tbuckley/cabot-search huggingface dataset:
Human infection with novel G3P[25] rotavirus strain in Taiwan
Authors: F.-T. Wu, K. Bányai, J.C. Huang, H.-S. Wu, F.-Y. Chang, C.A. Hsiung, Y.-C. Huang, J.-S. Lin, K.-P. Hwang, B. Jiang, J.R. Gentsch
Journal: Clinical Microbiology and Infection (2011)
Uracil-tegafur in gastric carcinoma: a comprehensive review.
Authors: H Takiuchi, J A Ajani
Journal: Journal of Clinical Oncology (1998)

PURPOSE The second-generation oral anticancer agent UFT, a combination of uracil and tegafur (TGF), results in a higher fluorouracil (5-FU) concentration in the tumor tissues than is achieved by TGF or comparable doses of intravenous 5-fluorouracil. UFT has been extensively studied in Japan and has been in use in the Orient for many years, particularly for patients with gastric carcinoma. UFT has recently entered extensive investigations in North America and Europe. METHODS Relevant studies that have chronicled the establishment of UFT, its mechanism of action, preclinical toxicology, human pharmacokinetics, phase I studies, and activity against gastric carcinoma are described in detail. RESULTS The uracil in UFT slows degradation of 5-FU by dihydropyrimidine dehydrogenase (DPD), which results in sustained concentrations of 5-FU in blood and tumor tissues. UFT is well tolerated, but such toxic effects as nausea, vomiting, and diarrhea are dose- and schedule-dependent. In phase I pharmacokinetic studies, UFT given orally on a 28-day schedule resulted in blood concentrations comparable to those following low-dose continuous intravenous infusion of 5-FU. In patients with gastric carcinoma, UFT alone has a response rate of approximately 20%. In the adjuvant setting, UFT plus mitomycin appears superior to TGF plus mitomycin. In Japan, UFT is part of the standard adjuvant chemotherapy for gastric carcinoma. CONCLUSION UFT is one of the first second-generation oral 5-FU prodrugs under investigation in North America and Europe. The literature suggests UFT is well tolerated and has cellular pharmacokinetic superiority over the first-generation 5-FU prodrug TGF. UFT has a more favorable toxicity profile than intravenous 5-FU. The issues of efficacy, patient convenience, and quality of life need to be studied in controlled randomized trials.
Reactive and proactive control of cognitive functions in obstructive sleep apnea
Authors: Baykal Tulek, Nart Bedin Atalay, Fikret Kanat, Mecit Suerdem
Journal: European Respiratory Journal (2012)

Neuropsychological studies dissociated two types of cognitive control functions: reactive control and proactive control (Braver, T. et al. Trends in Cognitive Sciences 2012; 16: 106-113). Although, obstructive sleep apnea (OSA) is associated with cognitive decrement, there is an ongoing debate on whether these include detrimental performance in conflict tasks (Verstraeten, E. et al. Sleep. 2004; 15;27(4):685-93.). In this study, we investigated reactive and proactive control of cognitive functions in OSA patients.

In this ongoing study data from 21 participants were evaluated. Participants grouped according to Apnea-Hypopnea Index (AHI) in to two, such that Group A's AHI>30 (n=13), and Group B's AHI≤15 (n=8). They were participated in Flanker and Simon to measure reactive control and Stroop to measure proactive control. Stimulus presentation and data collection was done automatically on a standard monitor and PC.

In Group A patients (with severe OSA), reactive control observed with Flanker task was significantly different compared to performance of Group B participants (normal and patients with mild OSA). However, other test did not revealed any significant difference.

View this table:

Comparison of Cognitive Control Performance In Groups





In conclusion, these preliminary results suggested that while proactive control is intact in severe OSA patients, reactive control declines when control is triggered by stimulus-stimulus conflict.
Improved local control and disease-free survival after perioperative chemotherapy for early-stage breast cancer. A European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group Study.
Authors: P C Clahsen, C J van de Velde, J P Julien, J L Floiras, T Delozier, F Y Mignolet, T M Sahmoud
Journal: Journal of Clinical Oncology (1996)

To investigate whether a short intensive course of perioperative polychemotherapy can change the course of early breast cancer.A total of 2,795 women with early breast cancer, stage I to IIIA, were randomized onto a trial (European Organization for Research and Treatment of Cancer [EORTC] 10854) to compare surgery followed by one course of perioperative chemotherapy versus surgery alone. Patients assigned to the chemotherapy arm received one course of fluorouracil 600 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 600 mg/m2 (FAC) intravenously, within 24 hours after surgery. In both randomized treatment arms, a recommendation was made for premenopausal women with positive axillary nodes to receive prolonged courses of cyclophosphamide, methotrexate, and fluorouracil (CMF), according to the standard treatment for this subgroup.At a median follow-up time of 41 months, local control was significantly better in the perioperative treatment arm as compared with the observation arm (hazards ratio, 0.60; 95% confidence interval, 0.44 to 0.83; P < .01). Disease-free survival was significantly prolonged in the chemotherapy arm (hazards ratio, 0.84; 95% confidence interval, 0.70 to 0.99; P = .04). Premenopausal node-negative patients especially showed an advantage for the perioperative chemotherapy arm. No advantage for perioperative chemotherapy was observed in premenopausal node-positive women who also had received prolonged chemotherapy.We conclude that one course of perioperative FAC is able to improve local control and can prolong disease-free survival in women with early breast cancer. However, our results also suggest that a perioperative timing cannot improve the results of standard prolonged chemotherapy in premenopausal women with positive axillary nodes.
Carcinogenicity of Benzo[&lt;italic&gt;a&lt;/italic&gt;]pyrene and Thirteen of Its Derivatives in C3H/fCum Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: R. E. Kouri, A. W. Wood, W. Levin, T. H. Rude, H. Yagi, H. D. Mah, D. M. Jerina, A. H. Conney
Journal: JNCI Journal of the National Cancer Institute (1980)

Benzo[a]pyrene (BP) and 13 of its derivatives were tested for their ability to induce fibrosarcomas in inbred male C3H/fCum mice after a single sc injection. A 0.9-μmol dose of BP in 0.05 ml dimethyl sulfoxide or 0.1 ml trioctanoin produced a 63 or 83% tumor incidence, respectively. At the same dose, benzo[a]pyrene-7,8-oxide had very weak tumorigenic activity whereas the benzo[a]pyrene-4,5-, 9,10-, and 11,12-oxides had no tumorigenic activity. When administered in dimethyl sulfoxide, (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-dihydrodiol) had tumorigenic activity comparable to BP. However, the tumorigenicity of this dihydrodiol was lost when it was injected in trioctanoin. The poor activity of BP-7,8-dihydrodiol relative to BP in trioctanoin may be due, in part, to the polarity of this metabolite because the 7,8-diacetate derivative of BP-7,8-dihydrodiol was 10–15 times more tumorigenic than the dihydrodiol. The lack of tumorigenicity of 7,8-dihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene, a compound lacking the double bond in the 9,10-position but otherwise identical to BP-7,8-dihydrodiol, suggested that the carcinogenicity of the dihydrodiol is mediated by a 7,8-diol-9,10-epoxide of BP. The potent tumorigenicity of 7,8-dihydrobenzo[a]pyrene, compared to that of 9,10-dihydrobenzo[a]pyrene, provided additional evidence for the importance of an intact 9,10-double bond for the metabolic activation of BP. (±)-7β,8α-Dihydroxy-9β,10β-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene had no tumorigenic activity, and its more stable diastereomer, (±)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, induced a fibrosarcoma in only 1 of 18 mice at risk. 2-Hydroxybenzo[a]pyrene, a potent carcinogen on mouse skin and in the newborn mouse, was only 10% as active as BP after sc injection in the mouse.
Prognostic Factors in Children With Localized Malignant Nonseminomatous Germ Cell Tumors
Authors: M. C. Baranzelli, A. Kramar, E. Bouffet, E. Quintana, H. Rubie, C. Edan, C. Patte
Journal: Journal of Clinical Oncology (1999)

Prognostic factors were studied in children older than 1 year who were treated with chemotherapy for extracranial localized malignant non seminomatous germ cell tumors.Data from two consecutive protocols were pooled. The TGM 85 (1985-1989) protocol consisted of alternating courses of cyclophosphamide, dactinomycin and vinblastine, bleomycin, and cisplatin at a dose of 100 mg/m(2) per course. The TGM 90 (1990-1994) protocol was initiated with carboplatin 400 mg/m(2) substituted for cisplatin as the only modification to the previous protocol.We examined alpha-fetoprotein (AFP) levels, disease stage, and primary site and identified three prognostic groups. Patients with a poor prognosis had either an AFP level >/= 10,000 ng/mL or stage III disease and a sacrococcygeal or mediastinal primary site; such patients represented 46% of the patient population and experienced a 43% 3-year failure-free survival rate and a 77% overall survival rate. Patients with a good prognosis had an AFP level less than 10,000 ng/mL, stage I or II disease, and a testicular, ovarian, perineal, or retroperitoneal primary site; such patients represented 22% of the patient population and experienced no treatment failures. The other patients were classified in the intermediate prognosis group and represented 37% of the patient population, with an 81% 3-year failure-free survival rate and a 92% overall survival rate.Initial AFP level, disease stage, and primary site are the most important prognostic factors in this analysis. Prognostic models for pediatric germ cell tumors should allow the stratification of patients for a risk-adapted approach to treatment.
Association of gene expression profile in metastatic melanoma and survival to a dendritic cell-based vaccine
Authors: T. Gajewski, Y. Zha, B. Thurner, G. Schuler
Journal: Journal of Clinical Oncology (2009)

9002 Background: Emerging data suggests that features of the melanoma tumor microenvironment may determine the clinical outcome to immunotherapies. We recently have observed a gene expression signature that correlated with a favorable clinical outcome in response to an IL-12-based melanoma vaccine. Increased expression of chemokine genes and T cell transcripts, and decreased expression of genes associated with aggressive tumor biology, were observed in the favorable group. To determine whether these patterns were reproducible, gene expression profiling was performed from an independent vaccine clinical trial. Methods: Patients with advanced melanoma were treated with autologous, mature monocyte-derived dendritic cells loaded with a combination of melanoma antigen peptides. Pretreatment biopsies were cryopreserved for RNA extraction and gene expression profiling. Patients were categorized into “long survival” (&gt; 24 months) or “short survival” outcomes. Supervised hierarchical clustering was performed to identify genes differentially expressed in the two outcome groups. Results: RNA that passed quality control was obtained from 17 stage IV patients, 5 with a short survival and 12 with a long survival. 408 genes were differentially at least 2- fold. Consistent with previous observations, tumors from favorable outcome patients expressed higher levels of several T cell-specific genes, including Thy1 and CD28; chemokines, including CCL19, CXCL12, and CXCL14; and other immune genes, including LTβ, IL-1R, IFNαR2, IL27R, CD69, and FcRs. Conversely, tumors from unfavorable outcome patients expressed higher levels of pro- angiogeneic genes, including Flt1; anti-apoptotic genes, including SerpinH1 and Serpine1; and multiple collagens. Conclusions: Our results confirm that a subset of transcripts expressed in melanoma metastases may be useful as a predictive biomarker for response to melanoma vaccines. The categories of genes identified point toward new opportunities for overcoming resistance mechanisms. Future studies should integrate gene expression profiling of pre-treatment biopsies as a stratification or enrichment factor in immunotherapy trials. No significant financial relationships to disclose.
The pattern of intrathoracic Hodgkin's disease assessed by computed tomography.
Authors: L F Diehl, K D Hopper, J Giguere, E Granger, M Lesar
Journal: Journal of Clinical Oncology (1991)

Computed tomography (CT) was used to define the sites of intrathoracic abnormality in Hodgkin's disease, determine a pattern of progression of disease in the thorax, and establish the place of this pattern of spread in the differential diagnosis of thoracic abnormalities. One hundred eight patients with newly diagnosed Hodgkin's disease were studied by chest CT. Seventy-seven patients had intrathoracic abnormalities. The pattern seen was one of contiguous spread from the anterior mediastinal/paratracheal area to the other mediastinal lymph node groups (aortopulmonary, subcarinal, posterior mediastinal, and internal mammary), to the hila, and then into the lung by extension or as discrete nodules. Involvement of the pleura, pericardium, or chest wall occurred only after the anterior mediastinal/paratracheal mass had enlarged to greater than 30% of the thoracic diameter. The probability that this pattern of contiguous lymph node spread occurred by chance alone was very small. Hodgkin's disease spreads from the anterior mediastinal/paratracheal area in a contiguous manner. Exceptions are unusual enough that when they occur, diagnoses other than Hodgkin's disease are more likely.
Pain, depression, asthenia, and insomnia: Prevalence of this symptoms cluster and its impact on health-related quality of life in a cohort of advanced cancers
Authors: A. Blasco, A. Galan, D. Almenar, R. Gironés, R. Diaz, V. Alberola
Journal: Journal of Clinical Oncology (2009)

e20607 Background: Pain (P), depression (D), asthenia (A), and insomnia (I), alone or in combination, are some of the most important and invalidating cancer symptoms. But little is known about the relationship between the symptoms of this cluster, and its impact on health-related quality of life (HRQoL). This analysis has been carried out to better know the prevalence of this symptoms cluster and its impact on HRQoL in cancer patients (pts). Methods: An observational and longitudinal multicentre study was carried out on a sample of cancer pts with breast, lung or colon cancer, any site and period of disease duration, receiving chemotherapy. Data were collected at inclusion and 3 months later. Sociodemographic data, key clinical indicators, as well as P, D, A and I complaints or diagnosis were collected. HRQoL was assessed by means of Nottingham Health Profile (NHP) scale (a generic health measure. Analyses were focused on baseline cross-sectional data). Results: A total of 116 pts were analyzed: 73.3 men, 61 years old (SD=9,1), 2.9 years (SD=2,3) since diagnosis, 16.4 % breast, 54.3% lung, and 29.3% colon cancer; 97.4% with metastasis. At least one symptom cluster under study was presented in 69% of pts: &gt;25% a symptom alone, ≈25% two symptoms, &gt;15% three symptoms, &lt;3% all symptoms in the cluster. Pts could be classified in 13 of the 15 symptoms cluster possible combinations (according to their symptoms complaints/diagnosis) ranging from 0.9% to 12.9%. The two symptoms cluster combinations which did not obtain representation included D + I, while the two symptoms cluster combinations more frequents always included pain. It has been observed that a more quantity of symptoms worst physical and psychological NHP scores. Conclusions: The prevalence of the studied symptoms cluster in cancer pts is high (≈70%) and divers in combinations (13 different symptoms profiles). The quantity of prevalent symptoms cluster is clearly associated with HRQoL. [Table: see text] No significant financial relationships to disclose.
Clinical trial of the effect of S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721) (NSC 296961) on the toxicity of cyclophosphamide.
Authors: P V Woolley, M J Ayoob, F P Smith, A Dritschilo
Journal: Journal of Clinical Oncology (1983)

S-2-(3-Aminopropylamino)-ethylphosphorothioic acid (WR-2721) is reported to protect normal tissues from the effects of ionizing radiation and possibly alkylating agents as well. The present trial assessed the ability of this compound to modify the clinical toxicity of cyclophosphamide. Patients with advanced cancer first received a dose of 1000 mg/m2 cyclophosphamide intravenously and were observed for toxicity, principally myelosuppression. After the nadir in white blood cell counts and/or platelets had been documented and adequate recovery had occurred, a second course of cyclophosphamide was given, this time preceded by WR-2721 30 min earlier. In this fashion, each patient served as his own control. Doses of WR-2721 ranging from 250 to 1000 mg/m2 were tested. A total of 13 evaluable courses of WR-2721 were given with cyclophosphamide. In no instance did the prior administration of WR-2721 diminish the bone marrow toxicity of cyclophosphamide alone. At the end of the trial two additional patients received the WR-2721 in a split dose, one-half prior to the cyclophosphamide and one-half 6 hr later; again there was no protection. The side effects of WR-2721 included nausea, vomiting, hypotension, sneezing, and swelling of the tongue. We conclude that WR-2721 is a potentially toxic compound that produces no amelioration of cyclophosphamide toxicity in the doses used. Because of the severity of the side effects of WR-2721, principally hypotension, the trial was terminated after 1000 mg/m2 WR-2721 failed to protect against the toxicity of 1000 mg/m2 cyclophosphamide.
IRE1α/XBP1-mediated branch of the unfolded protein response regulates osteoclastogenesis
Authors: Takahide Tohmonda, Masaki Yoda, Takao Iwawaki, Morio Matsumoto, Masaya Nakamura, Katsuhiko Mikoshiba, Yoshiaki Toyama, Keisuke Horiuchi
Journal: Journal of Clinical Investigation (2015)

The unfolded protein response (UPR) is a cellular adaptive mechanism that is activated in response to the accumulation of unfolded proteins in the endoplasmic reticulum. The inositol-requiring protein-1α/X-box–binding protein–mediated (IRE1α/XBP1-mediated) branch of the UPR is highly conserved and has also been shown to regulate various cell-fate decisions. Herein, we have demonstrated a crucial role for the IREα/XBP1-mediated arm of the UPR in osteoclast differentiation. Using murine models, we found that the conditional abrogation of IRE1α in bone marrow cells increases bone mass as the result of defective osteoclastic bone resorption. In osteoclast precursors, IRE1α was transiently activated during osteoclastogenesis, and suppression of the IRE1α/XBP1 pathway in these cells substantially inhibited the formation of multinucleated osteoclasts in vitro. We determined that XBP1 directly binds the promoter and induces transcription of the gene encoding the master regulator of osteoclastogenesis nuclear factor of activated T cells cytoplasmic 1 (NFATc1). Moreover, activation of IRE1α was partially dependent on Ca2+ oscillation mediated by inositol 1,4,5-trisphosphate receptors 2 and 3 (ITPR2 and ITPR3) in the endoplasmic reticulum, as pharmacological inhibition or deletion of these receptors markedly decreased Xbp1 mRNA processing. The present study thus reveals an intracellular pathway that integrates the UPR and osteoclast differentiation through activation of the IRE1α/XBP1 pathway.
Wallerian Degeneration of the Superior Cerebellar Peduncle
Authors: Thomas Decramer, Philippe Demaerel, Johannes van Loon, Vincent Thijs
Journal: JAMA Neurology (2015)

mg at days 0 and 14).She continued to experience worsening lower extremity weakness.Eventually, she received 6 plasmapheresis treatments with minimal improvement.During the entire period of follow-up at our center, she required 20 to 30 mg daily of oral prednisone.Neurological examination prior to the onset of HiCy therapy revealed symmetrically reduced arm abduction (4-/5) and hip flexion strength (2/5) and her CK level was 2920 U/L.Given progressive muscle weakness in the absence of a robust response to any immunosuppression, she was treated with HiCy, 50 mg/kg per day, for 4 consecutive days and supportive care, as previously described. 2Although she developed neutropenic fever 9 days later, she recovered successfully.She did not require red blood cell or platelet transfusion, and her neutropenia ultimately resolved 2 weeks after HiCy dosing.Muscle strength gradually improved to normal, and her CK level decreased to 537 U/L within 7 months of treatment.A repeated magnetic resonance image was performed 21 months after treatment (Figure ,B).Her steroids were tapered off within 2 years of HiCy therapy.At her last visit, she had minimal residual weakness (4+/5 deltoids and hip flexors), which did not affect her activities of daily living.She has remained in clinical remission while not taking any immunosuppressive therapies, including glucocorticoids, with her most recent CK level normal at 100 U/L 6 years after HiCy treatment.
Adequate locoregional treatment for early breast cancer may prevent secondary dissemination.
Authors: R Arriagada, L E Rutqvist, A Mattsson, A Kramar, S Rotstein
Journal: Journal of Clinical Oncology (1995)

PURPOSE To analyze different events that determine event-free survival (EFS) in a randomized trial on adjuvant radiotherapy in early breast cancer patients with more than 15 years of follow-up evaluation. PATIENTS AND METHODS The trial included 960 patients with a unilateral, operable breast cancer. Surgery consisted of a modified radical mastectomy. The trial compared three arms, as follows: preoperative radiotherapy, postoperative radiotherapy, and no adjuvant treatment. Events were analyzed by a competing-risk approach. A proportional hazards multiple regression model was used to analyze the effects of radiotherapy on the risk of distant metastasis. Similar analyses were performed separately for node-negative [N(-)] and node-positive [N(+)] patients in the two groups that did not include preoperative radiotherapy. RESULTS Radiotherapy produced a fivefold decrease of the risk of local recurrence (P &lt; .0001). In N(+) patients, postoperative radiotherapy decreased the risk of distant dissemination (relative risk, 0.63). When local recurrence was introduced in the model as a time-dependent covariate, this factor was predictive of distant dissemination (P &lt; .0001) and nullified the effect of postoperative radiotherapy. This finding suggests that the decrease of distant metastases was related to the prevention of local recurrence. A similar effect was found in models that used overall survival as an end point. CONCLUSION This study shows that postmastectomy radiotherapy in N(+) breast cancer patients may decrease the distant metastasis rate by preventing local recurrences and thus avoiding secondary dissemination.
The search and destroy strategy prevents spread and long-term carriage of methicillin-resistant Staphylococcus aureus: results from the follow-up screening of a large ST22 (E-MRSA 15) outbreak in Denmark
Authors: S. Böcher, R.L. Skov, M.A. Knudsen, L. Guardabassi, K. Mølbak, P. Schouenborg, M. Sørum, H. Westh
Journal: Clinical Microbiology and Infection (2010)