tbuckley/cabot-search huggingface dataset:
Results of the EICESS-92 Study: Two Randomized Trials of Ewing's Sarcoma Treatment—Cyclophosphamide Compared With Ifosfamide in Standard-Risk Patients and Assessment of Benefit of Etoposide Added to Standard Treatment in High-Risk Patients
Authors: Michael Paulussen, Alan W. Craft, Ian Lewis, Allan Hackshaw, Carolyn Douglas, Jürgen Dunst, Andreas Schuck, Winfried Winkelmann, Gabriele Köhler, Christopher Poremba, Andreas Zoubek, Ruth Ladenstein, Henk van den Berg, Andrea Hunold, Anna Cassoni, David Spooner, Robert Grimer, Jeremy Whelan, Anne McTiernan, Herbert Jürgens
Journal: Journal of Clinical Oncology (2008)

The European Intergroup Cooperative Ewing's Sarcoma Study investigated whether cyclophosphamide has a similar efficacy as ifosfamide in standard-risk (SR) patients and whether the addition of etoposide improves survival in high-risk (HR) patients.SR patients (localized tumors, volume <100 mL) were randomly assigned to receive four courses of vincristine, dactinomycin, ifosfamide, and doxorubicin (VAIA) induction therapy followed by 10 courses of either VAIA or vincristine, dactinomycin, cyclophosphamide, and doxorubicin (VACA; cyclophosphamide replacing ifosfamide). HR patients (volume >or=100 mL or metastases) were randomly assigned to receive 14 courses of either VAIA or VAIA plus etoposide (EVAIA). Outcome measures were event-free survival (EFS; defined as the time to first recurrence, progression, second malignancy, or death) and overall survival (OS).A total of 647 patients were randomly assigned: 79 SR patients were assigned to VAIA, 76 SR patients were assigned to VACA, 240 HR were assigned to VAIA, and 252 HR patients were assigned to EVAIA. The median follow-up was 8.5 years. In the SR group, the hazard ratios (VACA v VAIA) for EFS and OS were 0.91 (95% CI, 0.55 to 1.53) and 1.08 (95% CI, 0.58 to 2.03), respectively. There was a higher incidence of hematologic toxicities in the VACA arm. In the HR group, the EFS and OS hazard ratios (EVAIA v VAIA) indicated a 17% reduction in the risk of an event (95% CI, -35% to 5%; P = .12) and 15% reduction in dying (95% CI, -34% to 10%), respectively. The effect seemed greater among patients without metastases (hazard ratio = 0.79; P = .16) than among those with metastases (hazard ratio = 0.96; P = .84).Cyclophosphamide seemed to have a similar effect on EFS and OS as ifosfamide in SR patients but was associated with increased toxicity. In HR patients, the addition of etoposide seemed to be beneficial.
Abstract LB-163: A phase I trial investigating apoptosis induction with tumor necrosis factor or radiation alone prior to intratumoral injection of autologous dendritic cells in patients with locally advanced or low volume metastatic pancreatic cancer.
Authors: Emmanuel E. Zervos, James J. Mule, Denise Brigham, William Janssen, Jennifer Cooper, Alexander S. Rosemurgy
Journal: Cancer Research (2013)

Abstract The purpose of this trial was to determine the safety, feasibility and efficacy of intra-tumoral injection of an autologous dendritic cell (DC) based vaccine following apoptosis induction with a tumor necrosis factor expressing adenovector (TNF) or low dose radiation therapy (XRT). Methods: Between August 2006 and August 2011, 24 patients with locally advanced (n= 17) or low-volume metastatic (n=7) pancreatic cancer were enrolled to receive either: TNF on day 1 followed by vector activating XRT (2 Gy/d on days 1-3) and then an autologous, KLH pulsed DC vaccine (50M cells, day 4) for 3 weeks; or, XRT (1.9 Gy/d on days1-4) followed by DC vaccine (50M cells, day 5) for 3 weeks. Feasibility endpoints included our ability to produce the vaccine and the subject's ability to complete all phases of the protocol. Serious adverse events (SAE) were recorded to establish safety. Efficacy was established by radiographic and biochemical tumor response, progression free (PFS) and overall survival (OS). Results: All but 2 patients completed the protocol (92%). One patient died prior to initiation of treatment (not included in survival analysis) and one disenrolled during treatment due to deep venous thrombosis. 50 of 66 (76%) total vaccines produced contained greater than 50M DC. There was no vaccine related toxicity. In the TNF group, there were 19 SAEs including one death. In the XRT group, there were 33 SAEs mostly characterized by pain, nausea, dehydration and vomiting. Two (4%) SAEs led to hospital admission, one for duodenal bleeding and one for bacteremia. Tumor response favored the radiation group as did survival. (table) Conclusions: DC based vaccines are feasible and safe in patients with advanced pancreatic cancer. Apoptosis induction using TNF, though less complicated, imparted no survival advantage over radiation alone and may have provided some disadvantage. Efficacy O.S. (mos) P.F.S. (mos) Stable or partial response (%) Stable or decreased Ca19-9(%) TNF (n = 15) 5.8±2.05 4.7±2.17 60 62 XRT (n = 8) 8.7±3.48 6.9±3.79 75 100 Total 6.9±2.92 5.4±2.96 65 76 Citation Format: Emmanuel E. Zervos, James J. Mule, Denise Brigham, William Janssen, Jennifer Cooper, Alexander S. Rosemurgy. A phase I trial investigating apoptosis induction with tumor necrosis factor or radiation alone prior to intratumoral injection of autologous dendritic cells in patients with locally advanced or low volume metastatic pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-163. doi:10.1158/1538-7445.AM2013-LB-163
Placenta growth factor expression is correlated with survival of patients with colorectal cancer
Authors: S-C Wei
Journal: Gut (2005)

<b>Background:</b> Overexpression of vascular endothelial growth factor (VEGF) correlates with vascularity, metastasis, and proliferation in colorectal cancer but the role of its homologue, placenta growth factor (PlGF), is unknown. The aim of this study was to evaluate expression and clinical implications of PlGF in colorectal cancer. <b>Methods:</b> We investigated 74 tumour/non-tumour pairs of colorectal cryosections. Clinical staging was based on the UICC-TNM classification. Expression levels of mRNA for PlGF and VEGF were analysed with quantitative real time reverse transcription-polymerase chain reaction. Proteins were analysed by immunohistochemical staining and enzyme linked immunoabsorbant assay. Analysis of the differences in PlGF and VEGF levels between tumour and non-tumour tissues in the same patient were performed by paired <i>t</i> test; differences between localised and advanced disease patients by the Mann-Whitney, χ<sup>2</sup>, and Fisher’s exact tests and survival curves by the Kaplan-Meier method. <b>Results:</b> Expression levels for both growth factors were significantly higher in tumour than in non-tumour tissues (p⩽0.001). The ratio of PlGF expression in tumour to non-tumour in the advanced disease group was significantly higher than for the localised disease group (p = 0.009). Patients with more tumour PlGF mRNA had shorter survival (p = 0.028). The majority of PlGF was expressed in tumour cells. <b>Conclusions:</b> Our results suggest that PlGF expression correlates with disease progression and patient survival and may be used as a prognostic indicator for colorectal cancer.
Echocardiographically Detected Left Ventricular Hypertrophy: Prevalence and Risk Factors
Authors: DANIEL LEVY
Journal: Annals of Internal Medicine (1988)

The prevalence of and risk factors associated with echocardiographically determined left ventricular hypertrophy were examined in 4976 participants in the Framingham Heart Study (age, 17 to 90 years). Left ventricular hypertrophy was detected in 356 men (16%) and 513 women (19%). Prevalence increases dramatically with age (P < 0.001), with 33% of men and 49% of women age 70 or older affected. A significant association between blood pressure and left ventricular hypertrophy is present and occurs at levels of systolic pressure below 140 mm Hg (age adjusted, P < 0.001). There is a ninefold (women) to tenfold (men) increase from leanest to most obese group (age adjusted, P < 0.001). In multivariate analysis, age, blood pressure, obesity, valve disease, and myocardial infarction are independently associated in both sexes. We conclude that left ventricular hypertrophy is a common echocardiographic finding for which several risk factors can be identified. These findings support weight reduction and blood pressure control for prevention or regression of this condition.
Interactions Between Oncologists and Patients During Rounds
Authors: CHRISTINA G. BLANCHARD
Journal: Annals of Internal Medicine (1983)

Physician behavior during inpatient rounds was observed and quantified for 394 interactions between patients with cancer and physicians. Most patients had solid tumors (90%) and a limited prognosis despite treatment (61%). The physicians spent 1.45 ± 0.58 h on morning rounds seeing an average of 9.3 ± 3.39 patients. For each patient an average of 3.61 ± 2.83 min was spent in the room. The rest of the time was involved in reviewing the results of diagnostic tests, discussing treatment plans, and updating patients' charts. Time spent in the room was significantly related to the patient's sex and diagnosis. Physicians spent more time with patients having the poorest prognosis (p = 0.009). Specific behaviors were analyzed using a Physician Behavior Check List that allows accurate recording of behavior during a brief patient-physician encounter. Factor analysis of responses to the check list resulted in four factors that explained 58.7% of the variance. The physician behavior factor scores failed to correlate with factor scores from the responses of the same physicians to the Cancer Attitude Survey. In addition, the physicians were unable to accurately estimate the time they actually spent with patients or the frequency of specific behaviors that occurred during these interactions.
Vascular Endothelial Growth Factor (VEGF)-A165b Is a Weak <i>In vitro</i> Agonist for VEGF Receptor-2 Due to Lack of Coreceptor Binding and Deficient Regulation of Kinase Activity
Authors: Harukiyo Kawamura, Xiujuan Li, Steven J. Harper, David O. Bates, Lena Claesson-Welsh
Journal: Cancer Research (2008)

Abstract Vascular endothelial growth factor (VEGF)-A165b is a COOH-terminal splice variant of VEGF-A that has been implicated in negative regulation of angiogenesis. We compared the properties of VEGF-A165b with those of VEGF-A121, VEGF-A145, and VEGF-A165. Induction of tyrosine phosphorylation sites in VEGFR-2 differed between the VEGF ligands as determined by tryptic phosphopeptide mapping and by use of phosphosite-specific antibodies. VEGF-A165b was considerably poorer in inducing phosphorylation of the positive regulatory site Y1052 in VEGFR-2. Whereas this did not affect activation of VEGFR-2 in vitro, we show that VEGF-A165b failed to induce vasculogenesis and sprouting angiogenesis in differentiating embryonic stem cells and vascularization of s.c. Matrigel plugs. In addition, the ability of the different VEGF ligands to induce angiogenesis correlated with their abilities to bind the VEGF coreceptor neuropilin 1 (NRP1). Our data indicate that loss of VEGFR-2/NRP1 complex formation and Y1052 phosphorylation contribute to the lack of angiogenic properties of VEGF-A165b. [Cancer Res 2008;68(12):4683–92]
Alkylmercury Contamination of Foods
Authors: Thomas B. Eyl
Journal: JAMA (1971)

No cases of human poisoning by alkylmercury compounds in<i>intended foodstuffs</i>have been reported in North America to date.<sup>1</sup>However, its symptoms are well known, from accidental poisonings and the tragic episodes at Minamata and Niigata, Japan. The chief culprit has been methylmercury. Summarized, these symptoms include, more or less in order of ascending severity, (<i>a</i>) excessive weakness, fatigue, apathy, lack of interest; (<i>b</i>) paresthesias of perioral area and extremities; (<i>c</i>) "tunnel vision," hearing difficulties, fits of rage, depression; (<i>d</i>) dysarthria, dysdiadochokinesia, ataxia, alexia, agraphia, clumsiness in handling familiar objects, intention tremor; (<i>e</i>) gross motor incoordination, spasticity, paralysis, coma, death. Minamata disease, first reported in Japan in 1953, affected 121 persons, causing 46 deaths. Its origin was methylmercury chloride, discharged into the Minamata Bay and River by a plastics plant; fish containing 20
Predictive diagnosis of familial adenomatous polyposis with linked DNA markers: population based study.
Authors: F. MacDonald, D. G. Morton, P. M. Rindl, J. Haydon, R. Cullen, J. Gibson, J. P. Neoptolemos, M. R. Keighley, C. M. McKeown, M. Hulten
Journal: BMJ (1992)

To evaluate the use of polymorphic DNA probes linked to the APC gene in the presymptomatic diagnosis of familial adenomatous polyposis.Four DNA probes were tested on an unselected population of patients at risk of familial adenomatous polyposis.The first 47 families notified to the West Midlands familial adenomatous polyposis register. Plus five families sent to our hospital as part of the West of Britain DNA consortium.The proportion of families and family members in whom DNA testing could be used to adjust the estimate of risk.Only 17 families on the register (containing 46% (74/162) of the population at risk) had a suitable pedigree structure for DNA analysis. DNA was analysed in 12 of these families plus the five families from the West of Britain consortium. At least one probe was informative in 27 of the 33 subjects born with 50% risk, but the most informative probe (pi 227) was the one with the highest recombination rate (10%). Flanking markers were informative in only four of the 33 subjects.These findings confirm the potential for accurate predictive diagnosis of familial adenomatous polyposis with polymorphic DNA probes, but such an approach is currently limited to about one third of affected families. A combined approach to presymptomatic diagnosis, which includes DNA testing and indirect ophthalmoscopy, is advocated.
Metronidazole and anaerobic sepsis.
Authors: S J Eykyn, I Phillips
Journal: BMJ (1976)

Fifty patients with anaerobic sepsis were treated with intravenous and oral metronidazole. In 26 cases this was combined with other antimicrobial agents. Highly satisfactory clinical results were obtained in most patients, though in many surgical drainage was also essential. No side effects or thrombophlebitis were seen. Mixed growths of anaerobic and aerobic bacteria were isolated from all except five patients, who produced only anaerobes. Metronidazole is the only available antimicrobial agent providing selective activity against anaerobic organisms. It is effective and safe and is usually the drug of choice for treating severe anaerobic sepsis.
Postinfectious Cerebellitis: Clinical Significance of Tc-99m HMPAO Brain SPECT Compared With MRI
Authors: ELMER C. SAN PEDRO, JAMES M. MOUNTZ, HONG-GANG LIU, GEORG DEUTSCH
Journal: Clinical Nuclear Medicine (1998)

Purpose: We compared Tc-99m HMPAO brain SPECT and MRI with the clinical findings in a case of a 14-year-old boy with post-infectious cerebellitis. Results: Tc-99m HMPAO brain SPECT scan showed marked reduction in perfusion to the left anterior lobe, left lateral hemisphere, and left posterior lobe of the cerebellum. The MRI showed a limited region of abnormal signal in the mid posterior left cerebellar hemisphere. Since the patient's overall neurological deficit was characterized by ataxia, nystagmus, head and body titubation, dysmetria, dysdiadochokinesia, loss of normal check, and rebound testing attributed to the involvement of the anterior, lateral, and posterior lobes of the left cerebellar hemisphere, the Tc-99m HMPAO brain SPECT finding correlated better with the extent of functional neurological deficits. Conclusion: Tc-99m HMPAO brain SPECT may better assess cerebellar signs and symptoms in cerebellitis since the blood flow abnormalities correlated with dysfunction of the cerebellum, whereas the MRI abnormalities did not encompass the scope of the neurological deficits.
Surgery for Hepatic Neoplasms
Authors: Ronald A. Malt
Journal: New England Journal of Medicine (1985)

LIKE the lungs, the liver is composed of two functionally separate, plethoric, spongy, somewhat fragile organs that are separated by a narrow anatomical plane. Although methods for removing parts of the liver developed far more slowly than those for pulmonary surgery, the risks in both kinds of surgery today depend mainly on the health of the patient and the extent of disease.1 2 3 4 In an otherwise healthy patient, the symptoms, site, size, and spread of a hepatic neoplasm dictate whether an operation should be recommended. Because these criteria can be assessed to an acceptable degree by history taking, physical examination, and . . .
Effectiveness of Team-Managed Home-Based Primary Care&lt;SUBTITLE&gt;A Randomized Multicenter Trial&lt;/SUBTITLE&gt;
Authors: Susan L. Hughes
Journal: JAMA (2000)

Although home-based health care has grown over the past decade, its effectiveness remains controversial. A prior trial of Veterans Affairs (VA) Team-Managed Home-Based Primary Care (TM/HBPC) found favorable outcomes, but the replicability of the model and generalizability of the findings are unknown.To assess the impact of TM/HBPC on functional status, health-related quality of life (HR-QoL), satisfaction with care, and cost of care.Multisite randomized controlled trial conducted from October 1994 to September 1998 in 16 VA medical centers with HBPC programs.A total of 1966 patients with a mean age of 70 years who had 2 or more activities of daily living impairments or a terminal illness, congestive heart failure (CHF), or chronic obstructive pulmonary disease (COPD). Intervention Home-based primary care (n=981), including a primary care manager, 24-hour contact for patients, prior approval of hospital readmissions, and HBPC team participation in discharge planning, vs customary VA and private sector care (n=985).Patient functional status, patient and caregiver HR-QoL and satisfaction, caregiver burden, hospital readmissions, and costs over 12 months.Functional status as assessed by the Barthel Index did not differ for terminal (P=.40) or nonterminal (those with severe disability or who had CHF or COPD) (P=.17) patients by treatment group. Significant improvements were seen in terminal TM/HBPC patients in HR-QoL scales of emotional role function, social function, bodily pain, mental health, vitality, and general health. Team-Managed HBPC nonterminal patients had significant increases of 5 to 10 points in 5 of 6 satisfaction with care scales. The caregivers of terminal patients in the TM/HBPC group improved significantly in HR-QoL measures except for vitality and general health. Caregivers of nonterminal patients improved significantly in QoL measures and reported reduced caregiver burden (P=.008). Team-Managed HBPC patients with severe disability experienced a 22% relative decrease (0.7 readmissions/patient for TM/HBPC group vs 0.9 readmissions/patient for control group) in hospital readmissions (P=.03) at 6 months that was not sustained at 12 months. Total mean per person costs were 6.8% higher in the TM/HBPC group at 6 months ($19190 vs $17971) and 12.1% higher at 12 months ($31401 vs $28008).The TM/HBPC intervention improved most HR-QoL measures among terminally ill patients and satisfaction among non-terminally ill patients. It improved caregiver HR-QoL, satisfaction with care, and caregiver burden and reduced hospital readmissions at 6 months, but it did not substitute for other forms of care. The higher costs of TM/HBPC should be weighed against these benefits.
Congenital Malformations in Pregnancies Complicated by NIDDM: Increased risk from poor maternal metabolic control but not from exposure to sulfonylurea drugs
Authors: Dena Towner, Siri L Kjos, Belinda Leung, Martin M Montoro, Anny Xiang, Jorge H Mestman, Thomas A Buchanan
Journal: Diabetes Care (1995)

OBJECTIVE To determine whether the use of oral hypoglycemic agents during early pregnancy is associated with a risk of congenital malformations in infants of mothers with non-insulin-dependent diabetes mellitus (NIDDM) independent of maternal metabolic control. RESEARCH DESIGN AND METHODS From a prospectively collected data-base of pregnancies complicated by diabetes at a large urban medical center, we identified 332 consecutive infants born to women with NIDDM who did not participate in a preconceptional diabetes care program. Stepwise logistical regression was used to identify maternal characteristics that were independently associated with risks of major and minor congenital malformations in infants. RESULTS Overall, 56 (16.9%) of the 332 infants were born with congenital anomalies (11.7% major anomalies and 5.1% minor anomalies). Analysis of data from subgroups of women who were treated with diet therapy, exogenous insulin, or sulfonylurea compounds during the first 8 weeks of gestation did not reveal statistically significant differences in major or minor malformation rates among the three groups. Stepwise logistic regression analysis revealed two maternal characteristics that were independently associated with major malformations in infants: maternal HbA1c at initial presentation for care (direct relationship; P = 0.0007) and the maternal age at onset of diabetes (inverse relationship; P = 0.009). The risk of major malformations was unrelated to the mode of antidiabetic therapy during early pregnancy. No relationship was found between maternal glycemia or treatment modality and rates of minor congenital anomalies. CONCLUSIONS These data indicate that, in the absence of special preconceptional care, NIDDM is associated with a risk for major congenital anomalies that is in the range reported for pregnancies complicated by insulin-dependent diabetes mellitus. Moreover, the risk in individual patients appears to be related to maternal glycemic control rather than to the mode of antidiabetic therapy during early pregnancy.
Abstract 1357: Inhibition of breast cancer cell growth by a synthetic ligand targeting the nuclear receptor, REV-ERB (NR1D1 and NR1D2)
Authors: Yongjun Wang, Theodore Kamenecka, Douglas Kojetin, Thomas P. Burris
Journal: Cancer Research (2011)

Abstract Disruption of the circadian rhythm leads to increased risk for development of breast cancer in humans. The molecular mechanism underlying the link between circadian rhythm disruption and the increased risk of breast cancer in humans is not clear. The REV-ERBs are nuclear receptors that function as critical regulatory components of the circadian rhythm. We observed that REV-ERBbeta is highly overexpressed in multiple breast cancer cell lines, but not in the non-tumorigenic control breast cell line, MCF-10A. Furthermore, we show that a synthetic REV-ERB agonist that we discovered, SR9011, inhibits the proliferation of multiple breast cancer cell lines including triple negative breast cancers but has no effect on MCF10A cells. We discovered that the REV-ERBs directly regulates the expression of cyclin A2 gene suggesting a possible mechanism for inhibition of proliferation. Treatment of breast cancer cell lines with SR9011 repress the expression of cyclin A2 at both mRNA and protein levels. SR9011 treated SKBR3 cells display a reduced fraction of cells in S phase and in the G2/M phase. Administration SR9011 to synchronized SKBR3 cells results in about 8 hours delay of G2/M phase occurrence. Thus, our data suggests that REV-ERB is a valid target for development of anti-cancer agents and SR9011 holds promise for treatment of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1357. doi:10.1158/1538-7445.AM2011-1357