tbuckley/cabot-search huggingface dataset:
Correlation of overall survival (OS) with bone marrow blast (BMBL) response in patients (pts) with myelodysplastic syndrome.
Authors: Lewis R. Silverman, Pierre Fenaux, Peter Greenberg, Erin P Demakos, Valeria Santini, John Francis Seymour, Shyamala Chendal Navada, Michael E. Petrone, Barbara R Snyder, Nozar Azarnia, Guillermo Garcia-Manero
Journal: Journal of Clinical Oncology (2015)

7017 Background: BMBL % is the prognostic variable with the greatest impact on outcome in MDS patients at diagnosis and subsequent time points. Current composite response criteria (IWG, Cheson 2006) do not consistently correlate with OS. Treatment impact of BMBL as an independent response criterion has not been adequately evaluated. Methods: We evaluated the correlation between OS and BMBL in pts with higher-risk (HR) MDS from 4 datasets from 7 studies with 887 pts: ONTIME, a Phase III randomized study of 2nd-line rigosertib (RIG) vs best supportive care (BSC) (N = 299; Silverman, ASH 2014); 4 Phase I/II studies of RIG in pts with MDS/AML (N = 39; Silverman, Hematol Oncol 2014); AZA-001, a Phase III study of azacitidine (AZA) vs 3 conventional care regimens (N = 358; Fenaux, Lancet Oncol 2009; Gore, Haematologica 2013); Cancer & Leukemia Group B (CALGB) Study 9221, a Phase II, randomized trial of 1st-line AZA vs BSC (N = 191; Silverman, J Clin Oncol 2002). Change in blasts was defined similarly: BM complete response is BMBL ≤ 5% and ≥ 50% decrease from baseline; BM partial response is ≥ 50% decrease from baseline, but BMBL still > 5%; stable disease is < 50% decrease or increase from baseline. Results: In ONTIME, landmark time-dependent analyses showed correlation of BMBL response/stabilization with OS at 4 wks (P= 0.011) and 12 wks (P< 0.001). In the 4 Phase I/II studies, BMBL response/stabilization at 4–8 weeks was associated with a quadrupling of median OS (P< 0.001). In Study AZA-001, time-dependent analysis of BMBL stabilization was associated with a significantly reduced risk of death in both treatment cohorts (P< 0.001). In Study 9221, landmark analysis of BMBL response/stabilization showed a 6-fold improvement in OS (P< 0.001). Conclusions: These studies, spanning more than a decade with different therapeutic agents and settings, demonstrate a consistent positive correlation between BMBL response and OS in pts with HR-MDS, including pts on supportive care. This suggests that use of reduction/ stabilization in BMBL can serve as a new early response parameter, as an intermediate clinical endpoint for evaluation of new agents, and as a biomarker for disease progression in HR-MDS itself.
Donor cell-derived hematological malignancy: a survey by the Japan Society for Hematopoietic Cell Transplantation
Authors: M Kato, T Yamashita, R Suzuki, K Matsumoto, H Nishimori, S Takahashi, K Iwato, C Nakaseko, T Kondo, K Imada, F Kimura, T Ichinohe, Y Hashii, K Kato, Y Atsuta, S Taniguchi, T Fukuda
Journal: Leukemia (2016)
Circulating Multiple Myeloma Cells (CMMCs): A Novel Method for Detection and Molecular Characterization of Peripheral Blood Plasma Cells in Multiple Myeloma Precursor States
Authors: Brendan Weiss, Kate Sasser, Chandra Rao, Brad Foulk, Steven Gross, Gayle Mallon, Colleen Erb, Anne Berkowitz, Patricia A. Mangan, Brenda K. Shelly, Adam D. Cohen, Dan T. Vogl, Alfred L. Garfall, Edward A. Stadtmauer
Journal: Blood (2014)
Randomized strategical trial of chemotherapy in metastatic colorectal cancer (FFCD 2000–05): Preliminary results
Authors: O. Bouché, M. Castaing, P. L. Etienne, P. Texereau, D. Auby, L. Bedenne, P. Rougier, D. Gargot, M. Gasmi, M. Ducreux
Journal: Journal of Clinical Oncology (2007)

4069 Background: The survival benefit of using a combination therapy instead of keeping it for a second line (L2) has not been demonstrated in metastatic colorectal cancer. The purpose of this trial was to compare the efficacy of simplified LV5FU2 (s) followed by FOLFOX6 (arm A) to FOLFOX6 followed by FOLFIRI (arm B) on progression-free survival after two lines of chemotherapy. We present here preliminary results relating to toxicity, observance and overall survival. Methods: Inclusion criteria: a) non resectable metastases of histologically proven colorectal adenocarcinoma , b) evaluable disease (WHO criteria), c) absence of previous chemotherapy other than adjuvant. Treatment was as follows: LV5FU2s = at day 1, folinic acid 400 mg/m 2 , 5-FU bolus 400 mg/m 2 and continuous infusion over 46 hours 2,400 mg/m 2 /2 weeks; FOLFOX6 = LV5FU2s + oxaliplatin 100 mg/m 2 at day 1; FOLFIRI = LV5FU2s + irinotecan 180 mg/m 2 at day 1. Results: 410 pts out of 570 initially planned (early stopping due to slow accrual and new treatments) were included from 02/2002 to 02/2006 (205 in each arm). Median follow-up was 25 months. The median number (range) of cycles (28 days) in first line (L1) was respectively 5 (1–24) and 6 (1–24) in the arms A and B (p=0.01), and for L2 (152 and 144 pts in the arms A/B): 5 (1–17) and 3 (1–33) (NS). In the arms A and B, 74% and 70% of pts had L2. L1 was stopped for toxicity for 1% and 16% of the pts in arms A and B (p&lt;0.0001); L2 respectively for 15% and 2% pts (p&lt;0.0001). The percentages of pts presenting at least a grade 3–4 hematologic toxicity (mainly neutropenia) by arm were: 6% versus 37% (p&lt;0.0001) for L1 and 30% versus 27% (NS) for L2; grade 3–4 non hematological toxicity (grade 2–4 neurotoxicity): 26% (1%) versus 56% (64%)(p&lt;0.0001; p&lt;0.0001) for L1 and 54% (60%) versus 46% (40%) of the pts for L2 (NS; p&lt;0.01). No toxic death was observed in the arm A against 5 in the arm B: 3 in L1 and 2 in L2. Overall survival medians were 17 and 16 months in arms A/B (logrank p=0.64) (preliminary results, 291 observed deaths). Conclusions: This trial does not show any substantial difference in treatment duration and overall survival between both arms and shows a more important toxicity in the arm with first line combined chemotherapy. No significant financial relationships to disclose.
Recent Selection Changes in Human Genes under Long-Term Balancing Selection
Authors: Cesare de Filippo, Felix M. Key, Silvia Ghirotto, Andrea Benazzo, Juan R. Meneu, Antje Weihmann, Genís Parra, Eric D. Green, Aida M. Andrés
Journal: Molecular Biology and Evolution (2016)

Balancing selection is an important evolutionary force that maintains genetic and phenotypic diversity in populations. Most studies in humans have focused on long-standing balancing selection, which persists over long periods of time and is generally shared across populations. But balanced polymorphisms can also promote fast adaptation, especially when the environment changes. To better understand the role of previously balanced alleles in novel adaptations, we analyzed in detail four loci as case examples of this mechanism. These loci show hallmark signatures of long-term balancing selection in African populations, but not in Eurasian populations. The disparity between populations is due to changes in allele frequencies, with intermediate frequency alleles in Africans (likely due to balancing selection) segregating instead at low- or high-derived allele frequency in Eurasia. We explicitly tested the support for different evolutionary models with an approximate Bayesian computation approach and show that the patterns in PKDREJ, SDR39U1, and ZNF473 are best explained by recent changes in selective pressure in certain populations. Specifically, we infer that alleles previously under long-term balancing selection, or alleles linked to them, were recently targeted by positive selection in Eurasian populations. Balancing selection thus likely served as a source of functional alleles that mediated subsequent adaptations to novel environments.
Abstract 12922: Noninvasive Risk Stratification of Lethal Ventricular Arrhythmias using 64-channel Magnetocardiography in Patients with Dilated Cardiomyopathy
Authors: Yosuke Otsuka, Takeshi Aiba, Hiroshi Takaki, Ikutarou Nakajima, Kohei Ishibashi, Kouji Miyamoto, Yuko Yamada, Hideo Okamura, Takashi Noda, Kazuhiro Satomi, Toshihisa Anzai, Masaharu Ishihara, Satoshi Yasuda, Hisao Ogawa, Kengo Kusano, Wataru Shimizu, Shiro Kamakura, Masaru Sugimachi
Journal: Circulation (2013)

Background: Heterogeneity of ventricular repolarization is known to be one of the potent arrhythmic substrates in idiopathic dilated cardiomyopathy (DCM). However, non-invasive evaluations of the r...
Remnant kidney oxygen consumption
Authors: R M Culpepper, A C Schoolwerth
Journal: Journal of the American Society of Nephrology (1992)

On the basis of observations in surgically created remnant kidneys of rat and dog, a novel hypothesis for progressive injury in the setting of reduced renal mass has been put forth. Both rat and dog remnant kidneys exhibit significant hypertrophy that is accompanied by an increased rate of oxygen consumption (QO2) per remaining nephron but not per gram of tissue. This putative "hypermetabolism" is seen in the face of progressive scarring of the tubulointerstitial compartment of the remnant kidney, and interventions that reduce QO2 in these models have been associated with reduced tissue injury in previous studies. The proposed pathway by which an increase in QO2 leads to cellular damage is via the production of oxygen-reactive species or free radicals. In this article, the available data upon which this "hypermetabolism" hypothesis is based are reviewed and the constructs within which these data have been analyzed are examined. From these considerations, a set of questions not yet answered that may serve to direct more fruitful query into this intriguing problem
Sleep diversity index for fragmentation analysis
Authors: Roomila Naeck, Daniel D'Amore, Marie-Françoise Mateo, Antoine Elias, Arnaud Rabat, Jean-Marc Ginoux
Journal: European Respiratory Journal (2013)

Introduction: Sleep fragmentation is one of the main problems of sleep disorders especially in respiratory failure. During this last decade, several indicators of sleep fragmentation were introduced but none of them seems to take into account the succession of sleep stages. To tackle with this problem, we used the Shannon entropy index for modelling sleep stages diversity from an hypnogram and for assessing more accurately sleep quality by quantifying its fragmentation.

Methods: This study was conducted at the sleep laboratory of the Centre Hospitalier Intercommunal de Toulon la Seyne. 100 polysomnographies under spontaneous breathing were analysed: 55 from normal subjects and 45 from patients with obstructive sleep apnea who came for a diagnosis. The hypnogram was sampled every 15 epochs. The Shannon entropy index (Sh) was then calculated for each sample. We noticed that entropy varies between two extrema: a minimum value (zero) corresponding to an absence of changing in sleep stages and a maximum value corresponding to the equiprobability of occurrence of sleep stages (ShMax). We define the Sleep Diversity Index (SDI) as being equal to the proportion of time spent at an entropy Sh > 1/2 ShMax for the total duration of the recording.

Results: First, a statistical test of linear correlation has highlighted a very strong anti-correlation (r = - 0.88, p < 0.01) between the SDI and the sleep efficiency index defined by the ratio between total sleep time and time spent in bed.

Then, using the receiver operating characteristic (ROC) curves, the IDS threshold of fragmentation was determined at 17.57%.

Conclusion: If IDS is lower than 17.57%, then sleep is considered as non-fragmented and otherwise, sleep is considered as fragmented.
Antitumor activity of imatinib in progressive, highly expressing KIT adenoid cystic carcinoma of the salivary glands: A phase II study
Authors: J. M. Guigay, F. Bidault, S. Temam, F. Janot, E. Raymond, S. Faivre
Journal: Journal of Clinical Oncology (2007)

6086 Background: Adenoid cystic carcinoma (ACC) of the salivary glands is a rare orphan disease of the head and neck usually resistant to conventional chemotherapy, that was found to express KIT in 87% (39/45) of cases in our institutions. Methods: This study explored the antitumor effects of imatinib given at 800 mg daily in a phase II study for patients (pts) with recurrent or metastatic ACC failing locoregional treatments, presenting CT-scan documented progressive disease and highly (50–100% of tumor cells) expressing KIT. Primary endpoint of this study was time to tumor progression, secondary endpoints were tumor response and safety. Results. Since 2004, 17 pts (M/F: 5/12, median age 48, range 33–71) were included. Target lesions were pulmonary metastasis (13 pts), renal metastasis (1 pt), locoregional (2 pts) and pulmonary + locoregional (1 pt) recurrences. Previous treatment with chemotherapy was reported in 5 pts. Median duration of treatment was 6 months (range, 1–14 months). Toxicity was mild to moderate except for 2 pts who had grade 3–4 anemia/neutropenia and asthenia requiring dose reduction and early study withdrawal, respectively. Among 15 evaluable pts with tumor progression at study entry, 5 pts were stable after 6+, 8, 9, 12+ and 18+ months of follow-up and 2 pts displayed partial responses of 42% and 35% (RECIST). These objective responses were associated with early symptomatic improvement (dyspnea/pain) and occurred in platinum- resistant pulmonary metastasis and a radiation-pre-treated locoregional recurrence, lasting 14 months and 9+ months, respectively. Final accrual and TTP determinations are ongoing. Conclusion. Although sporadic, objective responses can be observed in patients with progressive ACC treated with imatinib as well as long-lasting tumor stabilisations. No significant financial relationships to disclose.
Abstract 126: Functional Properties of Cardiac Stem Cell Niches in the Young and Old Heart
Authors: Junghyun Kim, Hanqiao Zheng, Donato Cappetta, Fumihiro Sanada, Christian Arranto, Narasimman Gurusamy, Polina Goichberg, Toru Hosoda, Marcello Rota, Jan Kajstura, Piero Anversa, Annarosa Leri
Journal: Circulation Research (2013)

Cardiac stem cells (CSCs) are clustered in interstitial structures, in which cardiomyocytes and fibroblasts act as supporting cells. However, the effects of the niche microenvironment on the functional properties of CSCs are largely unknown and whether young and senescent myocytes affect differently CSC fate remains to be determined. To address this issue, cardiac niches were examined in young and old Fischer 344 rats. Clusters composed of two or more lineage negative CSCs were included in the analysis. Unexpectedly, from 4 to 28 months of age, the number of CSCs per niche increased nearly 2-fold. This expansion of the CSC pool took place despite the increase in the fraction of dying CSCs with age. Apoptosis of CSCs was restricted to cells expressing the senescence-associated protein p16 INK4a . However, the fraction of CSCs positive for p16 INK4a increased significantly, documenting that the process of clearance of senescent CSCs was inefficient in the old myocardium. The fraction of p16 INK4a -positive CSCs undergoing apoptosis decreased 3.5-fold with age, resulting in accumulation of senescent cells within the niche. These observations indicate that the pool of functionally competent CSCs able to contribute to myocyte turnover decreased with age. In an attempt to compensate for the higher myocyte loss occurring in aged hearts, p16 INK4a -negative CSCs proliferated 4-fold more in old than in young rats, experiencing progressive telomeric shortening. To define whether the fate of CSCs was dictated by the properties of the neighboring myocytes in the senescent heart, myocytes and CSCs were co-cultured for 3 days. With respect to CSCs plated alone, old myocytes enhanced 2.2-fold BrdU incorporation in co-cultured CSCs. This effect was less apparent with young myocytes. No significant differences in CSC apoptosis were seen. Comparable results were obtained when CSCs and myocytes were plated in Transwell systems. Importantly, old myocytes released more IGF-1 than young myocytes; blockade of IGF-1 receptor in CSCs attenuated significantly the positive impact of myocytes on CSC replication. Collectively, our findings indicate that the rate of accumulation of old CSCs is greater than the rate of their death leading to the formation of senescent niches and organ aging.
The NKG2D expression on CD8+ T cells and the efficacy of polysaccharide K (PSK) in gastric cancer
Authors: S. Tsujitani, T. Osaki, H. Saito, K. Fukuda, S. Tatebe, M. Ikeguchi
Journal: Journal of Clinical Oncology (2008)

3065 Some studies suggest that the immunoreceptor NKG2D expression on CD8+ T cells is down-regulated and this reduction may be involved in immune evasion in cancer patients. The present study was designed to investigate NKG2D expression on CD8+ T lymphocytes and its relationship to immune evasion in gastric cancer patients. NKG2D expression on both circulating and tumor-infiltrating CD8+ T cells was evaluated by multicolor flow cytometry. Soluble MHC class I chain-related gene A (MICA) in the sera was quantitated by ELISA. Transwell experiments were carried out to determine the effect of cancer cells on NKG2D expression. NKG2D expression on circulating CD8+ T cells was down-regulated and significantly correlated with IFN-gamma production in gastric cancer patients (r = 0.68; P = 0.007). NKG2D expression was closely related to undifferentiated cancer (P = 0.021) as was the depth of invasion (P = 0.012). There was no difference in soluble MICA between gastric cancer patients and normal controls. NKG2D expression on CD8+ T cells was remarkably reduced in the tissue of gastric cancer compared with peripheral blood (P = 0.046). Complete removal of tumor by surgery restored NKG2D expression on CD8+ T cells (P = 0.0049). Transwell experiments showed that this down-regulation was induced by direct contact between cancer cells and CD8+ T cells and that soluble factors did not affect the NKG2D expression. This phenomenon was blocked by the addition of anti-MICA antibodies. Furthermore, the NKG2D expression down-regulated by tumor cells was dose-dependently recovered by administration of non-specific immunopotentiator, polysaccharide K (PSK). Therefore, decreased NKG2D expression may be one of the key mechanisms responsible for immune evasion by tumors in gastric cancer. The NKG2D expression may be a promising biomarker for monitoring the efficacy of PSK. No significant financial relationships to disclose.
Are patients' needs being met after hours? An evaluation of phone calls made after hours for patients with thoracic malignancies.
Authors: Manali I. Patel, David Moore, Arnold Milstein, Heather A. Wakelee, Douglas W. Blayney
Journal: Journal of Clinical Oncology (2013)

46 Background: Understanding phone calls patients make after hours is important as it represents opportunities to provide improved care. Furthermore, better understanding of after-hours calls can help to influence reductions in healthcare spending. Therefore, we sought to evaluate the nature of after-hours calls to the thoracic oncology clinic. Methods: The study is a retrospective analysis of 4 months of phone calls made to the Stanford Cancer Institute during weekends and hours of 5pm-8am on weekdays. On-call physicians documented complaint, age, gender, and advice given. Phone calls were excluded from analysis if there were missing information. Differences in proportions were analyzed by Fisher's exact test. A two-sided p value &lt;0.05 was considered significant. Results: There were 271 phone calls made after-hours by patients with lung cancer however after exclusions, there were 215 calls for analysis. The majority of phone calls occurred between 5pm-11pm (n = 57; 173%) followed by daytime calls during the weekend (n = 37; 17%). A majority of phone calls were made by the patient (50%) with a slightly lower proportion made by family members (46%). The majority of patients who called were in their 50’s (29%) and female (54%). A high proportion of patients called for more than one complaint (30%) although almost all patients complained of more than one symptom on review of systems (95%). The main symptoms patients called for were cough (28%) and shortness of breath (27%). Of the phone calls, 62% (133) were referred to the emergency room. Of those patients referred to the emergency department, 77% (103/133) resulted in an admission. Conclusions: Most after-hours phone calls from patients with lung cancer are related to symptoms. A large proportion of patients who were referred to the emergency department subsequently required an admission. Analyses of call content, and of events leading to the after hours calls might help predict hospital admission in this group of patients, and will inform development of proactive interventions to improve the quality of care, patient-centered outcomes, and value.
Adjuvant systemic therapy for resectable breast cancer.
Authors: G Bonadonna, P Valagussa
Journal: Journal of Clinical Oncology (1985)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1985.3.2.259 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3881562 Adjuvant systemic therapy for resectable breast cancer. G BonadonnaxG BonadonnaSearch for articles by this author , P ValagussaxP ValagussaSearch for articles by this author https://doi.org/10.1200/JCO.1985.3.2.259 First Page PDF © 1985 by American Society of Clinical Oncology
Combination of rubidazone and cytosine arabinoside in the treatment of first relapse in acute myelocytic leukemia
Authors: S. Pavlovsky, I. Fernandez, V. Palau, M.T. Santarelli, R. De Bellis, G. Ruiz-Arguelles, S. Brandalise, E. Jimenez-Fonseca
Journal: Annals of Oncology (1991)
Clinical Relevance of Point Mutations in the Cytoplasmic Domain of the Granulocyte Colony-Stimulating Factor Receptor Gene in Patients With Severe Congenital Neutropenia
Authors: N. Tidow, C. Pilz, B. Teichmann, A. Müller-Brechlin, M. Germeshausen, B. Kasper, P. Rauprich, K.-W. Sykora, K. Welte
Journal: Blood (1997)
Efficacy of adjuvant immunochemotherapy with polysaccharide k (PSK) for patients with curatively resected gastric cancer
Authors: K. Oba, S. Teramukai, M. Kobayashi, T. Matsui, H. Nakazato, K. Ito, J. Sakamoto
Journal: Journal of Clinical Oncology (2006)

14038 Background: An anti-tumor effect of non-specific immunomodulators, mainly PSK and OK-432, via an immunological response has been reported and combination immunochemotherapy has been examined. However, the survival benefit of immunochemotherapy for patients with curatively resected gastric cancer was unclear in the world. We performed a meta-analysis in order to evaluate the survival effect of immunochemotherapy employing a biological response modifier Polysaccharide K (PSK) in Japan. Methods: We reassessed by means of meta-analysis of data with central randomization from 5164 patients enrolled in Japanese eight clinical trials. In all eight trials patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK. The endpoint was 5-year survival odds ratio. Data were analyzed by using a weighted average of the log odds ratios (using Peto’s method). Results: The 5-year odds ratio for all eligible patients was 0.88 (95% confidence interval: 0.78–0.98; p=0.021). There was a significant heterogeneity between the trials (p=0.016). Conclusions: The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve survival of patients with curatively resected gastric cancer. No significant financial relationships to disclose.