tbuckley/cabot-search huggingface dataset:
PCR of immunoglobulin heavy-chain (IgH) complementary determining region III (CDRIII) for diagnosis of meningeal dissemination (MD) in primary CNS lymphoma (PCNSL): A prospective evaluation
Authors: A. Korfel, L. Fischer, B. Gleissner, P. Martus, M. Novrousian, U. Krümpelmann, H. Klasen, H. Kirchen, E. Thiel
Journal: Journal of Clinical Oncology (2007)

2082 Background: The prognostic impact of MD in PCNSL is unclear. Cytomorphological examination of cerebrospinal fluid (CSF) cells is the gold standard for detection of MD. PCR for detection of a clonal B-cell population may represent a more sensitive and specific method for MD detection. Methods: CSF was collected by lumbar puncture before treatment in patients with newly diagnosed PCNSL of B cell type, histologically proven. CSF cytomorphological examination was performed by an experienced hematopathologist or neurologist immediately after sampling at the treating institution. A sample of native CSF was sent for PCR examination to our central moleculargenetic laboratory. Here, DNA from CSF cell pellets was extracted using commercially available kits. A seminested PCR of the IgH chain CDR III region was performed using the primers LJH in the first, VLJH in the second and FR3A in both PCR reactions. PCR products were subjected to an automated fluorescent fragment analysis (ALF) to detect a monoclonal vs. polyclonal pattern, and results were compared to conventional cytology. Results: From January 2001 to August 2006 CSF from 215 patients was collected. Here, data from the first 146 patients examined is presented ( Table ). MD was detected in 15 of 106 examined patients (14%) by cytomorphological evaluation and in 17 of 146 patients (11.6%) using PCR. In 8 patients with negative cytology the PCR product was monoclonal, and in 7 patients with positive cytology a polyclonal PCR product was found. Conclusion: The frequency of MD in PCNSL detected by PCR of the IgH CDR III region is low and comparable to that detected by cytomorphological evaluation. However, discordant PCR and cytology results are frequent. Thus, PCR analysis appears to be an important adjunct for MD diagnosis. [Table: see text] No significant financial relationships to disclose.
Metastatic bladder cancer (MBC) after radical cystectomy and adjuvant chemotherapy compared to MBC after cystectomy.
Authors: J. Arranz Arija, Y. Jerez Gilarranz, M. Riesco Martinez, J. Adeva Alfonso, R. González Beca, C. López López, S. Encinas García, A. Soria Lovelle, I. Marquez Rodas, L. Cabezón Gutierrez
Journal: Journal of Clinical Oncology (2010)

e15050 Background: A meta-analysis showed reduction in the risk of relapse and death, in patients (p) with muscle-invasive bladder cancer who received adjuvant chemotherapy (ACT) after radical cystectomy (C) versus C alone. However the outcome of p who relapse after both strategies have not been compared. Methods: We retrospectively analysed 218 p with MBC who relapsed either after C (129 p, 59.2%) or C-ACT (89 p, 40.8%). P with MBC at diagnosis were excluded of this analysis. Results: Both groups (C vs ACT) were comparable (p ns) in age (mean: 65.7y vs 64.3y), grade (G3-4: 95.3% vs 97.8%), isolated lymph node relapse (23% vs 20.2%), or presence of some visceral localization (peritoneum, liver, bone, brain, or skin: 76.7% vs 79.8%). Groups differed (p < 0.05) in sex (male 86% vs 94%) and histology (non-papillary 66,7% vs 79.8%). ECOG could not be properly recorded, but more p in the C group received only palliative care due to their bad performance status at diagnosis of metastatic disease (55.8% vs 37.1%, p = 0.009). Among p who received active treatment there was an unbalance in the first-line regimens used at relapse (MVAC-like 48% vs 13%, CDDP-GEM-like 44% vs 30%, and other, mainly with paclitaxel 8% vs 57%) because p in the ACT group had already received MVAC or CDDP-GEM after surgery. Despite these unbalances, there were not statistically significant differences in either overall or complete response (38.9% vs 33.4% and 18.5% vs 13.2% respectively). After a median follow-up of 43 m, 77.6% of p have died. Median cancer-related 0S and 95% CI from metastatic disease were 4 m vs 8 m (2.8 – 5.2 vs 6 – 10 m, log-rank p=0.035) for all p, and 11 m vs 14 m (7.6 – 14.4 vs 8.8 – 19.3 m, log-rank p ns) for p who receive active treatment at relapse. After adjusting for sex, histology, grade, isolated lymph node relapse, visceral metastases and active treatment, the hazard ratio of death of C vs ACT was 1.15 (95% CI: 0.84 – 1.57). Conclusions: In our series, p with MBC who relapsed after C and adjuvant chemotherapy had at least similar response to chemotherapy and overall survival than those who relapsed after radical cystectomy alone. No significant financial relationships to disclose.
Effectiveness of intrathecal ziconotide in malignant pain: A combined analysis of two controlled trials
Authors: A. W. Burton, B. Lemus, R. Fletcher, S. Chandler, T. Marmon
Journal: Journal of Clinical Oncology (2006)

8552 Background: Ziconotide is a nonopioid, N-type calcium channel blocker that inhibits neuronal calcium influx, thereby reducing neurotransmitter release at primary pain afferents. Clinical trials have shown ziconotide is useful in managing severe chronic pain, including nociceptive and neuropathic pain of malignant etiology. We reviewed the effectiveness of ziconotide using the Visual Analog Scale of Pain Intensity (VASPI: 100 mm=worst possible pain, 0 mm=no pain). Methods: Cancer patients from two double-blind, placebo-controlled trials (Studies 95–001 and 301) were analyzed. Study 95–001 used a fast titration scheme over 5 to 6 days, enrolling only patients with malignant pain due to cancer or AIDS. In Study 95–001, the initial dosing regimen was based on a pilot trial and was later modified due to the frequency of adverse events (AEs). The final slower titration, lower dosing regimen resulted in a reduced AE rate. Only patients from the final dosing regimen of Study 95–001 were included in this analysis. Study 301 used a slower titration scheme over 21 days, enrolling patients with malignant or nonmalignant pain. A two-sided, two-sample t-test was used to evaluate the null hypothesis that the mean percent change in VASPI score from baseline to end of titration for the ziconotide group was not significantly different from that of the placebo group (intent-to-treat population). Results: A total of 67 patients with malignant pain were treated in the trials; 51 (35 ziconotide, 16 placebo) had both baseline and end of titration VASPI scores. The ziconotide and placebo groups had similar mean baseline VASPI scores (75.5 and 75.8 mm, respectively). The mean percent improvement in VASPI score was 36.5% in the ziconotide group and 8.6% in the placebo group (p=0.0230). Conclusions: These results indicated that ziconotide was effective in relieving malignant pain. [Table: see text]
A hematopoietic cell–driven mechanism involving SLAMF6 receptor, SAP adaptors and SHP-1 phosphatase regulates NK cell education
Authors: Ning Wu, Ming-Chao Zhong, Romain Roncagalli, Luis-Alberto Pérez-Quintero, Huaijian Guo, Zhanguang Zhang, Christelle Lenoir, Zhongjun Dong, Sylvain Latour, André Veillette
Journal: Nature Immunology (2016)
Effects Of Helicobacter Pylori Eradication In Adult Patients With Acute Idiopathic Thrombocytopenic Purpura (ITP)
Authors: Minoosh Moghimi, Saeid Razavi Dizaji, Yousef Mortazavi, Saeideh Mazloomzadeh, Shaharbano Keyhanian, Mozhgan Alamsamimi
Journal: Blood (2013)
Incorporation of a Comprehensive Geriatric Assessment (CGA) into a randomized phase III trial for metastatic breast cancer: The PELICAN Study
Authors: M. de Wit, N. Harbeck, M. Scholz, W. Lerbs, U. Wedding, F. Honecker
Journal: Journal of Clinical Oncology (2009)

9551 Background: The PELICAN trial is a randomized phase III trial evaluating efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line therapy in patients (pts) with metastatic breast cancer who are not considered candidates for combination chemotherapy. Randomisation was stratified according to age (cut-off 65 years) and anthracycline pretreatment. CGA results and adverse events (AEs), dose reductions, and number of applied cycles were evaluated. Methods: CGA comprised data on activities of daily living (ADL), instrumental activities of daily living (IADL), ECOG and Karnofsky performance score, comorbidity (CIRS-G), and number of comedication. According to CGA, pts were classified into groups 1–3 (Balducci 2000). Associations of CGA groups and single CGA items with outcome measures were assessed using Fisher's exact test, Wilcoxon test, and logistic regression. Results: Results of 210 pts, mean age 61 years (SD 11; range 22–85) were analysed. According to CGA, 102 pts were considered fit (group 1, 72%), 21 compromised (group 2, 15%), and 19 frail (group 3, 13%). Age was associated neither with overall AEs, nor with dose reductions or number of applied cycles. However, the following significant associations were observed: any AE and number of comedication (p=0.026); less hand foot syndrome (HFS) and CGA group 2/3 (p=0.032); and more constitutional symptomes and age &gt;=65 as well as CGA group 2/3 (p=0.002 and 0.015, respectively). Comedication was the variable most frequently associated with single AEs (dermatology other than HFS, p=0.038; gastrointestinal, p=0.035; constitutional symptomes, p=0.002; pain, p=0.001; pulmonary, p&lt;0.0001; fatigue, p=0.01). Whereas no association between any item and dose reduction was found, CIRS-G grade 3–4 was associated with a reduced number of applied cycles (p=0.049). Conclusions: Incorporation of CGA into a phase III trial is feasible and yields information that would otherwise have been missed. Results of CGA should be validated prospectively in treatment algorithms for this population. [Table: see text]
Neoadjuvant weekly paclitaxel/cisplatin chemotherapy (WTP) with concurrent thoracic chemoradiation followed by surgical resection for stage IIIA (pN2) non-small cell lung cancer (NCLC): Phase II study
Authors: S. Kim, H. Sohn, C. Suh, J. Ryu, E. Choi, Y. Kim, D. Kim, S. Park, W. Kim, J. Lee
Journal: Journal of Clinical Oncology (2006)

17036 Background: To investigate the role of weekly chemotherapy with paclitaxel/cisplatin and concurrent thoracic radiation (RT) as neoadjuvant therapy before surgical resection for patients with N2-IIIA NSCLC. Methods: Patients with pathologically proven N2 (pN2) and operable stage IIIA NSCLC were eligible. Six weekly chemotherapy with paclitaxel (50 mg/m 2 )/cisplatin (20 mg/m 2 ) was given with concurrent thoracic RT (1.8 Gy/fraction once a day, 45 Gy) during 5 weeks. Chest CT, whole body PET were checked before and 3 weeks after chemoradiation. For the patients without clearing pN2 nodes or with pT3 after surgical resection, boost RT (20 Gy) was given. Results: From Jan. 2002 to Nov. 2005, 38 patients were enrolled. Median follow-up time was 20 months: gender (male: female, 30:8,), age (median 56, 42–67). Of them, 31 patients underwent surgical resection. Three patients showed brain metastasis during chmoradiation. Two patients refused surgical resection after chemoradiation. One patient showed severe radiation pneumonitis and was not fit for the operation. One patient showed lung to lung metastases before surgical resection. Of the 31 patients who underwent surgical resection, 14 (45.2%) showed pN0–1, and 7 (22.6%) showed pathologic complete remission (CR). Three year overall survival rate of all patients was 37.7% (median 35.9 months) and 3 year progression free survival was 34.2% (median 18 months). In univariate analysis, clearing N2 node and pathologic CR after surgery were the factors that could predict long-term survival. And the 2 nd PET after chemoradiaiton could not expect clearing N2 nodes after surgical resection: sensitivity 44%, specificity 46%. As toxicities of WTP, hypersensivity reaction to paclitaxel and pneumonia with neutropenia were noted in 1 patient each. Severe radiation pneumonits was noted in 4 (of them 3 were given 65 Gy). Conclusions: WTP followed by surgical resection for N2-stage IIIA NSCLC was feasible. Clearing N2 nodes or pathologic CR after surgical resection were the factors of long-term survival. The usefulness of 2 nd PET to expect the clearing N2 nodes was not adequate. No significant financial relationships to disclose.
Minor Physical Anomalies and Plasma Dopamine-Beta-Hydroxylase Activity in Hyperactive Boys
Authors: Judith L. Rapoport, Patricia O. Quinn, Friedhelm Lamprecht
Journal: American Journal of Psychiatry (1974)

In a group of 76 hyperactive boys, the presence of multiple minor physical anomalies (stigmata) was associated with severity of hyperactivity and with a history of childhood hyperactivity in the father or a history of early obstetrical difficulty in the mother. In addition, children with high stigmata scores had higher than normal mean plasma dopamine-β-hydroxylase (DβH) activity. DβH was not related to behavioral activity ratings but specifically to stigmata score. Both imipramine and methylphenidate significantly increased plasma DβH activity; however, clinical improvement did not parallel this change. The authors suggest that these children are an important subgroup within the behaviorally defined, heterogeneous population of hyperactive children.
Dasatinib (D) in combination with weekly (w) paclitaxel (P) for patients (pts) with metastatic breast carcinoma (MBC): A phase I/II study.
Authors: M. N. Fornier, P. G. Morris, A. Abbruzzi, G. D'Andrea, T. Gilewski, J. Bromberg, C. T. Dang, M. N. Dickler, L. Norton, C. Hudis
Journal: Journal of Clinical Oncology (2010)

1156 Background: Inhibition of SRC is a novel approach for MBC. Preclinically, the SRC inhibitor D + P had superior antitumor activity to either agent alone. We designed this phase I-II study to translate this observation. Methods: For phase I: pts with MBC, ECOG PS 0-1, normal hepatic, renal, marrow function were eligible. Pts with pleural/pericardial effusions were excluded. For phase II: pts had measurable, HER2-negative MBC, ≤2 prior rx for MBC. Cycle (C) consisted of wP 80 mg/m2 IV 3/4 weeks + D 70mg orally daily; escalating to 100 mg, 120 mg, and 150 mg in cohorts of 3 pts. Toxicity was assessed by CTCAE v3.0, response by RECIST. Results: 15 pts (14 females, 1 male) enrolled; median age 54 (range 35-74), median PS=1 (range 0-1). 11 (73%) pts rcvd prior adjuvant chemoRx. Pts rcvd a median of 3 prior rx for MBC (range 0-12). Pts rcvd median of 2 C of D + P (range 1-10). One DLT occurred at 150 mg (G3 fatigue); this cohort was expanded with no further DLTs to date. However, 1 pt had a skin reaction to D 150mg C2 and came off study. 1 pt developed G3 febrile neutropenia on D 150mg C2 and withdrew. Overall the most common Rx-related toxicities have been hematologic and low G (Table). 7 of 12 (58%) pts treated with D ≥100mg had diarrhea (3pts; G1, 4pts; G2). 3 pts developed edema (all G1, D≥120mg). 12 pts are evaluable for response; 3pts (25%) PR (2 prior taxane, progressed C7, 1 continues on C10), 4 pts (33%) SD. Conclusions: Treatment with wP and D is feasible in pts with MBC. 1 DLT occurred at D 150 mg but due to cumulative toxicities the phase II dose is 120 mg. Preliminary evidence of activity has been seen in taxane-pretreated pts. Pts with SRC+ tumors, or active SRC signaling could be more sensitive to this approach. AE Total N (%) G1 N (%) G2 N (%) G3 N (%) G4 N (%) ↑Glucose 15 (100) 7 (47) 8 (53) - - ↑ QTc 13 (87) 9 (60) 4 (27) - - ↑AST 11 (73) 9 (60) 2 (13) - - ↓Hb 11 (73) 8 (53) 2 (13) 1 (7) - ↓Leukocytes 11 (74) 7 (47) 3 (20) 1 (7) - Neuropathy 11 (73) 8 (53) 2 (13) 1 (7%) - Fatigue 10 (67) 6 (40) 2 (13) 2 (13) - ↓Albumin 8 (53) 7 (47) 1 (7) - - ↑ALT 8 (53) 6 (40) 2 (13) - - Skin toxicity 8 (53) 6 (40) 2 (13) - - Nausea 7 (47) 5 (33) 2 (13) - - ↓Phosphate 7 (47) 0 5 (33) 2 (13) - ↓Platelets 6 (40) 4 (27) 1 (7) 1 (7) - ↓Neutrophils 5 (33) 0 4 (27) 1 (7) - ↑Alk phos 4 (27) 3 (20) - 1 (7) - ↑Sodium 4 (27) 4 (27) - - - Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Characterization of Products Synthesized by Galactosyltransferase Purified From the Ascites of Ovarian Cancer Patients
Authors: S K Chatterjee, M Bhattacharya, J J Barlow
Journal: JNCI Journal of the National Cancer Institute (1986)

Galactosyltransferase purified from the ascites of ovarian cancer patients can use to an equal extent N-glycosidic glycoproteins, such as asialoagalactofetuin, and O-glycosidic mucin, such as asialo bovine submaxillary mucin (BSM), as acceptors. Thermal treatment and substrate competition experiments demonstrated that the same enzyme catalyzed the transfer of galactose to both types of acceptors. Alkaline borohydride treatment showed that, while the product with asialoagalactofetuin was totally resistant, about 90% of the product with asialo BSM was hydrolyzed by this treatment. Gel filtration of the released oligosaccharides on a calibrated Biogel P-2 column showed three peaks. One major oligosaccharide (O-2) of size 5.7 glucose U and two minor peaks (O-1 and O-3) of sizes 8.7 and 3.7 glucose U, respectively, were obtained. The oligosaccharides were doubly labeled, first by incubation with uridine-diphosphate [14C]galactose, followed by alkali treatment in the presence of [3H]borohydride. The doubly labeled oligosaccharides were separately purified by gel filtration and ion-exchange chromatography and digested with various exoglycosidases. The digested products were characterized by gel filtration and paper chromatography in three different systems. From these results, the structures of these oligosaccharides were computed as follows: O-1 = beta-galactosyl-beta-N-acetylglucosamine-galactosaminitol (sialic acid); O-2 = beta-galactose-beta-N-acetylglucosamine-galactosaminitol; O-3 = beta-galactose-galactosaminitol. These results suggest that the galactosyltransferase from the ascites of ovarian cancer patients catalyzes the transfer of galactose to N-acetylglucosamine, irrespective of whether it is a part of an N-glycan or an O-glycan.
Nanoparticle-targeted delivery of nonanticoagulant heparin and doxorubicin in doxorubicin-resistant breast cancer
Authors: D. J. Bharali, M. Yalcin, U. Dier, S. Mousa, S. Mousa, C. Hanko, P. Phillips, S. A. Mousa
Journal: Journal of Clinical Oncology (2009)

e11599 Background: In comparison to low molecular weight heparin (LMWH), non-anticoagulant heparin (NACH), originally developed in our laboratory, has minimal effects on hemostasis. Encapsulation of chemotherapeutic agents and NACH in biodegradable nanoparticles has tremendous potential in improving survival among the breast cancer patients. Furthermore, custom-made nanoparticles with a targeted moiety on the surface would enable us to increase the efficacy and decrease the adverse effects of doxorubicin. Methods: PLGA-PEG nanoparticles co-encapsulating NACH and doxorubicin were synthesized by double emulsion solvent evaporation method. The in vitro efficacy of these nanoparticles was examined in MCF-7 doxorubicin resistant (MCF-7R) cells using MTT cell viability assay. Confocal microscopy was used to examine the uptake of α v β 3 antibody conjugated nanoparticles in human dermal microvascular endothelial cells (HDMEC), which are known to over express α v β 3 integrins. Results: Size measurement by DLS revealed that these nanoparticles co-encapsulating doxorubicin and heparins to be 200–300 nm in size. Data from the MTT assays in MCF-7R cells showed synergy between NACH and doxorubicin when encapsulated in PLGA-PEG nanoparticles. Confocal imaging in HDMEC cells indicates that these nanoparticles have the potential to be used for site specific delivery to the tumor neovascularization. In vivo data in nude mice xenograft (MCF-7R) are shown in the table below (doses of doxorubicin and NACH injected subcutaneously were 0.625 mg/kg and 2.5 mg/kg body weight, respectively). Significant decrease in tumor weight was observed in the mice xenograft, when treated with α v β 3 conjugated nanoparticles co-encapsulating doxorubcin or to greater extent doxorubicin and NACH compares to its non encapsulated counterparts. Conclusions: These data indicated distinct improvement in the anti-tumor efficacy using α v β 3 site directed delivery doxorubicin and NACH encapsulted in PLGA-PEG nanoparticles. [Table: see text] No significant financial relationships to disclose.
Genome-wide introgression among distantly related Heliconius butterfly species
Authors: Wei Zhang, Kanchon K. Dasmahapatra, James Mallet, Gilson R. P. Moreira, Marcus R. Kronforst
Journal: Genome biology (2016)

Although hybridization is thought to be relatively rare in animals, the raw genetic material introduced via introgression may play an important role in fueling adaptation and adaptive radiation. The butterfly genus Heliconius is an excellent system to study hybridization and introgression but most studies have focused on closely related species such as H. cydno and H. melpomene. Here we characterize genome-wide patterns of introgression between H. besckei, the only species with a red and yellow banded 'postman' wing pattern in the tiger-striped silvaniform clade, and co-mimetic H. melpomene nanna. We find a pronounced signature of putative introgression from H. melpomene into H. besckei in the genomic region upstream of the gene optix, known to control red wing patterning, suggesting adaptive introgression of wing pattern mimicry between these two distantly related species. At least 39 additional genomic regions show signals of introgression as strong or stronger than this mimicry locus. Gene flow has been on-going, with evidence of gene exchange at multiple time points, and bidirectional, moving from the melpomene to the silvaniform clade and vice versa. The history of gene exchange has also been complex, with contributions from multiple silvaniform species in addition to H. besckei. We also detect a signature of ancient introgression of the entire Z chromosome between the silvaniform and melpomene/cydno clades. Our study provides a genome-wide portrait of introgression between distantly related butterfly species. We further propose a comprehensive and efficient workflow for gene flow identification in genomic data sets.
The awareness and knowledge levels of colorectal cancer (CRC) patients and their first-degree relatives (FDR) for CRC screening.
Authors: C. Arslan, S. Kilickap, D. Rama, S. Yalcin
Journal: Journal of Clinical Oncology (2010)

3629 Background: We aimed to determine awareness and knowledge levels of CRC patients and FDR on CRC screening. Methods: Patients who were being treated or followed at our center and their FDR were asked to complete a questionnaire on CRC screening with colonoscopy (SC). The clinical and demographic data of the patients were recorded and analyzed. Results: A total number of 406 CRC patients including 242 men (60%) and 164 women (40%) were enrolled. Mean age was 56 ± 11.8. The knowledge level and awareness of 1,940 persons (sibling n: 1,381 and parents n: 153) including patients and FDR were evaluated. 38% of the patients were aware of the increased risk of CRC for FDRs, and 88% of them recognized the benefit of SC for early diagnosis. But only 11% of the CRC patients had undergone examination for screening previously from the diagnosis of cancer. Parents and siblings had SC in 9% and 20% of the patients, respectively. Mean age of patients whose FDR underwent SC was lower than the patients whose FDR did not have SC (52 vs. 57; p < 0.001). The frequency of SC in FDR was 64% in patients having CRC under 35 years of age. Persons having a positive family history of CRC had SC more often (51 vs. 22%, p < 0.001). FDR of patients having an educational level of high school or higher had SC more frequently (p = 0.017). The FDR of patients with higher income levels had SC twice more often than the patients having lower income (36 vs. 18%, p < 0.001). Conclusions: Significant relationship with SC and educational and income levels, and patient age was detected. There is an immediate need for raising the knowledge and awareness of patients and relatives. No significant financial relationships to disclose.