tbuckley/cabot-search huggingface dataset:
A randomized pilot study of acupuncture for control of treatment-induced menopausal symptoms in breast cancer patients
Authors: L. Rockwell, G. Makari-Judson, J. Moran, J. Varner, R. Barham, W. C. Mertens
Journal: Journal of Clinical Oncology (2008)

20543 Background: Breast cancer patients often experience menopausal symptoms not relieved by current therapies. Preliminary data suggest possible relief of vasomotor symptoms and improved quality of life (QoL) in patients receiving acupuncture. Methods: Acupuncture and sham acupuncture were compared in women with breast cancer and hot flashes for at least one month severe enough to warrant treatment. Anti-depressants were permitted if taken for at least 6 months without improvement. Consenting subjects were randomly assigned to a 4 week observation period followed by either 7 weeks of acupuncture then 7 weeks of sham acupuncture using non-piercing Streitberger needles (group A) or the same therapy with the sequence reversed (group B). Ten acupuncture and ten sham treatments were delivered by the same practitioners to each group. Women maintained daily hot flash diaries and weekly Menopause-Specific QoL (MSQoL) questionnaires during treatment. Results: Twenty-one patients consented; 4 withdrew within the first week; 17 patients were evaluated (group A: 7; group B: 10). Hot flash number decreased with the first therapy sequence (7.0/day vs. 9.1/day in the observation period p=0.0003), as did severity (p<0.0001) but no differences between the arms were seen. Overall MSQoL improvements were seen in group A after acupuncture compared with sham in group B at week 11 (p=0.05); MSQoL menopausal symptom complex also significantly improved (mean decrease 9.8 vs. 4.0, p=0.0009). No differences between groups were seen at the end of the study. Conclusions: While daily diaries did not exhibit a difference between acupuncture or sham intervention for either hot flash number or severity in this small study, a significant improvement in menopausal symptoms and overall QoL in the acupuncture-treated women was demonstrated on weekly MSQoL. A larger phase III study comparing acupuncture with pharmacologic treatments should be considered. No significant financial relationships to disclose.
A KRAS-variant as a biomarker of ovarian cancer risk.
Authors: J. B. Weidhaas
Journal: Journal of Clinical Oncology (2010)

5016 Background: Ovarian cancer is the single most deadly form of women's cancer, largely due to a lack of known risk factors or genetic markers. The KRAS oncogene and altered levels of the microRNA let-7 are associated with an increased risk of developing solid tumors. We investigated the association of a single nucleotide variant (rs61764370), referred to as the KRAS-variant, previously shown to disrupt a let-7 microRNA binding site in the KRAS oncogene 1, and ovarian cancer risk. Methods: Specimens were obtained and tested for the presence of the KRAS-variant from nonselected ovarian cancer patients in three independent cohorts (n = 457), from two independent ovarian case-control studies (n = 866), and from ovarian cancer patients with hereditary breast and ovarian cancer (HBOC) syndrome (n = 58) as well as in their family members. Results: Our results indicate that the KRAS-variant is associated with greater than 25% of non-selected ovarian cancer cases, and is a marker for a significant increased risk of developing ovarian cancer as confirmed by two independent case control analyses. The KRAS-variant was also identified in 60% of HBOC patients without BRCA1 or BRCA2 mutations, previously considered uninformative, as well as in their family members with cancer. Furthermore, the KRAS-variant predicted significantly worse outcome from ovarian cancer for its carriers. Conclusions: These findings strongly support the hypothesis that the KRAS-variant is a genetic marker of an increased risk of developing ovarian cancer, and suggests that the KRAS- variant may be a new biomarker of risk for HBOC families without other known genetic abnormalities. In addition, the KRAS-variant predicts for the most deadly ovarian cancers, which are likely the most important to prevent or catch early. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MiraDx
Potent chemopreventive/antioxidant activity detected in common spices of the Apiaceae family in vitro
Authors: Jeyaprakash Jeyabalan, Lisa Soper, Harini Aiyer, Ramesh Gupta
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4986 

Epidemiological data suggest an association of elevated levels of estrogens with breast cancer development. In particular, the natural female hormone, 17β-estradiol (E2), and its major metabolite, 4-hydroxy-17β-estradiol (4E2), produced selectively at the target site, have been implicated in the cancer development, and it is believed that these substances cause free radical-mediated, direct and/or indirect DNA damage. In attempts to discover new agents of natural origin, we have examined common spices of the Apiaceae family for bioactivity in reducing this damage. Besides their use in numerous cuisines, the Apiaceae spices have long been used in folklore medicine, as digestive, anti-inflammatory, and antidiabetic agents. In this study, we report efficacy of aqueous and non-aqueous extracts of six Apiaceae spices (anise, caraway, coriander, cumin, dill and fennel) for free radical-scavenging activity and activity to inhibit cytochrome P450 in two separate reactions, involving: i) E2, rat liver microsomes, co-factors, DNA and CuCl2; and ii) 4E2, DNA and CuCl2. The spices, extracted thrice in water and in acetonitrile were pooled and reconstituted respectively. Oxidative DNA adducts resulting from redox cycling of 4E2 were analyzed by 32P-postlabeling. Compared with vehicle treatment, both the aqueous (72% - 96%) and non-aqueous (82% - 94%) extracts substantially inhibited adduct formation in the microsomal reaction. However, in the non-microsomal reaction, only the aqueous extracts showed the inhibitory activity (82% - 96%). At 5-times lower concentrations, aqueous extracts of cumin and dill still elicited significant adduct inhibition (60% - 73%). By comparison, the well-known antioxidants, β-carotene and ellagic acid (300 µM) showed about 30% and 90% adduct inhibition, respectively in the non-microsomal reaction. These results suggests the presence of two groups of chemicals in the spices - polar compounds (water soluble) that have free radical-scavenging activity, and lipophilic compounds (soluble in acetonitrile) that selectively inhibit P450 activity associated with estrogen metabolism. Because of their wide-spread use with no known toxicity, potent antioxidant activity, ability to inhibit P450s and other previously known actions (e.g., anti-inflammatory), the Apiaceae spice phytochemicals may be potentially useful to inhibit estrogen-mediated breast cancer and other hormonal cancers (Supported in part from Agnes Brown Duggan funds).
Erythropoietin receptor expression in bladder cancer
Authors: C. Belda Iniesta, J. De Castro Carpeño, E. Casado Saenz, J. Feliu Batlle, F. Bernabeu, J. Alves, P. Cejas, M. Sereno, R. Perona, M. Gonzalez Baron
Journal: Journal of Clinical Oncology (2006)

4584 Background: Several groups have implicated erythropoietin receptor (EPOR) expression in cancer progression, angiogenesis and cell survival. No clinical data about its implication in bladder cancer has been reported. So, our main objective was to determine the expression of EPOR in bladder cancer specimens after radical cystectomy and its potential relation with disease free survival (DFS) and overall survival (OS). Methods: Patients diagnosed with invasive grade 3 bladder cancer were included after radical cystectomy. None of them had node involvement after pathological examination. Data about pathological stage (pT), DFS and OS were recorded. EPOR expression was analyzed by immunohistochemistry in paraffin embedded samples. An expert uro-pathologist ensured enough tumoral proportion in every sample. EPOR antibody was targeted against the extracellular domain of this receptor (Santa Cruz, CA). Positive immunostaining was defined when more than 80% tumoral cells showed a cytoplasmatic staining pattern. Results: Of the 75 consecutive patients included (pT1 = 11; pT2 = 21; pT3 = 21; pT4 = 22), 40 (53.3%; 95% CI 42.61- 64.23) had EPOR expression. No correlation was observed between EPOR expression and pathological stage. Median DFS was 10 months for patients with EPOR expression and was not reached for individuals without receptor expression after 22 months of follow-up (logrank test p &lt; 0.0001). Furthermore, univariate analysis showed that pathological stage had no statistical influence. Finally, multivariate analysis showed only EPOR expression as predictor for DFS and OS (p = 0.0009). Conclusions: EPOR expression is a strong prognostic factor after radical cystectomy in grade 3 bladder cancer patients without node involvement. No significant financial relationships to disclose.
Homoharringtonine-induced hyperglycemia.
Authors: R K Sylvester, M Lobell, W Ogden, J A Stewart
Journal: Journal of Clinical Oncology (1989)

Homoharringtonine (HHT) has been reported to induce hyperglycemia. This report describes a study conducted to characterize the effect of HHT on insulin production and action. Our data indicate that HHT-induced hyperglycemia results from the development of insulin resistance. A review of the literature suggests that patients receiving HHT continuous infusions of 5 mg/m2/d or greater and patients greater than 10 years of age may be at increased risk for the development of HHT-induced hyperglycemia. We recommend that patients with these risk factors, as well as diabetic patients and patients concurrently receiving asparaginase and/or prednisone, have their blood glucoses routinely monitored for hyperglycemia.
Pharmacokinetics (PK) of RSR13 (efaproxiral) predict survival in patients with brain metastases randomized to receive whole brain radiation therapy (WBRT) with or without RSR13 (REACH RT-009)
Authors: E. Shaw, B. Stea, T. Pinter, Y. Hammoud, P. J. Cagnoni, J. Hackman, A. Boyd, M. Craig, J. Marks, J. Suh
Journal: Journal of Clinical Oncology (2004)

1561 Background: 538 patients with brain metastases from selected solid tumors were randomized in a study of standard WBRT (30 Gy in 10 fractions) and supplemental oxygen with or without the radiation sensitizer RSR13 (efaproxiral) (Control n=267, RSR13 n=271). A non-significant improvement in MST was seen in favor of the RSR13 arm when results were analyzed by undajusted log-rank. The study showed a survival advantage for RSR13-treated patients versus controls after adjusting for imbalances in prognostic factors (Cox multiple regression) with the patients with breast cancer deriving the largest benefit from RSR13. Since a clear PK/Pharmacodynamic (PK = RSR13 concentration in RBCs and Pharmacodynamic = p50 shift) correlation had been established for RSR13 in previous studies, PK analyses were incorporated in the design of the present study. Methods: Blood samples were drawn for RSR13 PK analyses on Day 1 of RSR13 and at least once during the second week of RSR13 therapy. 188 patients had at least 2 PK determinations, 64 had 1 PK determination and 19 had no PK evaluation. Results: Higher PK were observed in patients with higher body weight and in women. Patients were assigned to 1 of 5 groups based on the number of WBRT fractions and the number of RSR13 doses received, as shown in the table below. Conclusions: These analyses reveal that patients with RSR13 concentrations in RBCs that reached optimal levels had a better outcome than those patients who did not. A clear correlation between PK, number of RSR13 doses, and MST was established. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Allos Therapeutics, Inc. Allos Therapeutics, Inc. Allos Therapeutics, Inc.
Case-control study of height, weight and BMI and breast cancer risk in Nigerian women
Authors: T. O. Ogundiran, D. Huo, C. A. Adebamowo, A. A. Adenipekun, O. B. Campbell, O. I. Olopade
Journal: Journal of Clinical Oncology (2008)

1506 Background: Studies in affluent Western countries have shown that weight was protective against breast cancer in premenopausal women but was a risk factor in postmenopausal women. However, different relationship between weight and breast cancer was observed in non-Western countries. Height was positively correlated with breast cancer risk but it has been hypothesized that the association is stronger in populations where childhood growth was limited by energy deprivation. To clarify these issues, we examined the association between height, weight and breast cancer risk in a large case-control study in Nigeria. Methods: Consecutive cases of female breast cancer patients aged 18 years and above, attending the surgical oncology and radiotherapy clinics of the University College Hospital, Ibadan, Nigeria between 1998 and 2006 were recruited in the study. Eligible controls who were free of cancer were recruited from a community in Ibadan. Trained nurses administrated structured questionnaires to collect epidemiologic data. Logistic regression models were used to examine the relationship between anthropometric measures and breast cancer. Odds ratio (OR) (adjusted for multiple confounders) and 95% confidence interval (CI) were calculated. Results: There were 820 cases and 569 controls. Cases (46.9 ± 11.3 years) were older than controls (41.2±13.8 years). Cases (160.2 ± 6.8 cm) were on average 1.7 cm taller than controls (158.5 ± 6.6 cm). The adjusted OR comparing the highest (≥ 165 cm) to the lowest quartile (< 155 cm) of height was 2.22 (95% CI 1.48–3.31, p trend < 0.001), with an OR of 1.22 (95% CI 1.10–1.35) for each 5-cm increase. Body mass index had an inverse relationship with breast cancer risk in all women, with an OR of 0.79 (95% CI 0.70–0.89, p trend = 0.009) for each 5 kg/m2 increase, regardless of menopausal status. Similar result was obtained for absolute weight. Conclusions: The influence of height was stronger in indigenous Africans than in previous studies, suggesting energy intake in earlier life may be important in breast cancer development. In contrast to previous findings, we found a protective effect of BMI on breast cancer in both premenopausal and postmenopausal women, which underscores the need for studies of larger cohorts of indigenous African women. No significant financial relationships to disclose.
The combination of rituximab and GM-CSF in elderly patients with chronic lymphocytic leukemia (CLL)
Authors: A. Ferrajoli, S. O’Brien, S. Faderl, W. G. Wierda, E. Schlette, J. L. Jorgensen, J. M. Reuben, M. Albitar, M. J. Keating
Journal: Journal of Clinical Oncology (2006)

6602 Background: CLL is a disease found more frequently in the elderly (50% of the patients are age ≥70 at diagnosis). Nevertheless treatment startegies for elderly patients have not been optimized. Elderly patients are often excluded from chemotherapy programs because of fear of severe toxicities resulting from myelosuppression. Therefore, we explored the activity of rituximab in combination with GM-CSF in elderly patients with CLL. The rationale for this combination stems from in vitro data showing increased activity of rituximab when administered togheter with GM-CSF (Venugopal P. Leuk. Res.2000). Methods: Patients age ≥70 years, untreated or previously treated, were eligible if they had indications for treatment (NCI-WG criteria). Treatment consisted of rituximab 375 mg/m 2 administered weekly for 4 weeks and GM-CSF 250 mcg s.q. three times weekly for 8 weeks. In the first week GM-CSF was given on day 1 and 3 and rituximab was given on day 4. Genomic aberrations, IgV H mutation status, ZAP-70 and CD38 expression were evaluated prospectively. Correlative studies measured changes in cell surface and soluble CD20, apoptosis and quality of life (FACT-An V4). Results: 39 patients have been enrolled, 28 are evaluable for response and 31 for toxicity. According to NCI criteria the OR rate was 61%. 7% of the patients achieved CR, 11% nodular PR and 43% PR. Thirty patients are alive and the median time to treatment failure has not been reached with a median follow up of 5 months. Toxicity attributable to GM-CSF was G1 injection site reaction observed in 16% of the patients. OR rates were higher in naive than in previously treated patients (74% vs 46%), in patients with favorable genomic features (73% vs 40%) and mutated IgV H (89%vs 44%). No difference in OR was found in patients expressing high or low CD38 (60% vs 55%). Upregulation of surface CD20, measured 24h after the 2nd dose of GM-CSF, was observed in 3 out of 4 patients studied. Fatigue level was reduced by a mean of 7 points according to the FACT-An scale (6 patients). Conclusions: Treatment with rituximab and GM-CSF induced a high response rate with minimal toxicity in elderly patients with CLL. Priming with GM-CSF resulted in increased expression of surface CD20. This combination of rituximab and GM-CSF improved systemic symptoms such as fatigue. [Table: see text]
The HIV protease inhibitor nelfinavir is synergistic with energy restriction in SQ20b cells resulting in down-regulation of phosphorylated Akt and radiation sensitization
Authors: A. K. Gupta, W. W. Wilke, J. M. Buatti, D. R. Spitz
Journal: Journal of Clinical Oncology (2008)

22212 Background: We have recently shown that some HIV protease inhibitors (HPIs) can result in down-regulation of the PI3K-Akt pathway. This can be clinically useful in the treatment of human malignancies as activation of this pathway is frequently seen and is associated with resistance to radiation. Emerging evidence in human population studies has begun to indicate that dietary energy restriction is protective in preventing cancer. In animal models, energy restriction has also been shown to be therapeutic in treating cancer. We decided to investigate the effect of energy restriction by using 2-deoxyglucose (2-DG), an inhibitor of glucose metabolism that has been suggested to be capable of radiosensitizing tumor cells via energy deprivation as well as enhancing oxidative stress, in combination with the HPI nelfinavir (NFV) in the head and neck squamous cancer cell line SQ20b which has constitutive activation of EGFR resulting in activation of the PI3K-Akt pathway rendering it resistant to radiation. Our goal was to compare NFV, 2-DG and the combination. Methods: SQ20b head and neck squamous cancer cells with an activating mutation in EGFR were used. Nelfinavir was bought from our in-patient pharmacy. 2-DG was purchased through Sigma. Western blots were done to evaluate signaling from the PI3K-Akt pathway. Clonogenic assays were done with and without drug treatment. Results: We found that treatment of SQ20b cells for 3 days with 10 μM NFV or 1 day of 20 mM 2-DG resulted in down-regulation of Akt activity and radiation sensitization. The effect was more pronounced with NFV than with 2-DG. The combination of both NFV and 2-DG was synergistic both in terms of down-regulation of Akt signaling and radiation survival. Conclusions: We have previously shown that the HIV protease inhibitor nelfinavir (NFV) de-phosphorylates Akt at clinically relevant doses and sensitizes SQ20B cells to radiation. Here we show that this effect can be further enhanced by energy deprivation using 2-deoxyglucose. Studies are currently in progress evaluating NFV in combination with radiation. 2-DG is currently undergoing phase 1 studies in human cancer. Future trials should evaluate the combination of 2-DG and NFV. No significant financial relationships to disclose.
Abstract 13929: Clinical Usefulness of HAS-BLED Score to Predict Cardiovascular Outcome in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention with Stenting
Authors: Yusuke Iwasaki, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Kawasaki Masato, Kikuchi Atsushi, Takashi Naito, Tadao Fujimoto, Kentarou Ozu, Takumi Kondo, Kaoruko Sengoku, Hironori Yamamoto, Tsutomu Kawai, Satoshi Takahashi, Masatake Fukunami
Journal: Circulation (2012)

Backgruond: Oral anticoagulant therapy (OAC) with dual antiplatelet therapy increases the risk of hemorrhagic complications in patients with AF undergoing percutaneous coronary intervention (PCI) w...
Chromosomal Studies in Bovine Lymphosarcoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W. C. D. Hare, R. A. McFeely, D. A. Abt, J. R. Feierman
Journal: JNCI Journal of the National Cancer Institute (1964)

Nine cases of bovine lymphosarcoma were studied and, in all but one, varying proportions of cells with changes in their chromosomal constitution were found. The studies were made on cells obtained from short-term, peripheral blood leukocyte cultures and/or directly from lymph nodes. Changes involved alterations in the chromosomal numbers to give either hypodiploid or hyperdiploid constitutions. No constant pattern of aneuploidy or structural change was found, but in 4 cases the abnormal karyotypes were without one of the submetacentric or sex chromosomes. Two others had cells with the same marker chromosomes in more than one lymph node. In 4 cases, cells from lymph nodes had abnormal karyotypes, whereas those from peripheral blood cultures had apparently normal karyotypes.
Abstract 18701: Frequency and Contributing Factors to Diaphragm Paresis Following Pediatric Cardiac Surgery
Authors: Intikhab Zafurallah, Osami Honjo, Peter Laussen, Cathy MacDonald, Alejandro Floh
Journal: Circulation (2014)

Introduction: Diaphragm paresis can occur as a complication of pediatric cardiac surgery that can prolong ventilation and length of ICU stay. Diaphragm plication (DP) may be necessary to improve respiratory mechanics and decrease duration of ventilation support. Early identification of patients who are likely to benefit from DP has not been studied. Methods: Patients at our institution diagnosed with diaphragm paresis between 2002 - 2012 were identified. Mode of diagnosis, demographics, operative procedures during index admission, and intervals of care were evaluated. Associations between predictors and DP were assessed by univariable and multivariable logistic regressions. Results: Diaphragm paresis was diagnosed in 161 patients following 6448 index surgeries, of whom 31 (19%) underwent DP (DP+). Paresis was diagnosed by ultrasound in 160 (99%) subjects at a median (IQR) time from surgery of 7 (3, 11) days in DP+ vs 10 (6, 19) days in DP- (p=0.02). DP was completed after a median (IQR) of 4 (1, 17) days after diagnosis. DP+ were younger in age [median (IQR) days DP+ 42 (14, 84) vs DP- 168 (28, 784); p&lt;0.001], underwent surgery of higher RACHS-1 score [DP+ 3 (3, 4) vs DP- 3 (2, 4); p=0.02], and had a higher rate of hypothermic circulatory arrest [DP+ 14 (45%) vs DP- 23 (18%); p=0.001]. DP+ subjects had a rate of single ventricle physiology (32%), median sternotomy (94%), and bypass (87%) similar to DP- subjects. Only younger age (OR 1.003 per day, p=0.02) and use of hypothermic circulatory arrest (OR 3.06, p=0.01) remained significant on multivariable modeling. DP+ subjects had longer duration of ventilator support [DP+ 15 (9, 30) vs DP- 6.5 (3, 12.5) days; p&lt;0.001] and ICU admission [DP+ 23 (18, 42) vs DP- 8 (5, 17) days; p&lt;0.001]. However, ventilation was discontinued after a median of 1 (1,2) day after plication. The time interval from index surgery to diagnosis (EST 0.91, p&lt;0.0001) and interval from diagnosis to DP (EST 0.94, p&lt;0.0001; r2=0.91) were associated with a longer ICU stay even after adjusting for age and bypass time. Conclusion: Diaphragm paresis is common after congenital heart surgery. Earlier diagnosis and plication may shorten length of ventilation support and ICU stay, particularly in younger patients. Long-term outcome studies following DP are required.