tbuckley/cabot-search huggingface dataset:
P09.23 Tumor Treating Fields delivery using second generation Optune® system for glioblastoma treatment: patient experience and compliance
Authors: A. Kinzel, M. Ambrogi, M. Varshaver, L. Benson, E. Kirson
Journal: Neuro-Oncology (2017)

Significance and Background: Tumor Treating Fields (TTFields) are non-invasive, low-intensity electric fields with anti-mitotic activity delivered using the Optune® System, which is approved for the treatment of adult patients with newly diagnosed and recurrent supratentorial glioblastoma (GBM). TTFields are delivered via 4 transducer arrays that are applied directly to the scalp to target the tumor. The first generation Optune® system consisting of a field generator, portable lithium batteries, carrying bag, and transducer arrays weighed approximately ~ 2.7 Kg (6 pounds). The system has been redesigned to improve the convenience and manageability of TTFields therapy for GBM patients. The second generation Optune® System uses new digital signal generation technology to reduce the size and weight to ~ 1.2 Kg (2.7 pounds) including the battery, which may positively affect patient convenience and compliance with treatment. Purpose: To understand the effect of size and weight advantages of the second generation Optune® System on patient satisfaction, compliance (time on therapy), and usability. Interventions: Ten GBM patients (N=10, male = 8, female = 2, median age: 52.9 years [31-79]) were monitored at multiple time points over the first month of transitioning to the second generation Optune® System using a questionnaire assessing the convenience and ease of daily usage as well as duration of daily use and frequency of complications associated with usage (alarms). Evaluation: A 10 point numerical analog scale was utilized to assess feedback at baseline (on the original system) and at 5 specific time points over the first month of second generation Optune System usage. Patient feedback highlighted the benefits of enhanced features such as quieter operation and portability. Discussion: Overall, patients were very satisfied with the new system in terms of convenience and usability and experienced less number of alarms. Patient compliance using the second generation Optune® System was maintained and in most cases improved compared with the original Optune® System. Innovation: TTFields treatment that target compliance rates of 75% (18 hours per day) improve survival outcomes as observed in GBM clinical trials. The results of this patient survey indicate that the improved size, weight and convenience of the second generation Optune® System help patients comply with daily treatment duration goals.
P01.24 Rapid adaptation to metabolic stress depend on microRNA expression in Glioma
Authors: D. Ogawa, K. I. Ansari, M. Okada, K. Miyake, T. Tamiya, E. Chiocca, A. Bronisz, J. Godlewski
Journal: Neuro-Oncology (2017)

Glioblastoma is known as its rapid proliferation and invasion. Because of its aggressiveness, growth of Glioblastoma often exceed speed of angiogenesis and encounters metabolic stress including glucose availability. In order to survive under this nutrient starvation, Glioblastoma switch metabolism from energy consumption to ATP conservation by activating AMPK. We report how far the expression level of microRNA affect Glioblastoma to rapidly adapt glucose depletion induced metabolic stress. MicroRNA-451 indirectly inactivate AMPK by targeting CAB39, a component of LKB1. Among various expression levels of microRNA-451 in primary GBM cell lines, higher expression level of microRNA-451 showed delay in adaptation to poor nutritious environment. This mechanism may be useful to therapeutic enhancement by stressing Glioblastoma metabolism.
Biomarkers that predict sensitivity to heat shock protein 90 inhibitors (HSP90i).
Authors: Komal L. Jhaveri, Neil M. Iyengar, Adriana Corben, Sujata Patil, Muzaffar Akram, Russell Towers, Rita Sakr, Clifford Hudis, Tari A. King, Neal Rosen, Sarat Chandarlapaty, Shanu Modi
Journal: Journal of Clinical Oncology (2012)

10618 Background: HSP90 is an attractive target in tumors as it mediates the maturation and stabilization of client oncoproteins. HSP90i are potentially active in a variety of tumors, but therapeutic benefit is confirmed in only a small subset to date. Predictive biomarkers could identify patients (pts) and/or tumors with sensitivity to HSP90i improving the therapeutic index. We explored potential biomarkers across multiple studies of HSP90i. Methods: Archived pre-treatment tumor specimens from pts treated with any of several HSP90i (17-AAG, 17-DMAG, CNF2024, retaspimycin &amp; ganetespib) on 8 phase I/II trials at MSKCC from 1999 to 2011 were identified. The following antibodies were validated at MSKCC and tumor tissue was tested by immunohistochemistry (IHC) with results defined for each as: ER, PR &amp; AR: &gt;1% pos &amp; &lt;1% neg; HSP90 &amp; HSP70: 0, 1+ neg &amp; 2+, 3+ pos; PTEN: 0, 1+ neg &amp; 2+ pos; HER2: 0, 1+ neg, 2+ equivocal, 3+ pos; EGFR: 0 neg &amp; 1+, 2+, 3+ pos. Clinical response was correlated with IHC using Fisher’s exact test. Results: Of the 164 pts identified, adequate tissue was available for 51, including 11 different solid tumors &amp; 1 CML. Breast (N=31), melanoma &amp; prostate (N=4 each) were most frequent. The mean age at primary diagnosis was 50 yrs (24-81). The median no. of lines of prior chemotherapy for metastatic disease was 2 (0-8). The mean duration of HSP90i therapy was 79 days (0-411). There were 19 responses (5 PR; 14 SD); 14/19 responses strongly correlated with HER2+ status (p = 0.001); 1 pt with ER+/HER2-/EGFR- &amp; 4 with EGFR +/HER2-/ER- disease also responded. A correlation for ER &amp; EGFR with response was not excluded (p=0.07 &amp; p=0.086 respectively). Conclusions: Our findings confirm HER2 as a sensitive client and an effective biomarker for sensitivity to HSP90 inhibitors. ER &amp; EGFR did not meet statistical significance but may warrant further exploration in prospective settings.
P09.11 Wavelength-specific lighted suction instrument for 5-aminolevulinic acid fluorescence-guided resection of deep-seated malignant glioma
Authors: S. J. Han, R. A. Morshed
Journal: Neuro-Oncology (2017)

Introduction: 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery has become a valuable adjunct in the resection of malignant intracranial gliomas. Furthermore, the fluorescence intensity of biopsied areas of a resection cavity correlates with histological identification of tumor cells. However, in the case of lesions deep within a resection cavity, light penetration may be suboptimal, resulting in less excitation of 5-ALA metabolites leading to decreased fluorescence emission. Here, we demonstrate the use of a 400 nm fiber optic light source incorporated into a surgical suction instrument that simultaneously allows for removal of blood products and improvement of tumor fluorescence by providing necessary wavelength-specific illumination to deeper areas of a resection cavity. Materials and Methods: A SpetzlerTM Lighted Suction Tube (Kogent Surgical, Chesterfield, MO) was connected to a custom-designed 400 nm wavelength emitting light source built using a Luxtec model LX-300 fiber optic illuminator (Integra, Plainsboro, NJ) with a 400 nm filter (Product number #84-781, Edmund Optics, Barrington, NJ) installed in the optical path. The 400 nm lighted suction instrument was used during the resection of the tumor, both for removing blood products and tumor tissue as well as to illuminate areas of the deep resection cavity to probe for remaining areas of 5-ALA positivity. Results: We present the techniques described, including the intraoperative set-up and the equipment utilized. We also describe the use of this technique in several cases of malignant glioma resection. This technique improved the fluorescence intensity of patches of malignant tissue deep within the resection cavity. Light emanating from the instrument did not cause auto-fluorescence when no 5-ALA positive tissue was present. Furthermore, no evidence of photo-bleaching or tissue damage was seen intraoperatively in areas in which the fluorescent light was used. Conclusions: This technique may further improve 5-ALA’s utility in identifying tumor infiltrated tissue for deep-seated lesions. Additionally, this tool may have implications for standardizing the intensity of the blue light exposure on tissues when assessing or quantifying the 5-ALA fluorescence intensity.
Abstract 162: Single Nucleotide Polymorphism of the B-Type Natriuretic Peptide Helps Predict the Presence of Significant Coronary Artery Disease
Authors: Terry Y Li, M. Y Tse, Nicole M Ventura, Marie-France Hetu, Amer M Johri, Stephen C Pang
Journal: Circulation Research (2014)

Early detection and diagnosis of coronary artery disease (CAD) is crucial in reducing the morbidity and mortality. The clinical standard for detecting CAD is by angiography which is associated with rare but important clinical risks. Recent studies have shown that up to 40% of patients referred for angiography do not have significant disease. This discrepancy between referral and diagnosis may be improved by the utilization of genetic screening. A single nucleotide polymorphisms (SNP) of the B-type natriuretic peptide gene (NPPB), rs198389, was previously found to be associated with several cardiovascular diseases. Our objective was to determine whether detection of genetic variation could contribute to better selection of patients referred for angiography. We hypothesized that an SNP analysis of the NPPB gene may help differentiate patients with significant disease from those with non-significant CAD. Ninety-three patients referred for coronary angiography at the Kingston General Hospital Cardiac Catheterization Lab were consented for genetic screening. Blood samples were collected during angiography procedure. Genomic DNA was isolated from leukocytes, and screened for SNPs using a real-time PCR-based TaqMan SNP Assay. We found that more males were referred for coronary angiography than females: 69% versus 31%. Two out of ten males (20%) were found to have no or minimal CAD. In contrast, 48% of females were found to have non-significant CAD. Older age (≥ 69 years) was deemed to be a significant predictor of CAD in the total recruited population (odds ratio of 3.4), but no age difference was found between healthy and diseased females. Additionally, a mutation of the B-type natriuretic peptide gene (NPPB) was found to be a significant predictor of CAD in the younger population (&lt; 69 years), with an odds ratio of 5.9. We found a significant difference between patterns of CAD development in males and females, suggesting that different diagnostic criteria should be used depending upon gender. Moreover, younger individuals with two copies of the major allele for the NPPB SNP were more likely to develop CAD, making this SNP a potential factor in the prediction of CAD in younger population.
Bronchoalveolar lavage findings for the diagnosis of radiation pneumonitis in rats.
Authors: Young-Taek Oh, Kwang-Ju Park, Hoon-Jong Kil, Jung-Hye Hwang, Seung-Hee Kang, Mison Chun
Journal: Cancer Research (2004)

3114  Purpose: Radiation pneumonitis is a common complication after radiation therapy for lung cancer. The diagnosis is based on clinical features; however, it is often difficult. Bronchoalveolar lavage (BAL) is a powerful tool for studying and diagnosing various pulmonary disorders. We assessed BAL findings in the diagnosis of radiation pneumonitis in rats. Materials and Methods: Sprague-Dawley rats received 5 or 20 Gy of radiation to the right lung. BAL was performed for the right and left lungs separately 3, 7, 14, 28, and 56 days after radiation. The cells in the BAL fluid were counted and the expression of iNOS and TGF-b by alveolar cells was evaluated using RT-PCR. The concentrations of protein, NO, and TGF-b in the BAL fluid were measured. Results: On histology, 20 Gy of radiation resulted in lung damage from 2 weeks on, while 5 Gy of radiation produced no significant changes. Protein leakage was observed at 4 weeks and TGF-b in the BAL fluid was increased at 8 weeks for the right lung receiving 20 Gy of radiation. Lymphocytes and neutrophils were recruited at 2 and 8 weeks, respectively, and NO was increased at 4 weeks for both irradiated and non-irradiated lungs. These findings were also seen in the rats that received 5 Gy of radiation, although the changes were not significant compared with the lungs that received 20 Gy of radiation. There were no significant changes in TGF-b or iNOS expression. Conclusion: This study documented the typical BAL findings of the lung with radiation pneumonitis. Cellular feature and increased protein, TGF-b and NO level in BAL fluid were significant BAL findings suggestive of radiation pneumonitis in rats after 20 Gy of radiation. BAL could be helpful for the clinical diagnosis of radiation pneumonitis.
Impact of New Anti-Leukemia Agents on Transplant Outcomes in Adults with Acute Lymphoblastic Leukemia (ALL) Undergoing Allogeneic Hematopoietic Cell Transplantation (HCT) in Second Complete Remission
Authors: Sara Lozano Cerrada, David Marin, Gabriela Rondon, Celina Ledesma, Uday R. Popat, Amanda L. Olson, Amin M. Alousi, Betul Oran, Sairah Ahmed, Stefan O. Ciurea, Krina Patel, Elizabeth J. Shpall, Chitra Hosing, Muzaffar H. Qazilbash, Nina Shah, Katayoun Rezvani, Elias Jabbour, Hagop M. Kantarjian, Richard E. Champlin, Partow Kebriaei
Journal: Blood (2016)
Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients With Cancer
Authors: Nobuyuki Katakami, Koji Oda, Katsunori Tauchi, Ken Nakata, Katsunori Shinozaki, Takaaki Yokota, Yura Suzuki, Masaru Narabayashi, Narikazu Boku
Journal: Journal of Clinical Oncology (2017)

Purpose This randomized, double-blind, multicenter study aimed to determine the dose of naldemedine, a peripherally-acting μ-opioid receptor antagonist, for future trials by comparing the efficacy and safety of three doses of naldemedine versus placebo in patients with cancer and opioid-induced constipation. Methods Patients ≥ 18 years old with cancer, an Eastern Cooperative Oncology Group performance status ≤ 2, who had been receiving a stable regimen of opioid analgesics for ≥ 2 weeks, had at least one constipation symptom despite laxative use, and no more than five spontaneous bowel movements (SBMs) during the past 14 days, were randomly assigned (1:1:1:1) to oral, once-daily naldemedine 0.1, 0.2, or 0.4 mg, or placebo, for 14 days. The primary end point was change in SBM frequency per week from baseline during the treatment period. Secondary end points included SBM responder rates, change from baseline in the frequency of SBM without straining, and complete SBM. Safety was also assessed. Results Of 227 patients who were randomly assigned, 225 were assessed for efficacy (naldemedine 0.1 mg, n = 55; 0.2 mg, n = 58; 0.4 mg, n = 56; placebo, n = 56) and 226 for safety. Change in SBM frequency (primary end point) was higher with all naldemedine doses versus placebo ( P < .05 for all comparisons), as were SBM responder rates and change in complete SBM frequency. Change in SBM frequency without straining was significantly improved with naldemedine 0.2 and 0.4 (but not 0.1) mg versus placebo (at least P < .05). Treatment-emergent adverse events were more common with naldemedine (0.1 mg: 66.1%; 0.2 mg: 67.2%; 0.4 mg: 78.6%) than placebo (51.8%); the most common treatment-emergent adverse event was diarrhea. Conclusion Fourteen-day treatment with naldemedine significantly improved opioid-induced constipation in patients with cancer and was generally well tolerated. Naldemedine 0.2 mg was selected for phase III studies.
Use and Patterns of Supportive Care Among Patients Receiving Myelosuppressive Chemotherapy for Breast Cancer, Colorectal Cancer, Lung Cancer, or Non-Hodgkin's Lymphoma in US Clinical Practice
Authors: Derek Weycker, Amanda Silvia, Kathryn Richert-Boe, Mark Bensink, James O. Brady, Lois Lamerato, Heather Lipkovich, Ahmad Daniyal Siddiqui, David Chandler
Journal: Blood (2016)
NO EFFECT OF TENOFOVIR OR ENTECAVIR ON VITAMIN D LEVELS IN CHRONIC HEPATITIS B MONO-INFECTED PATIENTS. SINGLE CENTRE 'REAL LIFE' COHORT EXPERIENCE
Authors: [No Value] Huyen-Ly Nguyen, Mohammad A. Al-Freah, Roy Sherwood, Ivana Carey, Dorothy Joe, Abid Suddle, Phillip M. Harrison, Kosh Agarwal
Journal: Hepatology (2011)
Evolocumab Added to Statins to Reduce Progression of Coronary Atherosclerosis
Authors: Mohammad Alkhalil, Robin P. Choudhury
Journal: JAMA (2017)

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P08.51 Age-associated and therapy-induced alterations in the cellular microenvironment of experimental gliomas
Authors: H. Schneider, B. Lohmann
Journal: Neuro-Oncology (2017)

The poor prognosis associated with advanced age in patients with glioblastoma remains poorly understood. Glioblastoma in the elderly has been particularly associated with vascular endothelial growth factor (VEGF)-dependent angiogenesis, with anti-angiogenic agents such as the VEGF antibody, bevacizumab (BEV) reported to be preferentially active in this patient population. Here we explored host age-dependent differences in survival and benefit from radiotherapy (RT) or anti-angiogenic therapy in syngeneic mouse glioma models. Survival was inferior in older mice in the SMA-540 and SMA-560, but not in SMA-497 or GL-261 models. Detailed flow cytometric studies of early- and end-stage tumors revealed increased myeloid and decreased effector T cell population frequencies in SMA-540 tumors of old compared to young mice. In the SMA-540 model, bone marrow transplantation (BMT) from young to old mice had no effect, whereas survival was reduced with BMT from old to young mice. BEV significantly decreased vessel densities in gliomas of old mice, which correlated with survival, since old but not young SMA-540 tumor-bearing mice benefited from BEV alone, especially when combined with irradiation. Flow cytometric studies revealed that end-stage tumors of old mono- and co-treated mice exhibited increased infiltration of T helper and cytotoxic T cells compared to young mice. This model provides a powerful tool to evaluate the influence of host age on glioblastoma progression and treatment response and why co-treatment with VEGF inhibition and irradiation may lead to improved tumor control preferentially in glioblastoma of the elderly.
Phase II study of subcutaneous alemtuzumab (Campath-1H) therapy of patients with previously untreated chronic lymphocytic leukemia (CLL).
Authors: J Lundin, E Kimby, M Bjorkholm, F Celsing, G Hale, V Hjalmar, M Merup, A Petrescu, O Tullgren, H Waldmann, H Mellstedt, A Osterborg
Journal: Blood (2001)
Exposure of patients to ionising radiation during lung cancer diagnostic work-up
Authors: Robert C Rintoul, Rachel Atherton, Katharine Tweed, Stuart Yates, Edwin R Chilvers
Journal: Thorax (2017)

We examined the dose of radiation received during diagnosis of lung cancer as this may add to the risk of a second primary cancer. Patients undergoing surgery (n=40) or (chemo)radiotherapy (n=40) received comparable doses (28.6 and 25.8 mSv, respectively), significantly higher than that for supportive care (n=40; 15.1 mSv). The effective dose of radiation received was higher for early stage disease than for those with metastatic disease. The mean lifetime attributable risk of malignancy for those receiving treatment with curative intent in our cohort was 0.059%, and lung-specific risk 0.019%.
Abstract B44: Keratin-associated protein 5-5 controls cytoskeletal function and cancer cell vascular invasion
Authors: Eric B. Berens, Ghada M. Sharif, Marcel O. Schmidt, Casey W. Shuptrine, Louis M. Weiner, Eric Glasgow, Anna T. Riegel, Anton Wellstein
Journal: Cancer Research (2016)

Abstract Cancer cell vascular invasion is a crucial step in the malignant progression towards metastasis. Here we used a genome-wide RNAi screen with E0771 mammary cancer cells to uncover drivers of endothelial monolayer invasion. We identified keratin-associated protein 5-5 (Krtap5-5) as a candidate. Krtap5-5 belongs to large family of cysteine-rich proteins that is implicated in crosslinking keratin intermediate filaments during hair formation. To date, no role of these proteins in cancer has been reported. We found that depletion of Krtap5-5 from cancer cells led to cell blebbing, a loss of keratins 14 and 18 in addition to the upregulation of vimentin intermediate filaments. Krtap5-5 depletion did not impact cell viability but reduced cell motility and extravasation of cancer cells into tissues in a zebrafish model of extravasation. We conclude that Krtap5-5 is a previously unknown regulator of cytoskeletal function in cancer cells that modulates cell motility and vascular invasion. Citation Format: Eric B. Berens, Ghada M. Sharif, Marcel O. Schmidt, Casey W. Shuptrine, Louis M. Weiner, Eric Glasgow, Anna T. Riegel, Anton Wellstein. Keratin-associated protein 5-5 controls cytoskeletal function and cancer cell vascular invasion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B44.
US doctors are charged with female genital mutilation for first time
Authors: Owen Dyer
Journal: BMJ (2017)

Two Michigan doctors have been charged under a 1996 US federal law against female genital mutilation (FGM), the first people in the US to face such charges.

Jumana Nagarwala, 44, is accused of mutilating two Minnesota girls aged 7 who were brought to her by their parents.

FBI agents later arrested Fakhruddin Attar, 53, also a physician and the owner of the Detroit clinic where Nagarwala allegedly performed the mutilations. His wife, Farida Attar, who is not a physician, is accused of assisting Nagarwala in the procedure. The Attars are both charged with conspiracy to commit FGM.

Nagarwala was denied bail last week, before the Attars’ arrest. “There is clear and convincing evidence that she …