tbuckley/cabot-search huggingface dataset:
Evaluation of risk factors associated with denosumab induced hypocalcemia.
Authors: Sergio Alberto Trevino Manllo, Pushpinderdeep Khalon, Ravneet Thind, Roma Bhatia, Haythem Y. Ali
Journal: Journal of Clinical Oncology (2014)

144 Background: Denosumab is a monoclonal antibody that neutralizes RANKL preventing osteoclast activation. It has been shown to be superior to zoledronic acid in preventing skeletal-related events in breast cancer with bone metastases. Hypocalcemia has been reported as a common side effect. The aim is to evaluate the risk factors associated with denosumab induce hypocalcemia. Methods: Retrospective study in which 144 charts were reviewed. Baseline characteristics: age, gender, race, type of cancer, calcium, phosphate, vitamin D, PTH, creatinine levels, GFR and corrected calcium were obtained. Tumors were classified in hormone sensitive versus non-sensitive. Charts were reviewed to evaluate for the development and severity of hypocalcemia as defined by the international review criteria. A multivariant analysis to evaluate the relationship between hypocalcemia and the variables of interest was done. Results: Hypocalcemia was observed in 71 of 144 patients. Grade 2 hypocalcemia was the most common. Significantly lower levels of GFR at baseline were detected in patients withhypocalcemia. Hormone responsive tumors were significantly less likely to develop hypocalcemia. Conclusions: Despite adequate supplementation of vitamin D and calcium, hypocalcemia is a common side effect of Denosumab. Careful monitoring of calcium levels is necessary especially in chronic kidney disease and hormone insensitive tumors. [Table: see text]
First-Year Visual Acuity Outcomes of Providing Aflibercept According to the VIEW Study Protocol for Age-Related Macular Degeneration
Authors: James S. Talks, Andrew J. Lotery, Faruque Ghanchi, Sobha Sivaprasad, Robert L. Johnston, Nishal Patel, Martin McKibbin, Clare Bailey, Sajjad Mahmood, Aires Lobo, Bobby Paul, Qureshi Kashif, Cynthia Santiago, Gavin Walters, Mohamed Tahir, Bushra Mushtaq
Journal: Ophthalmology (2015)
A randomized controlled pilot of home-based exercise (HBEX) versus standard care (SC) among breast (BC) and prostate cancer (PC) patients receiving radiation therapy (RTH)
Authors: K. M. Mustian, G. R. Morrow, J. Yates, L. Gillies, C. Boles
Journal: Journal of Clinical Oncology (2006)

8504 Background: Cancer-related fatigue (CRF) is reported in up to 97% of cancer patients during RTH. 60% rate it as moderate to severe. Fatigue can significantly reduce functional capacity (FC), treatment compliance, and QOL. Although there is no standard treatment for CRF, aerobic exercise has demonstrated a positive influence on CRF and FC during RTH, but the influence of combined resistance and aerobic exercise is not clear. We explored the efficacy of a low to moderate home-based exercise intervention, including resistance and aerobic training, to SC on CRF and domains of FC (aerobic capacity and strength), in a sample of BC and PC patients during RTH. Methods: BC and PC patients (N=38; ξ age=56; 71% BC), beginning at least 28 sessions of RTH were randomized to a 4wk HBEX (7 days/wk) or SC condition, with CRF (FACT subscale), aerobic capacity (6-min. walk), and strength (handgrip dynamometry) assessments pre and post-intervention. Results: Change scores indicated improvements in the HBEX group (N=19) in CRF (ξ=3.6, SE=2.1) and aerobic capacity (ξ=43.6, SE=52.3), while the SC group declined in CRF (ξ=-1.1, SE=1.1) and aerobic capacity (ξ=-28.5 SE=71.6). Change scores revealed declines in strength among both groups, however the HBEX group showed smaller declines in strength (ξ=-.05, SE=0.7) compared to the SC group (ξ=-.80, SE=.91). T-tests using intent-to-treat indicated statistically significant between group differences on changes in CRF (ES=.63; p=.05) from pre to post-intervention, as well as significantly higher aerobic capacity (ES=1.3; p&lt;.001) with a statistical trend toward lower CRF (ES=.51; p=.09) between groups post-intervention. Conclusions: HBEX improved CRF and aerobic capacity, while SC resulted in declines. HBEX reduced declines in strength compared to SC. Future phase III randomized controlled trials are needed with larger samples to fully investigate the influence of this HBEX intervention on CRF, aerobic capacity and strength. Funded by NCI grant 1R25CA102618. No significant financial relationships to disclose.
Telehealthcare for patients with COPD, effects on physical activity level, physical capacity and dyspnea: A systematic review and meta-analysis
Authors: Sara Lundell, Åsa Holmner, Börje Rehn, Andre Nyberg, Karin Wadell
Journal: European Respiratory Journal (2014)

Only a minority of patients with chronic obstructive pulmonary disease (COPD) have access to pulmonary rehabilitation (PR). Home-based solutions, e.g. telehealthcare, have been used in efforts to make PR more available.   Aim:  To investigate the effects of telehealthcare on physical activity level, physical capacity and dyspnea in patients with COPD, and to describe the interventions.   Methods:  Studies were identified through database searches, reference lists and contacts with included authors. Abstracts and articles were reviewed based on eligibility criteria by three authors. Risk of bias was individually assessed by two authors. Standardized mean differences (SMD) with 95% CI were calculated. Forest plots were used to present data visually.   Results:  Eleven studies (ten RCT) with a total of 1051 patients were included. Regular phone calls was the most common intervention. Rehabilitation promoted through websites or mobile phones was also used. Telehealthcare was often combined with education and/or exercise training. Comparators were ordinary care, exercise training and/or education. For dyspnea there was a small significant effect favoring telehealthcare (SMD, 0.147; 95% CI, 0.015-0.279). For physical activity level (SMD, 0.328; 95% CI, -0.053-0.709) and physical capacity (SMD, 0.147; 95% CI, -0.094-0.387) a positive trend favoring telehealthcare, although not significant, was found.   Conclusions:  The use of telehealthcare can lead to improvements in dyspnea and seems to be promising also for improving physical activity level and physical capacity. More studies with the aim to evaluate telehealthcare as main intervention would be of benefit.
Effect of hyperthermia on the pharmacokinetic profile of oxaliplatin administered by intraperitoneal route in rats
Authors: N. Piche, F. Leblond, L. Sideris, G. Leblanc, Y. E. Leclerc, V. Pichet, P. Dube
Journal: Journal of Clinical Oncology (2007)

14535 Background: Whereas in vitro studies have demonstrated that hyperthermia enhances the cytotoxicity and tissue penetration of oxaliplatin, in vivo studies conducted so far have failed to document clearly such effect in the context of heated intraperitoneal chemotherapy. The purpose of this study is to assess the effect of heat on the pharmacokinetic profile of oxaliplatin administered intraperitonealy in rats. Methods: Under general anesthesia, 25 Sprague-Dawly rats of 258 g (235–440 g) were submitted to 3 different doses of intraperitoneal oxaliplatin (460, 920 and 1840 mg/m2) at 3 different temperatures of perfusion (37, 40 and 43Â°C) during 25 minutes. At the end of perfusion, samples in different compartments were harvested for dosage of oxaliplatin concentration: 2 ml of perfusate, 1 ml of portal blood, 1 ml of systemic blood, 100 mm3 of parietal peritoneum and 100 mm3 of mesentery. Dosage of oxaliplatin was performed by high performance liquid chromatography. Results: We observed a linear and proportional correlation between the concentration of oxaliplatin in the perfusate and the concentration of oxaliplatin for all compartments (R2 : 0.9833 for systemic blood, 0.9874 for portal blood, 0.9053 for parietal peritoneum and 0.9999 for mesentery). Regarding the effect of temperature, we observed a linear and proportional correlation of heat on the concentration of oxaliplatin in parietal peritoneum (R2 : 0.8543), no effect on mesentery (R2: 0.1371) and a tendency of heat to limit concentration of oxaliplatin in portal and systemic blood (R2 = 0.0994 and 0.5854 respectively). Conclusion: Heat improves the absorption of oxaliplatin into the peritoneal cells and seems to limit the systemic absorption of oxaliplatin, the latter observation suggesting a decrease in systemic toxicity. These are two strong arguments supporting the use of oxaliplatin by intraperitoneal route, as it is currently done in the human treatment of peritoneal carcinomatosis from colorectal origin. No significant financial relationships to disclose.
Inhibitory Effect of Medroxyprogesterone Acetate on Foreign Body Tumorigenesis in Mice
Authors: C Lanari, A A Molinolo, C D Pasqualini
Journal: JNCI Journal of the National Cancer Institute (1986)

This paper reports on the investigation of the effect of medroxyprogesterone acetate (MPA) on foreign body tumorigenesis that resulted from sc implantation of a glass cylinder. Adult BALB/c mice of both sexes bearing the foreign body were separated into groups. Group 1 received 40 mg MPA sc every 2 months during 1 year, in the vicinity of the glass cylinder; group 2 received the same MPA treatment in the contralateral flank; and group 3 received no hormonal treatment. Sarcomas developed in 4 of 39, 9 of 41, and 17 of 39 mice, respectively. With the use of an evaluation based on the number of high-risk mice per time interval, the MPA inhibitory effect was found to be statistically significant in both groups: 26, 53, and 79% tumor incidence, respectively. A decrease in the rate of tumor development also was observed but only in mice treated with MPA in situ. An unexpected side effect of continuous MPA administration in females was the appearance of adenocarcinomas.
Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes
Authors: G Garcia-Manero, S D Gore, S Kambhampati, B Scott, A Tefferi, C R Cogle, W J Edenfield, J Hetzer, K Kumar, E Laille, T Shi, K J MacBeth, B Skikne
Journal: Leukemia (2015)

CC-486, the oral formulation of azacitidine (AZA), is an epigenetic modifier and DNA methyltransferase inhibitor in clinical development for treatment of hematologic malignancies. CC-486 administered for 7 days per 28-day treatment cycle was evaluated in a phase 1 dose-finding study. AZA has a short plasma half-life and DNA incorporation is S-phase-restricted; extending CC-486 exposure may increase the number of AZA-affected diseased target cells and maximize therapeutic effects. Patients with lower-risk myelodysplastic syndromes (MDS) received 300 mg CC-486 once daily for 14 days (n=28) or 21 days (n=27) of repeated 28-day cycles. Median patient age was 72 years (range 31–87) and 75% of patients had International Prognostic Scoring System Intermediate-1 risk MDS. Median number of CC-486 treatment cycles was 7 (range 2–24) for the 14-day dosing schedule and 6 (1–24) for the 21-day schedule. Overall response (complete or partial remission, red blood cell (RBC) or platelet transfusion independence (TI), or hematologic improvement) (International Working Group 2006) was attained by 36% of patients receiving 14-day dosing and 41% receiving 21-day dosing. RBC TI rates were similar with both dosing schedules (31% and 38%, respectively). CC-486 was generally well-tolerated. Extended dosing schedules of oral CC-486 may provide effective long-term treatment for patients with lower-risk MDS.
Including variability as a criteria, increases diagnostic accuracy in elite asthmatic swimmers after mannitol and exercise challenge
Authors: Kerstin Romberg, Ellen Tufvesson, Leif Bjermer
Journal: European Respiratory Journal (2011)

Increased frequency of asthma has been reported among swimmers, but many tests have a low sensitivity to detect asthma among elite athletes. The

Aim was to investigate the prevalence of asthma among elite swimmers, to compare sport specific exercise test with Mannitol and explore the tests ability to detect asthma.

Methods: 101 elite swimmers (14-24 years) performed both Mannitol provocation and a sport specific exercise test. Mannitol positivity was defined as either direct FEV1 PD15 or as β2- reversibility ≥ 15% after challenge (=extended criteria). A direct positive exercise test was defined as a drop in FEV1 of 10% compared to baseline or a difference in FEV of >15% either spontaneous, variability or with β2-agonist, reversibility (=extended criteria).

Results: We found a high prevalence of Mannitol and/or Exercise positivity. For Mannitol, 26 were positive by ordinary criteria and 43 with extended criteria. The corresponding numbers for exercise test were 14 and 24. When including reversibility and variability to define a positive test the sensitivity to detect current asthma with or without exercise induced symptoms increased while the specificity remained unchanged. Direct positivity for Mannitol or Exercise poorly overlapped using ordinary criteria. The conformity was better using the extended criteria.

Conclusion: We found a high prevalence of EIA among elite swimmers. The use of variability and reversibility as additional criteria to define a positive test increased the ability to detect asthma with or without exercise induced symptoms, without lowering the specificity, and should therefore be considered in the interpretation of the tests.
Aromatase inhibitor therapy for estrogen receptor positive ovarian cancer
Authors: N. S. Tchekmedyian, A. K. Liem, E. T. Quan, D. M. Burtzo, K. Ucar
Journal: Journal of Clinical Oncology (2006)

15038 Background: Aromatase inhibitors (AI) are effective therapy for estrogen receptor positive breast cancer. We retrospectively reviewed our experience with AI therapy of 14 advanced ovarian cancer patients. Methods: Between March 2001 and January 2006, 14 women with ages ranging from 40 to 80 years received letrozole 2.5 mg orally once a day for periods of 2 to 36 months. All 14 patients had received prior chemotherapy and had recurrent disease. Eleven had received a mean of 2.8 (range 1–7) different chemotherapy regimens for advanced recurrent disease. Six of the 14 patients had received tamoxifen for periods of 1 to 12 months. Thirteen patients had advanced recurrent invasive epithelial ovarian cancer. One patient had advanced progressive ovarian tumor of borderline malignant potential with pleural involvement refractory to chemotherapy. Estrogen receptor status was positive in 13 patients and unknown in 1. CA-125 levels and clinical evaluations were available for all patients. Results: The mean baseline CA-125 level (U/mL) prior to letrozole therapy was 262, and ranged from 4.1 to 2723. The mean lowest CA-125 level after letrozole was started was 143, and ranged from 1.3 to 1158. Five of the 14 patients had CA-125 declines of ≥50% while on letrozole. Seven of the 14 patients remain on therapy at 2+ to 20+ months. Ten of the 14 patients had sustained clinical improvements or stability and no evidence of disease progression while on AI therapy for a mean period of 12 months with a range of 2 to 36 months. AI therapy was well tolerated. Conclusion: This limited and anecdotal experience suggests that AI therapy may be effective in advanced estrogen receptor positive ovarian cancer, including patients refractory to chemotherapy. AI therapy should be studied further in advanced ovarian cancer and in the adjuvant setting. No significant financial relationships to disclose.
Abstract 026: Optical Recording of Cardiac Action Potentials from Human Induced Pluripotent Stem Cell Derived Cardiomyocytes
Authors: B Alexander Yi, Joel M Kralj, Adam E Cohen
Journal: Circulation Research (2013)

The electrically excitable properties of cardiomyocytes stem from the activity of ion channels that allow the coordinated entry of ions to generate cardiac action potentials. Disruptions in ion channel function either by drugs or gene mutations can lead to cardiac arrhythmias. The ability to screen drugs or gene mutations rapidly for effects on the cardiac action potential would be of interest for both drug discovery as well as for studies of ion channel function; however, the time-consuming and technically challenging nature of conventional patch clamping can limit the ability to perform high throughput screens. Archaerhodopsin3, or Arch, is an Archaebacterial variant of the membrane protein bacteriorhodopsin that binds a retinal fluorophore whose signal is rapidly responsive to changes in membrane potential. Here, we report the use of Arch to optically record action potentials from human induced pluripotent stem cell-derived cardiomyocytes. Human induced pluripotent stem cells that stably express Arch were generated and then differentiated into cardiomyocytes. As compared to patch clamping, Arch faithfully reproduces many of the key features of cardiac action potentials and may be a tool to be used for high throughput electrophysiological screens of cardiomyocytes.
Associations Between Community Income and Cancer Survival in Ontario, Canada, and the United States
Authors: Chris Boyd, Jina Y. Zhang-Salomons, Patti A. Groome, William J. Mackillop
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The objectives of this study were as follows: (1) to compare the magnitude of the association between socioeconomic status (SES) and cancer survival in the Canadian province of Ontario with that in the United States (U.S.), and (2) to compare cancer survival in communities with similar SES in Ontario and in the U.S. METHODS: The Ontario Cancer Registry provided information about all cases of invasive cancer diagnosed in Ontario from 1987 to 1992, and the Surveillance, Epidemiology and End Results Registry (SEER) provided information about all cases diagnosed in the SEER regions of the U.S. during the same time period. Census data provided information about SES at the community level. The product-limit method was used to describe cause-specific survival. Cox proportional hazards models were used to describe the association between SES and the risk of death from cancer. RESULTS: There were significant associations between SES and survival for most cancer sites in both the U.S. and Ontario, but the magnitude of the association was usually larger in the U.S. In the poorest communities, there were significant survival advantages in favor of cancer patients in Ontario for many disease groups, including cancers of the lung, head and neck region, cervix, and uterus. However, in upper- and middle-income communities, there were significant survival advantages in favor of the U.S. for all cases combined and for several individual diseases, including cancers of the breast, colon and rectum, prostate, and bladder. CONCLUSION: The association between SES and cancer survival is weaker in Ontario than it is in the U.S. This is due to a combination of better survival among patients in the poorest communities and worse survival among patients in the wealthier communities of Ontario relative to those in the U.S.
Pathobiologic Nature of Lymphocyte Interactions With Human Breast Cancer&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Russell P. Sherwin, Arnis Richters
Journal: JNCI Journal of the National Cancer Institute (1972)

From a study of 53 human breast cancers in tissue culture, a number of lymphocyte interactions with cancer and non-neoplastic cells have been defined and categorized to include random migratory and ameboid activities and special interactions of polesis, peripolesis, pedopolesis, clumping, clustering, congregation, emperipolesis, and mechanoclasmatosis. Also noted were lymphocyte trapping on the surface and within the interior of target cells, lymphocyte degeneration and inclusion body formation, lymphocyte escape, a tendency to Golgi zone localization, vacuole-associated emperipolesis, and “pointing” as the initiating step in emperipolesis. The use of short-term autochthonous tissue and cell cultures, the quantitation of random and special lymphocyte and macrophage interactions with cancer and other cells, and observations of the responses of the preparations to various challenges can contribute to the understanding of the neoplastic process in the individual patient with cancer.
A single three-dimensional chromatin compartment in amphioxus indicates a stepwise evolution of vertebrate Hox bimodal regulation
Authors: Rafael D Acemel, Juan J Tena, Ibai Irastorza-Azcarate, Ferdinand Marlétaz, Carlos Gómez-Marín, Elisa de la Calle-Mustienes, Stéphanie Bertrand, Sergio G Diaz, Daniel Aldea, Jean-Marc Aury, Sophie Mangenot, Peter W H Holland, Damien P Devos, Ignacio Maeso, Hector Escrivá, José Luis Gómez-Skarmeta
Journal: Nature Genetics (2016)
Inhibitory Effects of Tetragastrin and Histamine on Carcinogenesis in the Small Intestines of W Rats by &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N&lt;/italic&gt;'-nitro-&lt;italic&gt;N&lt;/italic&gt;-nitrosoguanidine&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M Tatsuta, H Iishi, M Ichii, S Noguchi, H Yamamura, H Taniguchi
Journal: JNCI Journal of the National Cancer Institute (1986)

The effects of tetragastrin and histamine on the incidence and histology of tumors induced in the small intestine by N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7] were investigated in male W rats. Animals were given MNNG at 150 micrograms/ml in their drinking water for 25 weeks and then 300 micrograms tetragastrin or 4 mg histamine dihydrochloride sc per day in depot form. Administration of tetragastrin or histamine after MNNG treatment resulted in a significant increase in gastric acid secretion and a significant reduction in the incidence of tumors in the duodenum; however, only histamine decreased the incidence of tumors in the jejunum. Histologically, the tumors induced in the small intestine were mostly adenocarcinomas, and their histologic type was not affected by either tetragastrin or histamine.
The concept of an overview of cancer clinical trials with special emphasis on early breast cancer.
Authors: R D Gelber, A Goldhirsch
Journal: Journal of Clinical Oncology (1986)

Overviews are valuable investigations that require international cooperation, and can provide a useful summary of available information on a current therapeutic issue. Combining results of trials in early breast cancer is an appropriate example of such procedures. However, the advantage of bringing a large amount of information together might be overcome by the disadvantages of improper conduct and overinterpretation of the overview findings. A prospective protocol must be prepared and followed. The results must be presented in sufficient detail to allow independent conclusions to be reached. The influence of strict application of the arithmetic construct must be recognized when determining whether the conclusions about the impact of separate components of treatment are appropriate. Most importantly, the transition from scientific inquiry to the application of treatment recommendations for individual patients must still be made very cautiously. We stress the importance of the results from individual, well-conducted clinical trials for providing the critical information for guiding the choice of treatment for patients outside of trials.