to the EBMT criteria. Results: Data from the first completed 200 pts (mean age: 52 years; 74% stage III) from 36 German centers were analyzed as ITT population. Response rates are given in Table and were documented in 82% of the subjects with 13q-, in 94% with t(4;14) and in 70% with 17p-. SAEs (n=84) occurred in 24.5% of the pts and were related to Vel, C or D in 16%, 14.5% or 9.5% respectively. The mortality rate of 1% is low, 53% of the patients experienced grade 3 + 4 AEs, infections of grade 3 and 4 were reported in 2% and grade 3 paraesthesia occurred in 2%. Conclusions: This interim analysis demonstrates that bortezomib combined with dexamethasone and intravenous cyclophosphamide (VelCD) is a highly effective induction regimen for pts ≤ 60 years with newly diagnosed MM regardless of cytogenetic risk factors. [Table: see text] [Table: see text]
Genomic differences between smoking and drinking patients and non-smoking and non-drinking patients with oral tongue cancer
Authors: R. L. Foote, X. Liang, A. O'Reilly, A. Leightner, J. Lewis, D. Smith, D. Kademani
Journal: Journal of Clinical Oncology (2008)

22157 Background: There has been a reported increase in the incidence of tongue cancer, especially in a much younger population that have not been exposed to the traditional risk factors –cigarette smoking and alcohol use. The aim of this study is to identify the genomic differences between oral tongue cancers depending upon whether the patient had a history of smoking and/or drinking or not. Methods: Fresh frozen tissue from 12 patients with squamous cell carcinoma of oral tongue who underwent an operation between January 2004 and December 2006 were examined. DNA and high quality RNA was isolated from oral tongue tumors (cut to be greater than 80% tumor) and matched normal tissue from each of 6 patients with a drinking and smoking history and 6 younger patients without a drinking and smoking history was examined. Gene Expression Profiling (Affymetrix U133 Plus 2 arrays) and Array Comparative Genomic Hybridization (aCGH) using the Agilent platform were performed to analyze genome-wide alterations between these two distinct cohorts. Results: Gene expression profiling analysis was performed. Using a paired t-test, there were a total of 5,767 transcripts with p ≤ 0.05 in the non-drinking and non-smoking patients, and 4,329 transcripts with p ≤ 0.05 in the drinking and smoking patients. We found that 7 genes were up-regulated and 6 genes were down-regulated in the drinking and smoking patients only; and that 6 genes were up- regulated and 10 genes were down-regulated in the non-drinking and smoking patients only. The aCGH data showed that 1p32.2–1p36.12; 3q26.31–3q27.2; 3q28; 4p15.33–4p13; 5p15.32–5p15.2; 7p12.1; 9q22.2–9q21.13; 9q34.2; 11q14.1–11q12.2;16p13.2–16p12.1; 18p11.31; Xq12–Xq21.1 were regions of major difference between drinking/smoking and non-drinking/smoking patient samples. Conclusions: Genome-wide alterations are highly heterogeneous and vary significantly between the two patient groups. Thus, it is likely that different key genes and pathways are involved in oral tongue cancers related to tobacco and alcohol use and oral tongue cancers not related to tobacco and alcohol use. However, the results obtained need to be further validated in a larger number of oral tongue cancer samples. No significant financial relationships to disclose.
Aquaporin-2 in the immature rat
Authors: M Bonilla-Felix, W Jiang
Journal: Journal of the American Society of Nephrology (1997)

The immature kidney is resistant to arginine vasopressin. To define the role of aquaporin-2 (AQP-2), the developmental expression of this water channel was studied in rats. AQP-2 levels were lower during early postnatal life, reaching maximal expression at 10 wk of age. Concurrently, urine osmolality increased from 242 +/- 60 to 1267 +/- 311 mosmol/kg. To study the regulation of AQP-2, immature and adult rats were kept on ad libitum intake or were water-deprived. Under normal conditions, AQP-2 levels in the immature rat were significantly lower (52.3 +/- 5.8%, P < 0.001) than in the adult. However, after dehydration the expression increased to adult levels. Interestingly, the increase in AQP-2 observed in the immature kidney was not accompanied by a proportional increase in urine osmolality. To rule out a potential alteration in AQP-2 trafficking, the transport of this water channel was investigated in a group of rats subjected to dehydration, treated with desmopressin acetate (dDAVP), or water loaded. Dehydration and dDAVP stimulated translocation of AQP-2 from intracellular vesicles to the plasma membrane, whereas water loading caused a shift of AQP-2 channels back to intracellular vesicles in both adult and immature animals. In summary, AQP-2 expression and trafficking in the immature kidney is appropriately stimulated by water deprivation and dDAVP. However, urine osmolality remained significantly decreased. From this study, it is concluded that although AQP-2 expression may play a role in the development of urine concentrating abilities, there still is a significant defect, yet to be defined, distal to AQP-2.
A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer.
Authors: I F Tannock, N F Boyd, G DeBoer, C Erlichman, S Fine, G Larocque, C Mayers, D Perrault, H Sutherland
Journal: Journal of Clinical Oncology (1988)

This study was designed to assess the role of dosage of chemotherapy for treatment of metastatic breast cancer. One hundred thirty-three patients without prior chemotherapy for metastatic disease were randomly allocated to receive two different dose levels of cyclophosphamide (C), methotrexate (M), and fluorouracil (F), administered intravenously (IV) every 3 weeks. Patients were stratified by sites of disease (visceral, bone, or soft-tissue dominant) and by interval from primary surgery to first recurrence. Doses on the higher-dose arm were 600 mg/m2 (C,F) and 40 mg/m2 (M) with escalation if possible; doses on the lower-dose arm were 300 mg/m2 (C,F) and 20 mg/m2 (M) without escalation. Patients who failed to respond to lower-dose CMF were crossed over to the higher-dose arm. Patients randomized to the higher-dose arm had longer survival measured from initiation of chemotherapy (median survival, 15.6 months v 12.8 months, P = .026 by log-rank test), but the effect of dose was of borderline significance (P approximately 0.12) when adjusted for a chance imbalance between the two arms in the time from first relapse to randomization, using the Cox proportional hazards model. Response rates (International Union Against Cancer [UICC] criteria) for patients with measurable disease were higher-dose arm: 16/53 (30%) and lower-dose arm: 6/53 (11%), (P = .03). Only one of 37 patients responded on crossover from the lower- to the higher-dose arm. Patients experienced more vomiting, myelosuppression, conjunctivitis, and alopecia when receiving higher doses of chemotherapy. A series of 34 linear analogue self-assessment scales were used to make detailed quality of life assessments on a subset of 49 patients. These scales confirmed greater toxicity in the immediate posttreatment period, but also a trend to improvement in general health and some disease-related indices, in patients receiving higher-dose chemotherapy. This trial suggests that better palliation is achieved by using full-dose chemotherapy.
Seroepidemiologic Studies of Epstein-Barr Virus Antibody in Monkeys&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: John C. London, Louise B. Malan
Journal: JNCI Journal of the National Cancer Institute (1971)

The presence and distribution of antibody to the Epstein-Barr virus (EBV) in a simian colony were studied by use of fluorescent antibody techniques. Macaques in close contact with man and other simians were consistently positive for antibody to EBV. Newborn animals, when maintained in isolation, had antibodies persisting for less than 3 months in 60% of the cases. At 8–10 months, antibodies to EBV were essentially absent and remained so. These results of this study indicate an age and containment relationship to the presence of EBV antibodies.
Fetal Risks, Relative Risks, and Relatives' Risks
Authors: Howard Minkoff, Mary Faith Marshall
Journal: The American Journal of Bioethics (2016)

Several factors related to fetal risk render it more or less acceptable in justifying constraints on the behavior of pregnant women. Risk is an unavoidable part of pregnancy and childbirth, one that women must balance against other vital personal and family interests. Two particular issues relate to the fairness of claims that pregnant women are never entitled to put their fetuses at risk: relative risks and relatives' risks. The former have been used-often spuriously-to advance arguments against activities, such as home birth, that may incur risk; the latter implicate the nature of relationships in determining the acceptability of coercing or precluding activities. Motivated reasoning by clinicians and judges leads to inaccurate risk assessments, and judgments based on false claims to objectivity. Such judgments undermine the moral and legal standing of pregnant women and do not advance the interests of fetuses, pregnant women, families, or states.
The use of a live listeria vaccine in the treatment of cancer.
Authors: J. Rothman
Journal: Journal of Clinical Oncology (2010)

e15542 Background: If the objective of cancer immunotherapy is to make cancer appear to the immune system as an infection, then attenuated live Listeria monocytogenes (Lm) vaccines confer an advantage. Over 20 years of laboratory research have shown Lm to engender therapeutic immune responses by strongly stimulating both arms of the immune system, modifying the tumor microenvironment making it susceptible to attack, and exerting varied effects on marrow, vasculature, and elsewhere. Recently the first of these agents has been tested in humans. The clinical results, to date are consistent with the pre-clinical results. Methods: ADXS11-001 (Lm-LLO-E7), an attenuated live Lm vaccine that secretes a fusion of a non-hemolytic fragment of LLO fused to HPV-16 E7, was used in a phase I trial with a sub-therapeutic regimen comprised of 2 IV infusions of ADXS11-001 at a 3 week interval and followed by ampicillin and observation for 3 months to treat 15 women with metastatic cervix cancer who failed cytotoxic therapy and passed anergy testing. 3 doses were tested. Results: Live Lm vaccine was well tolerated. AE were comprised of a dose related flu-like syndrome that responded to symptomatic treatment without antibiotics. While not powered for efficacy assessment; 4 of 13 pts evaluable for efficacy demonstrated tumor reductions with 1 PR. Median survival was ∼2x greater than historical survival and 1 yr survival was ∼10x greater than historical survival. 2 women lost lesions. Clinical response was not dose related. Conclusions: Unlike other bacteria that have been tried, attenuated Lm is safe for clinical use and has a uniquely appropriate life cycle for use as a therapeutic live vaccine vector; as demonstrated in this study of very sick progressive cancer patients. In a patient population unresponsive to other therapies ADXS11-001 manifest a distinct efficacy signal that supports additional development efforts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Advaxis
Arbitrarily primed DNA fingerprinting for phylogenetic reconstruction in vertebrates: the Xiphophorus model.
Authors: R L Borowsky, M McClelland, R Cheng, J Welsh
Journal: Molecular Biology and Evolution (1995)

Arbitrarily primed PCR (AP-PCR or RAPD) is a technique for producing species-specific DNA fingerprints. We tested the utility of AP-PCR as a source of phylogenetically informative characters in three separate experiments, using fishes of the genus Xiphophorus. We chose Xiphophorus as a standard of comparison, because evolutionary relationships within the genus have been studied repeatedly using a variety of techniques. We compared our results to a "classical" phylogenetic hypothesis synthesized from studies using morphological, pigmentation, and allozyme characters, and to a recent conflicting hypothesis constructed from DNA sequence data. The sequence-based hypothesis places the southern swordtail Xiphophorus clemenciae squarely within the platyfish, whereas the classical hypothesis separates the two groups. In addition, the two hypotheses differ in their clustering of species of northern swordtails. Our findings are in close accord with the classical hypothesis. Our results allow the strongest phylogenetic hypothesis yet for Xiphophorus and demonstrate the utility of AP-PCR for studying species relationships within vertebrate genera.