tbuckley/cabot-search huggingface dataset:
Addition of bortezomib to thalidomide, dexamethasone and zoledronic acid (VTD-Z regimen) significantly improves complete remission rates in patients with relapsed/refractory multiple myeloma
Authors: G. Teoh, D. Tan, W. Hwang, L. P. Koh, C. Chuah, H. J. Ng
Journal: Journal of Clinical Oncology (2006)

17537 Background: We previously treated 26 patients with relapsed/refractory multiple myeloma (MM) with thalidomide (Thal), dexamethasone (Dex) and zoledronic acid (Zol); dtZ regimen; and demonstrated an overall response rate of 75.0%. However, the rate immunofixation (IF)-negative complete remissions (CR) was only 7.7%. Recently, the bortezomib (Velcade) has been shown to be effective against MM. In this study, we added bortezomib (Vel) to dtZ (VTD-Z regimen) in a subgroup of patients to determine whether the CR rate can be improved. Methods: A non-randomized, single-arm study was conducted. Consecutive patients (n = 14) who either failed to achieve a partial response (PR) after 3 cycles; or CR after 9 cycles of dtZ were treated with 2 to 11 three-weekly cycles of VTD-Z; comprising: Vel 1.3 mg/m 2 on days 1, 4, 8 and 11; Thal 50 mg ON; Dex 20 mg OM on days 1 to 4, 8 to 11, 15 to 18; and Zol 4 mg on day 1. The primary study objective was to determine the maximal response rates (RR). The end-point of the study was maximum response, graded by Bladè’s criteria. Results: Fourteen patients (3 males, 11 females; median age 63.3 years) were studied. Complex karyotypes, including 5 patients with deletion of chromosome 13 (del(13)), were present in 11 patients at diagnosis. The overall RR was 92.9% (13 out of 14), of which 42.9% (6) achieved CR (p &lt; 0.001, chi-squared test). In addition, 21.4% (3) achieved near-CR (nCR), and 28.6% (4) achieved PR. There were no minimal responders (MR) and 1 (7.1%) non-responder (NR). Two patients who achieved CR had del(13). Painful grade 3 peripheral neuropathy was observed in 2 (14.3%) patients. Grade 1 and 2 peripheral neuropathy was observed in another 4 (25.0%) of patients; transient grade 3 thrombocytopenia was observed in 5 (35.7%) patients; and papular rashes were observed in 3 (21.4%) patients. The single NR was the only death that occurred during the period of study. Conclusions: Our study demonstrates that the VTD-Z regimen is exceptionally effective and safe in patients with relapsed/refractory MM. Addition of Vel to dtZ significantly increases the CR rate from 7.7% to 42.9%. These data suggest that combination of these 4 drugs may be at least additive, if not, even synergistic. No significant financial relationships to disclose.
Ultrastructural localization of H+ATPase in rabbit cortical collecting duct.
Authors: J W Verlander, K M Madsen, D K Stone, C C Tisher
Journal: Journal of the American Society of Nephrology (1994)

In contrast to results obtained in the rat kidney, studies of H+ATPase localization in the rabbit kidney have failed to demonstrate basolateral plasma membrane H+ATPase immunoreactivity in intercalated cells in the cortical collecting duct (CCD). Previous studies have relied on light microscopic immunofluorescence techniques, which have limited resolution. Therefore, the immunogold procedure was used to localize H+ATPase in rabbit collecting ducts at the ultrastructural level. Rabbit kidneys were preserved in vivo with periodate-lysine-paraformaldehyde or glutaraldehyde solutions, and samples of cortex were embedded in Lowicryl K4M. Thin sections were labeled for H+ATPase by the immunogold procedure with a rabbit polyclonal antibody against the 70-kd subunit of bovine brain H+ATPase. Three patterns of localization of H+ATPase were observed. The majority of intercalated cells in the CCD exhibited label over cytoplasmic vesicles only. In these cells, no label was associated with either the apical or basolateral plasma membranes. In a second group of cells, label for H+ATPase was observed along the basolateral plasma membrane and over cytoplasmic vesicles throughout the cell. Rarely, intercalated cells with H+ATPase label along the apical plasma membrane and over the apical cytoplasmic vesicles were observed in the CCD. In the initial collecting tubule and connecting segment, intercalated cells with either pronounced apical or basolateral plasma membrane label prevailed, whereas few cells exhibited label restricted to the cytoplasmic vesicles. In summary, in the rabbit CCD, three patterns of H+ATPase distribution exist in intercalated cells, two of which conform to published models of type A and type B intercalated cells.
Abstract 13: Baicalein Rescues Delayed Therapeutic Hypothermia in Cardioprotection
Authors: Jing Li, Changqing Li, Hsien-Hao Huang, Qiang Zhong, Xiangdong Zhu, Terry L Vanden Hoek, Zuohui Shao
Journal: Circulation (2012)

Introduction: Therapeutic hypothermia (TH) is a highly promising cardioprotective treatment for cardiac arrest and ischemia/reperfusion (I/R) injury. Our prior work showed that TH conferred cardiop...
Abstract 18872: Krúppel-like Factor 6 Promotes Obesity and Glucose Intolerance Through Adipocyte Differentiation
Authors: Junichi Ishida, Toru Suzuki, Kenichi Aizawa, Daigo Sawaki, Takayoshi Matsumura, Scott L Friedman, Ryozo Nagai
Journal: Circulation (2012)

Introduction: Obesity and diabetes mellitus are regarded as major risk factors for cardiovascular disease. Recent studies suggest a potential role for some Krüppel-like zinc-finger transcription factors (KLFs) in adipogenesis. KLF6 is ubiquitously expressed and is also suggested to promote adipocyte differentiation in vitro . However, the metabolic roles of KLF6 in vivo have yet to be addressed. Hypothesis: We assessed the hypothesis that KLF6 promotes obesity and pathogenesis of glucose intolerance through adipocyte differentiation. Methods: In the present study, we used heterozygote KLF6 knockout (KLF6 +/- ) mice and investigated whether KLF6 is involved in obesity in vivo . Results: On a normal diet, the body weight of KLF6 +/- mice was similar to that of wild-type mice (28.5 ± 2.8 g versus 30.9 ± 2.9 g, n=5 in each group. p=ns), however KLF6 +/- mice were resistant to high fat-induced obesity (39.8 ± 4.0 g versus 50.1 ± 3.7 g, n=7 in each group. p&lt;0.0002). As for food intake, there was no significant difference between two genotypes (2.9 ± 0.3 versus 3.2 ± 0.3 g/day, n=5 in each group. p=ns). Adipocytes from KLF6 +/- mice were smaller and showed a reduced hypertrophic response to this dietary manipulation, and adipocyte markers were less expressed in white adipose tissue of KLF6 +/- mice. Brown adipose tissue of KLF6 +/- mice also showed less steatotic change, which indicated enhanced heat production. On a high fat diet, KLF6 +/- mice and wild-type littermates were similar in fasting blood glucose levels, however KLF6 +/- mice showed significantly lower glucose concentrations after glucose challenge (27.5 ± 4.0 versus 13.1 ± 1.9 mmol / L, n=5 in each group . p=0.006). Serum adiponectin levels were markedly higher in KLF6 +/- mice (3.4 ± 0.7 versus 2.4 ± 0.3, n=8 in each group. p=0.03). Embryonic fibroblasts from KLF6 +/- mice were significantly impaired in adipogenic differentiation. Conclusions: KLF6 +/- mice showed no metabolic phenotype under a normal intake, whereas they were resistant to excessive nutrition, compared with wild-type littermate. KLF6 promotes adipocyte hypertrophy, which leads to the pathogenesis of obesity, glucose intolerance and diabetes mellitus.
Abstract 18474: Risk Factors for Long Term Morbidity After Pediatric Heart Retransplantation : Analysis from the International Society of Heart and Lung Transplantation Registry
Authors: Jennifer Conway, Leah B Edwards, Brian W McCrindle, Richard Kirk, Cedric Manlhiot, Anne I Dipchand
Journal: Circulation (2012)

Recent detailed analysis of the ISHLT registry has shown that retransplantation [ReTx] following pediatric primary heart transplantation [PTx] has inferior outcomes. Little is known about long-term morbidities following ReTx. Data from the ISHLT registry (1998-2010) were used to examine risk factors for long-term morbidities in all ReTx patients with a PTx at age &lt; 18 y. 9,966 transplants were reviewed: 9,248 PTx, 602 first ReTx and 32 second ReTx. Long term morbidities were significantly (p&lt;0.001) more common after ReTx than PTx including allograft vasculopathy [AV] (HR 2.8), late rejection (HR 2.0) and late renal dysfunction (HR 2.6); but not PTLD (HR 1.2, p=0.52). Factors associated with development of AV after ReTx included history of hypertension [HTN] pre-ReTx (HR 1.8, p=0.003), AV as the indication for ReTx (HR 1.96, p=0.003) , donor factors including HTN (HR 5.7, p=0.001) , diabetes (HR 5.7, p=0.005), cocaine use (HR 2.6, p=0.02), male donor to female recipient (HR 1.5, p=0.02); and post-ReTx factors including renal dysfunction (HR 1.8, p=0.002), hospitalization for infection (HR 2.7, p=0.04) and drug treated HTN (HR 1.6, p=0.05). Risk for late rejection after ReTx included CMV+ serology pre-ReTx (HR 1.7, p=0.03), donor CMV+ serology (HR 1.8, p=0.007), early rejection post-ReTx (HR 1.6, p=0.03), documented non-compliance (HR 3.6, p&lt;0.001), and later year of ReTx (HR 1.3, p&lt;0.001). Risk factors for late renal dysfunction included higher pre-ReTx creatinine (HR 1.3, p&lt;0.001), later year of ReTx (HR 1.1, p&lt;0.001), dialysis post-ReTx (HR 4.0, p&lt;0.001), drug treated HTN in follow-up (HR 3.4, p&lt;0.001), development of AV (HR 1.7, p=0.003) and hospitalization for infection (HR 4.1, p=0.008). In a multivariate model, no associations were found between duration of PTx (e.g. cumulative health burden) and any of the ReTx morbidities. ReTx following PTx in the pediatric age range is associated not only with inferior outcomes but also with a significant risk of long term morbidities. Further study of the key risk factors identified may help in patient and donor selection for ReTx with the goal to improve outcomes.
Palliative radiotherapy (PRT) at end of life (EOL): Benchmarks for a proposed metric.
Authors: Hsiang-Hsuan Michael Yu, Stephen T. Lutz, Peter Anthony Johnstone
Journal: Journal of Clinical Oncology (2014)

119 Background: The initiation of chemotherapy within 30 days of death is considered a marker of chemotherapy overuse by Quality Oncology Practice Initiative (QOPI). We have previously proposed that the same be considered for RT. However, existing data for PRT delivered at EOL are limited. Methods: We reviewed the published literature for articles reporting PRT at EOL, defined as being within 30 days of death. These articles may be considered as benchmarks for current practice. Results: Published data revealed that frequency of PRT at EOL ranges from 6.2% to 28.6% for adult patients, and an order of magnitude lower in pediatric patients. Many patients received prolonged treatment course, did not complete PRT, and several studies reported median time from PRT to death was less than 2 weeks. A single study reported that only 26% of the patients reported benefit of palliation. The table summarizes published data. Conclusions: Substantial variability exists in published rates and completion of PRT delivery at EOL. Future studies may improve therapy choices at EOL by focusing on efficacy of PRT in this cohort, various PRT techniques including hypofractionation, and clinical variables that predict RT palliation at EOL. [Table: see text]
Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis
Authors: Daniela Calderón Carrión, Yüksel Korkmaz, Britta Cho, Marion Kopp, Wilhelm Bloch, Klaus Addicks, Wilhelm Niedermeier
Journal: International Journal of Oral Science (2015)

The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.
Intraperitoneal Therapy for Stage III Ovarian Cancer: A Therapy Whose Time Has Come!
Authors: David S. Alberts, Maurie Markman, Deborah Armstrong, Mace L. Rothenberg, Franco Muggia, Stephen B. Howell
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.19.3944 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12351590 Intraperitoneal Therapy for Stage III Ovarian Cancer: A Therapy Whose Time Has Come! David S. AlbertsxDavid S. AlbertsSearch for articles by this author Maurie MarkmanxMaurie MarkmanSearch for articles by this author Deborah ArmstrongxDeborah ArmstrongSearch for articles by this author Mace L. RothenbergxMace L. RothenbergSearch for articles by this author Franco MuggiaxFranco MuggiaSearch for articles by this author Stephen B. HowellxStephen B. HowellSearch for articles by this author Show More University of Arizona Cancer Center, Tucson, AZThe Cleveland Clinic Foundation, Cleveland, OHJohns Hopkins Oncology Center, Baltimore, MDVanderbilt University Medical Center, Nashville, TNNew York University Medical Center, New York, NYUniversity of California San Diego, La Jolla, CA https://doi.org/10.1200/JCO.2002.20.19.3944 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
In Vivo Treatment With Granulocyte Colony-Stimulating Factor Results in Divergent Effects on Neutrophil Functions Measured In Vitro
Authors: Patrick J. Leavey, Karen S. Sellins, Gail Thurman, David Elzi, Andrew Hiester, Christopher C. Silliman, Gary Zerbe, J. John Cohen, Daniel R. Ambruso
Journal: Blood (1998)
Psychosocial Outcomes in Adult Survivors of Retinoblastoma
Authors: Jennifer S. Ford, Joanne F. Chou, Charles A. Sklar, Kevin C. Oeffinger, Danielle Novetsky Friedman, Mary McCabe, Leslie L. Robison, Ruth A. Kleinerman, Yuelin Li, Brian P. Marr, David H. Abramson, Ira J. Dunkel
Journal: Journal of Clinical Oncology (2015)

Survival rates for individuals diagnosed with retinoblastoma (RB) exceed 95% in the United States; however, little is known about the long-term psychosocial outcomes of these survivors.Adult RB survivors, diagnosed from 1932 to 1994 and treated in New York, completed a comprehensive questionnaire adapted from the Childhood Cancer Survivor Study (CCSS), by mail or telephone. Psychosocial outcomes included psychological distress, anxiety, depression, somatization, fear of cancer recurrence, satisfaction with facial appearance, post-traumatic growth, and post-traumatic stress symptoms; noncancer CCSS siblings served as a comparison group.A total of 470 RB survivors (53.6% with bilateral RB; 52.1% female) and 2,820 CCSS siblings were 43.3 (standard deviation [SD], 11) years and 33.2 (SD, 8.4) years old at the time of study, respectively. After adjusting for sociodemographic factors, RB survivors did not have significantly higher rates of depression, somatization, distress, or anxiety compared with CCSS siblings. Although RB survivors were more likely to report post-traumatic stress symptoms of avoidance and/or hyperarousal (both P < .01), only five (1.1%) of 470 met criteria for post-traumatic stress disorder. Among survivors, having a chronic medical condition did not increase the likelihood of psychological problems. Bilateral RB survivors were more likely than unilateral RB survivors to experience fears of cancer recurrence (P < .01) and worry about their children being diagnosed with RB (P < .01). However, bilateral RB survivors were no more likely to report depression, anxiety, or somatic complaints than unilateral survivors.Most RB survivors do not have poorer psychosocial functioning compared with a noncancer sample. In addition, bilateral and unilateral RB survivors seem similar with respect to their psychological symptoms.
WITHDRAWN: Distribution of enzymes and transporter regulating prostaglandin E2signaling in the mouse placenta throughout gestation
Authors: Mai Inagaki, Tomohiro Nishimura, Takeo Nakanishi, Shin-ichi Akanuma, Masanori Tachikawa, Ikumi Tamai, Ken-ichi Hosoya, Masatoshi Tomi, Emi Nakashima
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Gestational trophoblastic disease: Experience at a tertiary care center from a developing country
Authors: R. Hariprasad, K. Ganessan, A. Gupta, L. Kumar, S. Kumar, N. Bhatla, A. Kriplani, V. Kochupillai
Journal: Journal of Clinical Oncology (2007)

16041 Background: We retrospectively analyzed case records of patients diagnosed to have Gestational Trophoblastic Disease (GTD) to determine clinical characteristics, risk groups, treatment outcome, and reproductive function post treatment. Methods: Between Jan 1991 to Dec 2005, 102 patients (mean age: 28.2 years, range 19–50) were diagnosed to have GTD. 35 patients were nulliparous and 8 had prior molar pregnancy. Vaginal bleeding was the most common presenting symptom (77.5%). The antecedent pregnancy was vesicular mole in 50%, abortion - 34.3%, ectopic pregnancy - 4% and term pregnancy in 11.8% patients. The mean value of B hCG was 1225386 mIU/ml. The histopathology (n=85) was complete mole in 30, partial mole - 28, invasive mole- 9, PSTT -1 and choriocarcinoma in 17 patients. 68(66.7%) patients had non-metastatic disease. Sites of metastasis were - lung (38.2%), vagina (11%), brain (8.8%), liver (6.9%) and kidney, Urinary bladder and peritoneum in one patient each. According to modified WHO risk scoring - 78(76.5% had low risk and 24 (23.5%) were high risk. Results: Eighty-seven (85.3%) patients received chemotherapy using methotrexate with leucovorin (n=63), EMA/CO (n=19) and BEP (n=5). 77/87 (89.5%) achieved complete remission (CR) ; the response rate was higher in non-metastatic GTD (p&lt;0.05). Two of 7(28.6%) patients with liver and 5/9 (55,6%) of brain metastasis achieved CR. Two patients had grade III oral mucositis and diarrhoea with methotrexate. One patient died of Methotrexate hypersensitivity. 19 patients received second line chemotherapy using EMA/CO (n=11), EMA/EP (n=2), BEP (n=1), actinomycin-D (n=1) and MAC (methotrexate, actinomycin D and Cyclophosphamide) n=1; 14 patients achieved CR. At a mean follow up of 180 months, 5-year survival for patients with low risk is 100% and that of high risk is 95%. Eight patients had recurrent disease including recurrent molar pregnancy in four. 16 patients had 24 successful deliveries after completion of treatment and 10 of them were primiparae. No fetal abnormalities were found. We did not observe second malignancy or other therapy related sequele. Conclusions: Present study confirms excellent outcome for patients with gestational trophoblastic disease. The potential for childbearing is well maintained. No significant financial relationships to disclose.
Association between cancer stem-like cell gene expression and clinical outcome in localized prostate cancer: A nested case-control study.
Authors: Adrian Stuart Fairey, Dongyun Yang, Susan G. Groshen, Philip Kim, Navneet Virk, Lina Wang, Sue Ellen Martin, Craig Stephens, Janine Cooc, Amir Goldkorn
Journal: Journal of Clinical Oncology (2012)

31 Background: New biomarkers are needed to better predict outcome after radical prostatectomy for clinically localized prostate cancer. Recent data suggest that subpopulations of cancer stem-like cells (CSC) are present in prostate cancer, and the CSC phenotype has been associated with high tumorigenicity, drug resistance, and disease progression. We sought to determine whether the expression of genes associated with the CSC phenotype are associated with disease recurrence. Methods: A nested case-control study was performed. Cases were men who underwent radical prostatectomy and had disease recurrence (n=147). Controls were men who underwent radical prostatectomy and did not have disease recurrence (n=59). Cases and controls were matched based on D’Amico risk stratification group. Laser capture microdissection with mRNA extraction and quantitative RT-PCR were used to measure the expression of 9 novel candidate CSC-associated genes (Axin2, Bmi1, CD133, CD44a, CTNNB1, ITGA2, Nkx3-1, Notch1, TACSTD2) in formalin-fixed, paraffin-embedded radical prostatectomy specimens. The Wilcoxon test was used to examine the association between CSC-associated gene expression and D’Amico risk stratification group. The optimal chi-square approach and recursive partitioning analysis were used to determine the association between CSC-associated gene expression and disease recurrence. Results: Complete gene expression data were evaluable for 206 out of 261 patients (79%). The median age was 64 years (range, 42-78 years). High expression of TACSTD2 (p=0.04) and CD44a (p=0.05) were associated with D’Amico low risk group. The optimal chi-square approach showed that Axin2 was associated with disease recurrence (recurrence rate: Axin2 ≤ 3.83 = 80% versus Axin2 &gt; 3.83 = 43%, p=0.0015). Recursive partitioning analysis confirmed an association between Axin2 and disease recurrence. Conclusions: A novel finding of the current study was that a low gene expression level of Axin2 was associated with disease recurrence. High gene expression levels of TACSTD2 and CD44a were associated with D’Amico low risk group. Further analysis of the Wnt/beta-catenin pathway is ongoing in this cohort.