tbuckley/cabot-search huggingface dataset:
Imaging Intratumoral Convection: Pressure-Dependent Enhancement in Chemotherapeutic Delivery to Solid Tumors
Authors: Terence P.F. Gade, Ian M. Buchanan, Matthew W. Motley, Yousef Mazaheri, William M. Spees, Jason A. Koutcher
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Low–molecular weight (LMW) chemotherapeutics are believed to reach tumors through diffusion across capillary beds as well as membrane transporters. Unexpectedly, the delivery of these agents seems to be augmented by reductions in tumor interstitial fluid pressure, an effect typically associated with high–molecular weight molecules that reach tumors principally through convection. We investigated the hypothesis that improved intratumoral convection can alter tumor metabolism and enhance the delivery of a LMW chemotherapeutic agent to solid tumors. Experimental Design: For this purpose, we applied 31P/19F magnetic resonance spectroscopy (MRS) and magnetic resonance spectroscopic imaging (MRSI) to examine the influence of type I collagenase on tumor bioenergetics and the delivery of 5-fluorouracil (5FU) to HT29 human colorectal tumors grown s.c. in mice. Results: Collagenase effected a 34% reduction in tumor interstitial fluid pressure with an attendant disintegration of intratumoral collagen. Neither mice-administered collagenase nor controls receiving PBS showed changes in 31phosphorus MRS–measured tumor bioenergetics; however, a time-dependent increase in the content of extracellular inorganic phosphate (Pie) was observed in tumors of collagenase-treated animals. 31Phosphorus MRSI showed that this increase underscored a more homogeneous distribution of Pie in tumors of experimental mice. 19Fluorine MRS showed that these changes were associated with a 50% increase in 5FU uptake in tumors of experimental versus control animals; however, this increase resulted in an increase in 5FU catabolites rather than fluoronucleotide intermediates that are required for subsequent cytotoxicity. Conclusions: These data indicate that the modulation of convective flow within tumors can improve the delivery of (LMW) chemotherapeutics and show the potential role for noninvasive imaging of this process in vivo.
Statin Intake Is Associated With Decreased Insulin Sensitivity During Cardiac Surgery
Authors: Hiroaki Sato, George Carvalho, Tamaki Sato, Roupen Hatzakorzian, Ralph Lattermann, Takumi Codere-Maruyama, Takashi Matsukawa, Thomas Schricker
Journal: Diabetes Care (2012)

Surgical trauma impairs intraoperative insulin sensitivity and is associated with postoperative adverse events. Recently, preprocedural statin therapy is recommended for patients with coronary artery disease. However, statin therapy is reported to increase insulin resistance and the risk of new-onset diabetes. Thus, we investigated the association between preoperative statin therapy and intraoperative insulin sensitivity in nondiabetic, dyslipidemic patients undergoing coronary artery bypass grafting.In this prospective, nonrandomized trial, patients taking lipophilic statins were assigned to the statin group and hypercholesterolemic patients not receiving any statins were allocated to the control group. Insulin sensitivity was assessed by the hyperinsulinemic-normoglycemic clamp technique during surgery. The mean, SD of blood glucose, and the coefficient of variation (CV) after surgery were calculated for each patient. The association between statin use and intraoperative insulin sensitivity was tested by multiple regression analysis.We studied 120 patients. In both groups, insulin sensitivity gradually decreased during surgery with values being on average ∼20% lower in the statin than in the control group. In the statin group, the mean blood glucose in the intensive care unit was higher than in the control group (153 ± 20 vs. 140 ± 20 mg/dL; P < 0.001). The oscillation of blood glucose was larger in the statin group (SD, P < 0.001; CV, P = 0.001). Multiple regression analysis showed that statin use was independently associated with intraoperative insulin sensitivity (β = -0.16; P = 0.03).Preoperative use of lipophilic statins is associated with increased insulin resistance during cardiac surgery in nondiabetic, dyslipidemic patients.
A CLASSIFICATION OF THE MURINE LEUKEMIA VIRUSES
Authors: Robert J. Eckner, Richard A. Steeves
Journal: The Journal of Experimental Medicine (1972)

Coinfection of neonatal BALB/c mice with helper-dependent Friend spleen focus-forming virus (SFFV), as contained in the Friend virus (FV) complex, and antigenically distinct Moloney leukemia virus (MolLV) resulted in the recovery of a MolLV pseudotype of SFFV, abbreviated SFFV(MolLV). The antigenic alteration of SFFV was observed by following its neutralization kinetics in vitro by specific Friend or Moloney typing antiserum. Effective pseudotype production was accomplished only when N-tropic LLV-F (the natural helper virus in the FV complex) was inhibited in B-type mice coinfected with an NB-tropic MolLV or other murine leukemia virus (MuLV) preparation. SFFV pseudotypes could not be prepared by using murine viruses other than leukemia viruses. SFFV prepared after two serial passages in the presence of MolLV was effectively neutralized by Moloney antiserum, but not by Friend typing antiserum; therefore, the envelope of the pseudotype virus, SFFV(MolLV), is homogeneous. Pseudotype virus was antigenically stable in the absence of continued mixed infection of BALB/c mice with SFFV(MolLV) and MolLV. However, SFFV(MolLV) was easily converted back to the LLV-F type after only one passage in BALB/c mice coinfected with NB-tropic LLV-F. The antigenic interconversion between LLV-F and MolLV types demonstrated that SFFV is defective with respect to the expression of neutralizable envelope antigens. Analysis of the neutralizable envelope antigens of nine SFFV(MuLV) pseudotypes by a panel of seven typing antisera made possible a "type-specific" SFFV(MuLV) envelope classification. Two major categories have been identified which correspond to the Gross (G) and Friend-Moloney-Rauscher (FMR) subgroups. Further, the FMR subgroup was divided into four types on the basis of distinct neutralization patterns. These results indicated that the specificity observed by cytotoxic G vs. FMR antisera is different from that observed by neutralization kinetics. We therefore suggest that the specific antigens revealed by virus neutralization tests be referred to as type specific.
THE INTERACTION BETWEEN HUMAN MONOCYTES AND RED CELLS
Authors: N. Abramson, E. W. Gelfand, J. H. Jandl, F. S. Rosen
Journal: The Journal of Experimental Medicine (1970)

Studies were carried out in order to characterize the specificity of IgG sub-classes and IgG fragments for rosette formation using red cells and human mononuclear cells. Rosette formation of red cells coated with anti-D was inhibited by free IgG(1) and IgG(3); less inhibition occurred with IgG(2) and IgG(4). Red cells specifically coated with IgG(1) and IgG(3) by chromic chloride were bound to monocytes. Rosette inhibition of anti-D-coated red cells occurred with free Fc fragment of IgG globulin, and only partly with F(ab')(2). Inhibitory capacity of Fc fragments of IgG and gamma(1) heavy chain from heavy chain disease was reversed by the cleavage of disulfide bonds. No inhibition was noted with Fab, or with pepsin components II, III, or IV. These studies indicated that the mononuclear receptor was specific for IgG(1) and IgG(3). The peptide portion of IgG globulin which attached to the mononuclear cell appeared to reside in the N-terminal portion of the Fc fragment and also appeared to require the integrity of the inter-heavy chain disulfide bond. A specific receptor for C3 was not confirmed.
Trends in Diabetes, High Cholesterol, and Hypertension in Chronic Kidney Disease Among U.S. Adults: 1988–1994 to 1999–2004
Authors: Caroline S. Fox, Paul Muntner
Journal: Diabetes Care (2008)

The prevalence of chronic kidney disease (CKD) increased among U.S. adults from 1988-1994 to 1999-2004. We sought to explore the importance of trends in risk factors for CKD over timeThe prevalence of cigarette smoking, obesity, hypertension, high cholesterol, and diabetes among U.S. adults with stage 3 CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m(2)) and albuminuria (urinary albumin-to-creatinine ratio >/=30 mg/g), separately, were determined for 1988-1994 and 1999-2004 using data from serial National Health and Nutrition Examination Surveys. The prevalence ratios (PRs) for stage 3 CKD and albuminuria by the presence of these risk factors were compared across survey periods.The PR for CKD declined between 1988-1994 and 1999-2004 for obesity (PR 1.51 and 1.14 for 1988-1994 and 1999-2004, respectively; P for change = 0.010), hypertension (PR 2.60 and 1.70; P for change = 0.005), and high cholesterol (PR 1.58 and 1.20; P for change = 0.028). However, for diagnosed diabetes, the PR remained unchanged (1.64 and 1.62; P for change = 0.898). Similar results were observed for undiagnosed diabetes (PR of CKD 1.38 and 1.50; P for change = 0.373). The association of cigarette smoking was similar in each time period. Besides obesity, for which the association remained stable over time, similar patterns were observed for the PR of albuminuria.In terms of CKD, improvements in hypertension and high cholesterol management have been offset by both diagnosed and undiagnosed diabetes. Further increases in CKD may occur if diabetes continues to increase.
Defining discriminative pain trajectories in hip osteoarthritis over a 2-year time period
Authors: Saskia P J Verkleij, Trynke Hoekstra, Rianne M Rozendaal, Jan H Waarsing, Bart W Koes, Pim A J Luijsterburg, Sita M A Bierma-Zeinstra
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Although pain due to osteoarthritis (OA) generally deteriorates over time, there is a large individual variation in the course of pain. This study examines the different longitudinal trajectories of patients with hip pain due to OA. <h3>Methods</h3> Data from a previously performed randomised controlled trial were used to investigate the course of pain over 2 years in 222 patients with clinically and radiographically determined hip OA. Pain was measured with a visual analogue scale (0–100). Latent class growth analysis was used to determine the number of trajectories of patients with hip pain due to OA. <h3>Results</h3> Analyses yielded five trajectories of pain due to hip OA. Trajectory 1 ('mild pain'; n=69) consists of patients with stable mild pain. Patients in trajectory 2 ('moderate pain'; n=31) fluctuated slightly between moderate and severe pain levels. Trajectory 3 ('always pain'; n=32) consists of patients with severe pain. Patients in trajectory 4 ('regularly progressing'; n=48) started with mild pain and progressed slowly to moderate pain. Trajectory 5 ('highly progressing'; n=42) patients also started with mild pain but quickly progressed to severe pain over 2 years. Compared with the 'mild pain' group, patients in the 'always pain' group had more severe radiographic hip OA, morning stiffness and decreased range of motion. The 'highly progressing' group had more severe radiographic hip OA and morning stiffness. <h3>Conclusions</h3> Latent class growth analysis applied to longitudinal data of patients with hip OA identified five distinct trajectories of pain. More studies are needed to externally validate these findings.
Functional Neuroimaging Evidence for Hyperarousal in Insomnia
Authors: Eric A Nofzinger, Daniel J Buysse, Anne Germain, Julie C Price, Jean M Miewald, David J Kupfer
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The authors investigated the neurobiological basis of poor sleep and daytime fatigue in insomnia. METHOD: [18F]Fluorodeoxyglucose positron emission tomography was used to assess regional cerebral glucose metabolism of seven patients with insomnia and 20 healthy subjects. RESULTS: Compared with healthy subjects, patients with insomnia showed greater global cerebral glucose metabolism during sleep and while awake, a smaller decline in relative metabolism from waking to sleep states in wake-promoting regions, and reduced relative metabolism in the prefrontal cortex while awake. CONCLUSIONS: Subjectively disturbed sleep in patients with insomnia is associated with greater brain metabolism. The inability to fall asleep may be related to a failure of arousal mechanisms to decline in activity from waking to sleep states. Further, daytime fatigue may reflect decreased activity in the prefrontal cortex resulting from inefficient sleep.
Recurrent and Chronic Spontaneous Pneumothorax
Authors: R. C. Brock
Journal: Thorax (1948)

PLATE'XXV.-(a)Radiograph frcm a case of recurrent, alternating pneumothorax in a young man. (b) Right broncho- gram of the same patient as in (a); shrunken, atelactatic and bronchiectatic middle and lower lobes are revealed.(c) Thoracoscopic view of a large bulla to show a perforation.
SPSB1 Promotes Breast Cancer Recurrence by Potentiating c-MET Signaling
Authors: Yi Feng, Tien-Chi Pan, Dhruv K. Pant, Kristi R. Chakrabarti, James V. Alvarez, Jason R. Ruth, Lewis A. Chodosh
Journal: Cancer Discovery (2014)

Breast cancer mortality is principally due to tumor recurrence; however, the molecular mechanisms underlying this process are poorly understood. We now demonstrate that the suppressor of cytokine signaling protein SPSB1 is spontaneously upregulated during mammary tumor recurrence and is both necessary and sufficient to promote tumor recurrence in genetically engineered mouse models. The recurrence-promoting effects of SPSB1 result from its ability to protect cells from apoptosis induced by HER2/neu pathway inhibition or chemotherapy. This, in turn, is attributable to SPSB1 potentiation of c-MET signaling, such that preexisting SPSB1-overexpressing tumor cells are selected for following HER2/neu downregulation. Consistent with this, SPSB1 expression is positively correlated with c-MET activity in human breast cancers and with an increased risk of relapse in patients with breast cancer in a manner that is dependent upon c-MET activity. Our findings define a novel pathway that contributes to breast cancer recurrence and provide the first evidence implicating SPSB proteins in cancer.The principal cause of death from breast cancer is recurrence. This study identifies SPSB1 as a critical mediator of breast cancer recurrence, suggests activation of the SPSB1-c-MET pathway as an important mechanism of therapeutic resistance in breast cancers, and emphasizes that pharmacologic targets for recurrence may be unique to this stage of tumor progression.
Prospective Analysis of Hepatitis B Virus Reactivation in Patients With Diffuse Large B-Cell Lymphoma After Rituximab Combination Chemotherapy
Authors: Nozomi Niitsu, Yuki Hagiwara, Ken Tanae, Mika Kohri, Naoki Takahashi
Journal: Journal of Clinical Oncology (2010)

Purpose Recently, there have been reports of hepatitis B virus (HBV) reactivation after rituximab combination chemotherapy in hepatitis B surface antigen (HBsAg) –negative patients with B-cell lymphoma. In this prospective study, the frequency of and risk factors for HBV reactivation in patients who were receiving rituximab chemotherapy were examined. Patients and Methods A total of 314 HBsAg-negative patients with diffuse large B-cell lymphoma were treated with rituximab chemotherapy. Antibody to hepatitis B surface antigen (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) tests were performed in all patients. In patients who were positive for anti-HBs and/or anti-HBc, serum HBV-DNA was measured. Results Of the 314 patients, 51 (16.2%) were HBV carriers. HBV reactivation occurred during or after rituximab chemotherapy in six patients (12%). All six patients who developed HBV reactivation were anti-HBc positive, and three of them were also anti-HBs positive. In these six patients, the pretreatment anti-HBs titer was low. Entecavir administration was started when serum HBV DNA became positive, and serum HBV-DNA became negative within 1 to 3 weeks. Rituximab chemotherapy was then continued. Risk factors for HBV reactivation were being male and having a low anti-HBs titer. Conclusion HBV reactivation occurred in some patients who had been anti-HBs negative or had a low anti-HBs level. In addition, HBV reactivation occurred at an early stage of rituximab chemotherapy, but rituximab chemotherapy could be continued after entecavir administration reduced the serum HBV-DNA level. Entecavir (BMS 200495) prophylaxis was not performed when rituximab chemotherapy was started, and it was thought that entecavir could be started when serum HBV-DNA increased.
Early Responses to Chemotherapy of Normal and Malignant Hematologic Cells Are Prognostic in Children With Acute Lymphoblastic Leukemia
Authors: Stephen J. Laughton, Lesley J. Ashton, Edward Kwan, Murray D. Norris, Michelle Haber, Glenn M. Marshall
Journal: Journal of Clinical Oncology (2005)

Improved cure rates for children with acute lymphoblastic leukemia (ALL) have resulted from better relapse prediction, using clinical and laboratory features at diagnosis, and more intensive therapy in high-risk patients. More recently, measurements of the variation in the response of malignant lymphoblasts to chemotherapy in vivo have further improved relapse prediction. It is unknown whether the variation in the response of nonmalignant hematologic cells after chemotherapy correlates with the response of lymphoblasts or risk of relapse.We retrospectively evaluated myelosuppression during induction and consolidation chemotherapy in 227 children uniformly treated for ALL on consecutive Australian and New Zealand Children's Cancer Study Group protocols. The early response to treatment was assessed in a representative subset (n = 62) by determining minimal residual disease (MRD) level by molecular techniques on the end-of-induction bone marrow sample.We found that a slow rate of myeloid recovery at the end of induction chemotherapy, reflected in a low absolute neutrophil count (ANC), was highly predictive of relapse (P < .0001). Additionally, patients with a high end-of-induction MRD level had a high risk of relapse (P = .001). Multivariate analysis confirmed the independent prognostic significance of MRD and ANC at the end of induction chemotherapy (P < .05). There was no significant association between other measures of myelotoxicity and MRD or relapse.We conclude that the responses of normal myeloid cells and malignant lymphoblasts to chemotherapy predict outcome by distinct mechanisms. While these results are promising, their use in the clinical setting needs to be examined in a future randomized controlled trial.
Targeting mTOR dependency in pancreatic cancer
Authors: Douglas C Morran, Jianmin Wu, Nigel B Jamieson, Agata Mrowinska, Gabriela Kalna, Saadia A Karim, Amy Y M Au, Christopher J Scarlett, David K Chang, Malgorzata Z Pajak, Karin A Oien, Colin J McKay, C Ross Carter, Gerry Gillen, Sue Champion, Sally L Pimlott, Kurt I Anderson, T R Jeffry Evans, Sean M Grimmond, Andrew V Biankin, Owen J Sansom, Jennifer P Morton
Journal: Gut (2014)

<h3>Objective</h3> Pancreatic cancer is a leading cause of cancer-related death in the Western world. Current chemotherapy regimens have modest survival benefit. Thus, novel, effective therapies are required for treatment of this disease. <h3>Design</h3> Activating <i>KRAS</i> mutation almost always drives pancreatic tumour initiation, however, deregulation of other potentially druggable pathways promotes tumour progression. PTEN loss leads to acceleration of <i>Kras<sup>G12D</sup></i>-driven pancreatic ductal adenocarcinoma (PDAC) in mice and these tumours have high levels of mammalian target of rapamycin (mTOR) signalling. To test whether these KRAS PTEN pancreatic tumours show mTOR dependence, we compared response to mTOR inhibition in this model, to the response in another established model of pancreatic cancer, KRAS P53. We also assessed whether there was a subset of pancreatic cancer patients who may respond to mTOR inhibition. <h3>Results</h3> We found that tumours in KRAS PTEN mice exhibit a remarkable dependence on mTOR signalling. In these tumours, mTOR inhibition leads to proliferative arrest and even tumour regression. Further, we could measure response using clinically applicable positron emission tomography imaging. Importantly, pancreatic tumours driven by activated KRAS and mutant p53 did not respond to treatment. In human tumours, approximately 20% of cases demonstrated low PTEN expression and a gene expression signature that overlaps with murine KRAS PTEN tumours. <h3>Conclusions</h3> KRAS PTEN tumours are uniquely responsive to mTOR inhibition. Targeted anti-mTOR therapies may offer clinical benefit in subsets of human PDAC selected based on genotype, that are dependent on mTOR signalling. Thus, the genetic signatures of human tumours could be used to direct pancreatic cancer treatment in the future.
Molecular processes that handle — and mishandle — dietary lipids
Authors: Kevin Jon Williams
Journal: Journal of Clinical Investigation (2008)

Overconsumption of lipid-rich diets, in conjunction with physical inactivity, disables and kills staggering numbers of people worldwide. Recent advances in our molecular understanding of cholesterol and triglyceride transport from the small intestine to the rest of the body provide a detailed picture of the fed/fasted and active/sedentary states. Key surprises include the unexpected nature of many pivotal molecular mediators, as well as their dysregulation — but possible reversibility — in obesity, diabetes, inactivity, and related conditions. These mechanistic insights provide new opportunities to correct dyslipoproteinemia, accelerated atherosclerosis, insulin resistance, and other deadly sequelae of overnutrition and underexertion.
Resource implications of palliative chemotherapy for ovarian cancer.
Authors: C Doyle, M Stockler, M Pintilie, P Panesar, P Warde, J Sturgeon, A M Oza
Journal: Journal of Clinical Oncology (1997)

To describe the costs and outcomes of palliative chemotherapy in women with recurrent and refractory ovarian cancer from the perspective of a health care provider.A retrospective study of 40 consecutive women who started second- or third-line chemotherapy for recurrent or refractory ovarian cancer between 1989 and 1992. Resource utilization from the commencement of second- or third-line chemotherapy until death or last follow-up evaluation was determined from a detailed chart review. All elements of care were recorded, including inpatient admissions, outpatient visits, chemotherapy drugs, nonchemotherapy drugs, radiation therapy, surgical procedures, investigations, and home care. Costs calculated using the hotel-approximation method are expressed in 1994 Canadian dollars. Actuarial estimates of cost and survival were used to account for censored observations.After a minimum follow-up period of 24 months, 36 of 40 women had died. The median survival duration of the group was 1.1 years from study entry and 1.7 years from first relapse. The women received a median of two regimens of chemotherapy (range, one to four) from study entry. They spent a median of 33 days as hospital inpatients (mean, 46; range, 0 to 185); 58% of these inpatient days were for symptomatic management and 32% were for chemotherapy. The mean cost per patient was $53,000 (median, $36,600; range, $4,800 to $162,900). The relationship between cost and survival duration was not linear--the cost per year was lowest for those who lived longest. Inpatient admissions, chemotherapy drugs, and outpatient visits accounted for 62%, 21%, and 8% of the total cost, respectively. The total costs attributable to chemotherapy were $24,000 (45% of total costs) and the total costs attributable to supportive care were $23,000 (43% of total costs).These data illustrate the cost of palliative management of recurrent and refractory ovarian cancer, which must be considered in the context of quality and duration of survival. They indicate the potential to improve cost efficiency by improving resource management, for example, by shifting from inpatient to outpatient chemotherapy, everything else being equal.