tbuckley/cabot-search huggingface dataset:
Enhanced Therapeutic Index of Radioimmunotherapy (RIT) in Prostate Cancer Patients
Authors: Sally J. DeNardo, Gerald L. DeNardo, A. Yuan, Carol M. Richman, Robert T. O’Donnell, Primo N. Lara, David L. Kukis, Arutselvan Natarajan, Kathleen R. Lamborn, Frederik Jacobs, Christine L. Hartmann Siantar
Journal: Clinical Cancer Research (2003)

Purpose: Radioimmunotherapy delivered by radiometal immunoconjugates and followed by marrow support is dose limited by deposition of radioactivity in normal organs. To increase elimination of radioactivity from the liver and body and, thus, minimize hepatic radiation dose, a peptide having a specific cathepsin B cleavage site was placed between the radiometal chelate DOTA (1,4,7,10-tetraazacyclododecane- N , N ′, N ″, N ‴-tetraacetic acid) and the monoclonal antibody m170, and the comparative pharmacokinetics was evaluated in prostate cancer patients.

Experimental Design: 111In-DOTA-2IT-m170 and 111In-DOTA-peptide-(GGGF)-m170, representing the same monoclonal antibody and chelate with and without the cleavable linkage, were studied in comparable groups of prostate cancer patients (17 with In-2IT-BAD-m170 and 8 with In-DOTA-peptide-m170). Pharmacokinetics over 7 days, calculated yttrium-90 radiation dosimetry, therapeutic index, and projected maximum tolerated injected yttrium-90 dose were evaluated.

Results: The radioimmunoconjugates pharmacokinetics and calculated tumor and normal organ absorbed radiation dose (rads/mCi) were similar, except for a significant decrease in the mean dose to the liver (31%; P < 0.01) and lungs (31%; P < 0.01) with the DOTA-peptide immunoconjugates. Because mean tumor dose was not statistically different, this peptide linkage provided a significant increase in the therapeutic index for this tumor targeting radiopharmaceutical. If marrow support is adequate, the radiation dose historically tolerated by normal organs other than marrow would allow a 30% increase in the administered dose, resulting in a mean dose of 9500 rads to metastatic prostate cancer.
Endoscopic septotomy of a magnet-induced neoseptum in a large mid-esophageal diverticulum
Authors: Selcuk Disibeyaz, Fatih Saygili, Erkin Oztas, Orhan Coskun
Journal: Endoscopy (2016)

A 72-year-old man who was complaining of dysphagia, regurgitation, and difficulty with passage through the esophagus was diagnosed with a mid-esophageal diverticulum with a diameter of 40 mm. A contrast esophagogram ([Fig. 1]), a computed tomography (CT) scan ([Fig. 2]), and an endoscopic examination revealed that the diverticulum had a narrow neck and was filled with food particles. Because of the patient's age and comorbidities, which included coronary heart disease and hypertension, and his reluctance to undergo major surgery, non-surgical treatment options were explored. Inspired by a mini-series involving three cases [1], we attempted to use magnets to perform a fusion between the esophageal wall and the wall of the diverticula to induce a neoseptum. Once the neoseptum had been formed, it would be possible to perform septotomy with electrocautery and to widen the narrow neck so that food could washout easily, thereby avoiding obstructive symptoms.
Abstract 5087: EMT in cancer cells promotes the extracellular matrix remodeling by cancer-associated fibroblasts
Authors: Shinya Neri, Genichiro Ishii, Atsushi Ochiai, Toshi Menju, Makoto Sonobe, Hiroshi Date
Journal: Cancer Research (2016)

Abstract Microenvironmental factors in tumor tissue induce epithelial-mesenchymal transition (EMT) in cancer cells. However, it remains unclear how EMT-induced cancer cells affect mechanisms of invasion by cancer-associated fibroblasts (CAFs). In this study, we investigated how EMT-induced cancer cells develop supportive functions of CAFs in the process of local invasion. Using an in vitro collagen invasion assay model, EMT-induced cancer cells invaded the collagen matrix to a greater extent compared to control cells when they were cultured alone. Interestingly, CAFs co-cultured with EMT-induced cancer cells invaded to a greater extent compared to those with control cancer cells. We revealed that platelet-derived growth factor (PDGF)-B was upregulated in EMT-induced cancer cells, and the invasion ability of CAFs decreased by shRNA knockdown of PDGF-B in EMT-induced cancer cells. Treatment of a PDGF receptor inhibitor cancelled the increased invasion abilities of CAFs and EMT-induced cancer cells. Our results indicated that EMT-induced cancer cells enhanced the CAF invasion ability through the secretion of PDGF-BB as well as increased the invasion ability themselves, suggesting that EMT-induced cancer cells in the tumor microenvironment could not only exhibit their increased invasion but also promote CAF invasion which might lead to local invasion of cancer cells. Citation Format: Shinya Neri, Genichiro Ishii, Atsushi Ochiai, Toshi Menju, Makoto Sonobe, Hiroshi Date. EMT in cancer cells promotes the extracellular matrix remodeling by cancer-associated fibroblasts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5087.
Abstract 3539: Vitamin D/EB 1089 mediated radio-sensitization of lung cancer cells and head and neck cancer cells
Authors: Theresa Thekkudan, Khushboo Sharma, Tareq Saleh, David Gewirtz
Journal: Cancer Research (2016)

Abstract Lung cancer is a principal factor contributing to cancer-related mortality in the United States. Patients with lung cancer generally have a poor prognosis and resection is often not possible. Our previous work has demonstrated that Vitamin D and its analog, EB1089 (EB), enhance radio sensitivity of H460 and A549 non-small cell lung cancer (NSCLC) cells (Sharma et al; A novel cytostatic form of autophagy in sensitization of non-small cell lung cancer cells to radiation by vitamin D and the vitamin D analog, EB 1089. Autophagy; 2014;10(12):2346-61). In this study, we have extended these findings of Vitamin D/EB 1089 induced radio-sensitization in multiple tumor cell lines such as Lewis Lung mouse non-small cell lung cancer cells (LLC), head and neck cancer cells (HN30) and a primary cell line established from a lung tumor obtained from a cancer patient. All cell lines were treated with multiple doses of radiation in the range of 2-6 Gy and EB1089 was used at concentration of 100nM. Sensitivity was determined based on viable cell number and clonogenic survival. We observed enhanced radiation sensitivity of LLC and HN30 cells with the combination treatment of radiation and EB1089. However, as reported previously by our laboratory (Sharma et al., 2014; Autophagy), sensitization was dependent on the presence of functional p53 and was not evident in HN6 head and neck tumor cells that are mutant in p53. These data suggest that Vitamin D or a Vitamin D analog could be used to enhance radiation sensitivity of various malignancies but only where the tumors express wild type p53. Furthermore, we were able to demonstrate sensitization in a primary cell line established from lung tumor tissues utilizing conditioned medium from stromal cells treated with EB1089. These data suggest that stromal re-programming of cancer cells could influence radiation sensitivity. In studies to define the signaling pathways associated with radiation sensitization, we also observed inactivation by EB 1089 of the NF-kB pathway that was activated by radiation alone in H460 and H1299 NSCLC cells. Silencing of AMPK attenuated radiation sensitization by EB 1089. Sensitization was accompanied by enhanced secretion of the autophagy/senescence related marker, HMGB1. Taken together, these studies indicate that Vitamin and/or its analogs enhance radiosensitivity by cellular pathways involving NF-kB and AMPK and that HMGB1 may be secreted to activate an immune response to the combination treatment. Citation Format: Theresa Thekkudan, Khushboo Sharma, Tareq Saleh, David Gewirtz. Vitamin D/EB 1089 mediated radio-sensitization of lung cancer cells and head and neck cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3539.
A multinational, randomized, phase III trial of XELIRI (+bevacizumab) versus FOLFIRI (+bevacizumab) as the second-line chemotherapy for metastatic colorectal cancer: Asian XELIRI project (AXEPT).
Authors: Kei Muro, Tae Won Kim, Young Suk Park, Hiroyuki Uetake, Tomohiro Nishina, Hiroaki Nozawa, Hiroshi Matsumoto, Kentaro Yamazaki, Sae-Won Han, Keun-Wook Lee, Yanhong Deng, Marc E. Buyse, Taroh Satoh, Baek-Yeol Ryoo, Lin Shen, Satoru Iwasa, Satoshi Morita, Junichi Sakamoto, Rui-hua Xu
Journal: Journal of Clinical Oncology (2016)

TPS780 Background: Life-prolonging systemic therapy such as chemotherapy (FOLFOX, XELOX, FOLFIRI, 5-FU/LV) with / without molecular targeted agents (bevacizumab, afilibercept, cetuximab, panitumumab) are important treatment for metastatic colorectal cancer (mCRC). On the other hand, it is required to establish an evidence of convenient therapy including oral anticancer agent which is expected lower risk of safety. XELIRI was already examined by various doses in this decade, and result of AIO 0604 was regarded as one of the most appropriate regimen. The BIX phase II study showed the tolerability and promising efficacy of the AIO regimen for Japanese mCRC patients (Hamamoto Y, et al. Oncologist 2014). Methods: Asian XELIRI Project (AXEPT) is an East Asian collaborated, open label, randomized phase III clinical trial designed to demonstrate the non-inferiority of XELIRI (+bevacizumab) to the standard of care FOLFIRI (+bevacizumab) as the second-line chemotherapy in patients with mCRC. The primary endpoint is median overall survival. The secondary endpoints are progression-free survival, time to treatment failure, overall response rate, disease control rate, relative dose intensity, safety, correlation between UGT1A1 polymorphisms (*28, *6) and safety. Eligible patients were 20 years of age and older, had histologically proven CRC, ECOG performance status 0-2, adequate organ function, progression or difficult to continue after first line regimen. Patients were randomized 1:1 to standard FOLFIRI (+bevacizuamb 5mg/kg day1), repeated every 14 days (Group A) or XELIRI, Irinotecan 200mg/m2 day1, and capecitabine 1600mg/m2 day 1-14 (+bevacizumab 7.5mg/kg day1), repeated every 21 days (Group B). A Total of 464 events were needed to show non-inferiority with a two-sided α of 0·05 and a power of 80%, a target sample size of 600 patients was required. (The 95% CI upper limit of the hazard ratio was pre-specified as less than 1.3.). Enrollment has started in December 2013. As of August 2015, 98 centers in the Japan, South Korea and China are participating in this trial. Clinical trial information: NCT01996306. UMIN000012263. Clinical trial information: NCT01996306.
Prevalence and Prognostic Significance of PTEN Loss in African-American and European-American Men Undergoing Radical Prostatectomy
Authors: Jeffrey J. Tosoian, Fawaz Almutairi, Carlos L. Morais, Stephanie Glavaris, Jessica Hicks, Debasish Sundi, Elizabeth Humphreys, Misop Han, Angelo M. De Marzo, Ashley E. Ross, Scott A. Tomlins, Edward M. Schaeffer, Bruce J. Trock, Tamara L. Lotan
Journal: European Urology (2016)
Exercise and Hypertension
Journal: JAMA (1995)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 3218: Disruption of the CD39 immune checkpoint pathway increases the efficacy of various anticancer therapies in syngeneic mouse models
Authors: Marion Lapierre, Cécile Dejou, Carine Paturel, Henri-Alexandre Michaud, Laurent Gros, Armand Bensussan, Jean-François Eliaou, Jeremy Bastid, Nathalie Bonnefoy
Journal: Cancer Research (2016)

Abstract The CD39-CD73-adenosine pathway is an emerging regulator of the immune antitumor response. CD39 is expressed within tumors and the tumor microenvironment by several cell population including immune and cancer cells. In tumor tissues, the pathway leads to the accumulation of immunosuppressive adenosine together with decreased levels of immunoactivating peritumoral ATP. We reported previously that CD39 blockade increased T cell and NK cell-mediated cytotoxic activity in vitro and disclose, during this meeting, the development of the first human-CD39-blocking humanized antibody (S. Augier et al., Preclinical development of a humanized blocking antibody targeting the CD39 immune checkpoint for cancer immunotherapy). Here we demonstrated that this pathway is involved in tumor-induced resistance to various cancer therapies in syngeneic mouse melanoma, colon cancer and fibrosarcoma models. We used therapy-resistant mouse models or inefficacious treatment regimens in the CD39 knockout mice to assess the capacity of CD39 to affect the response to chemotherapies, tumor associated antigen (TAA)-targeting antibodies and immunomodulators such as anti-PD1 antibodies. We achieved increased response rates, increased response duration and some complete and long lasting tumor regressions in the CD39 deficient context. These preclinical proof-of-concept studies highlight the role of the CD39 immune checkpoint pathway in limiting the efficacy of various anticancer therapies in syngeneic mouse models and thereby support the potential clinical value of the humanized CD39-neutralizing antibody under development. Citation Format: Marion Lapierre, Cécile Dejou, Carine Paturel, Henri-Alexandre Michaud, Laurent Gros, Armand Bensussan, Jean-François Eliaou, Jeremy Bastid, Nathalie Bonnefoy. Disruption of the CD39 immune checkpoint pathway increases the efficacy of various anticancer therapies in syngeneic mouse models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3218.
Abstract 822: Role of c-Myc in prostate cancer stem-like cell inhibition by sulforaphane
Authors: Su-Hyeong Kim, Avani R. Vyas, Shivendra V. Singh
Journal: Cancer Research (2016)

Abstract Chemopreventive efficacy of D,L-sulforaphane (SFN) against prostate cancer has been shown in a transgenic mouse model but the underlying mechanism is not fully understood. The present study demonstrates that c-Myc, which is an oncogenic transcription factor frequently upregulated in human prostate cancer, is a molecular target of SFN. Exposure of human prostate cancer cells (LNCaP, C4-2, and PC-3) and a cell line derived from prostate adenocarcinoma of a transgenic mouse (Myc-CaP) to SFN resulted in a marked decrease in c-Myc protein level. Naturally-occurring thio, sulfinyl, and sulfonyl analogues of SFN were also effective in causing suppression of c-Myc protein level. The c-Myc is a known regulator of cellular metabolism but basal glycolysis was not altered by SFN treatment in empty vector transfected or in c-Myc overexpressing PC-3 cells. The effect of SFN treatment on prostate cancer stem-like cells (pCSC) was also determined as c-Myc is implicated in their maintenance. Analysis of aldehyde dehydrogenase 1 activity, CD49f+ fraction, and sphere forming efficiency revealed dose-dependent inhibition of pCSC in SFN-treated cells. The pCSC inhibition by SFN was partially but significantly attenuated by overexpression of c-Myc. Expression profiling revealed upregulation of a set of stemness genes by c-Myc overexpression but their downregulation by SFN treatment. Finally, oral administration of SFN to Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice resulted in a marked decrease in c-Myc protein expression in the adenocarcinoma. In conclusion, this study indicates that c-Myc downregulation contributes to pCSC inhibition by SFN. This investigation was supported by grant CA115498 awarded by the National Cancer Institute. Citation Format: Su-Hyeong Kim, Avani R. Vyas, Shivendra V. Singh. Role of c-Myc in prostate cancer stem-like cell inhibition by sulforaphane. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 822.
Estimation of Evolutionary Distance between Distantly Related Sequences of Amino Acids, Taking Account of Patterns of Amino Acid Replacement)
Authors: Kaoru Fukami-Kobayashi, Kaoru Fukami-Kohay- Ashi
Journal: Molecular Biology and Evolution (1994)

When amino acid sequences are distantly related-for instance, when their identity is <0.30-it is difficult to estimate their evolutionary distance.A method called the "similarity distance method" (SD method) was developed to obtain maximum-likelihood estimates of evolutionary distance between amino acid sequences, on the basis of a given pattern of amino acid replacement.Computer simulation revealed that, by using the new method, evolutionary distance can be estimated efficiently even when the expected identity between the sequences is as low as 0.14 and the length of the sequences is only 50 amino acid residues.The new method is useful in phylogenetic analyses of distantly related and/or short sequences of amino acids, such as structural or functional domains commonly found in several proteins.
Chronic Myelomonocytic Leukemia in Young Patients: Molecular and Cytogenetic Predictors of Survival and Treatment Outcome
Authors: Mrinal M. Patnaik, Emnet A Wassie, Eric Padron, Francesco Onida, Raphael Itzykson, Terra L Lasho, Olivier Kosmider, Christy Finke, Curtis A. Hanson, Rhett Ketterling, Rami S Komrokji, Ayalew Tefferi, Eric Solary
Journal: Blood (2014)
Trends in Prevalence of Chronic Kidney Disease in the United States
Authors: Daniel Murphy, Charles E. McCulloch, Feng Lin, Tanushree Banerjee, Jennifer L. Bragg-Gresham, Mark S. Eberhardt, Hal Morgenstern, Meda E. Pavkov, Rajiv Saran, Neil R. Powe, Chi-yuan Hsu
Journal: Annals of Internal Medicine (2016)

Trends in the prevalence of chronic kidney disease (CKD) are important for health care policy and planning.To update trends in CKD prevalence.Repeated cross-sectional study.NHANES (National Health and Nutrition Examination Survey) for 1988 to 1994 and every 2 years from 1999 to 2012.Adults aged 20 years or older.Chronic kidney disease (stages 3 and 4) was defined as an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73 m2, estimated with the Chronic Kidney Disease Epidemiology Collaboration equation from calibrated serum creatinine measurements. An expanded definition of CKD also included persons with an eGFR of at least 60 mL/min/1.73 m2 and a 1-time urine albumin-creatinine ratio of at least 30 mg/g.The unadjusted prevalence of stage 3 and 4 CKD increased from the late 1990s to the early 2000s. Since 2003 to 2004, however, the overall prevalence has largely stabilized (for example, 6.9% prevalence in 2003 to 2004 and in 2011 to 2012). There was little difference in adjusted prevalence of stage 3 and 4 CKD overall in 2003 to 2004 versus 2011 to 2012 after age, sex, race/ethnicity, and diabetes mellitus status were controlled for (P = 0.26). Lack of increase in CKD prevalence since the early 2000s was observed in most subgroups and with an expanded definition of CKD that included persons with higher eGFRs and albuminuria.Serum creatinine and albuminuria were measured only once in each person.In a reversal of prior trends, there has been no appreciable increase in the prevalence of stage 3 and 4 CKD in the U.S. population overall during the most recent decade.American Society of Nephrology Foundation for Kidney Research Student Scholar Grant Program, Centers for Disease Control and Prevention, and National Institutes of Health.
Abstract 2846: Proliferative recovery after chemotherapy-induced senescence in non-small cell lung cancer (NSCLC) cells as a model of tumor dormancy and disease recurrence
Authors: Tareq Saleh, Theresa Thekkudan, Moureq R. Alotaibi, David A. Gewirtz
Journal: Cancer Research (2016)

Abstract Lung cancer is the leading cause of cancer-related death in both men and women in the United States. Most lung cancer cases are diagnosed in advanced, inoperable stages and are treated with chemoradiation; while chemoradiation is effective in suppressing tumor progression, recurrence following treatment is not infrequent. As there is no well-accepted preclinical model for tumor dormancy and disease recurrence, we hypothesize that the promotion of transient autophagy and senescence could be developed as a model of tumor growth and recovery following treatment. Studies were performed utilizing H460 NSCLC cells as well as a primary NSCLC cell line isolated and grown in our laboratory from a stage IV adenocarcinoma. After treatment with etoposide (1 uM), growth arrest was accompanied by the robust induction of autophagy and senescence. This growth arrest was transient and was followed by proliferative recovery in the course of several days. Genetic and pharmacological inhibition of autophagy failed to interfere with the ability of the cells to regrow, indicating a non-cytoprotective function of autophagy in response to etoposide (in contrast to the cytoprotective function of autophagy exhibited in response to radiation). Quantification of senescence over time based on C12FDG staining and flow cytometry demonstrated that the reversal of growth arrest coincided with a decline in the extent of senescence. To more precisely define the source of the recovered cells, senescent and non-senescent but growth arrested cells were separated by flow cytometry based on their relative β-galactosidase expression and replated. Both cell populations demonstrated the ability to re-emerge from the growth-arrested state and recover proliferative capacity. These observations suggest that senescence is ultimately a transient process in that at least a subpopulation of tumor cells can and will recover proliferative capacity. Furthermore, the reversibility of therapy-induced senescence (TIS) might prove to be a useful model both in cell culture and in vivo to study tumor dormancy and disease recurrence. Studies are currently in progress to determine the impact of senescence inhibition on tumor recovery as well as sensitivity to subsequent therapy given that recurrent disease tends to be relatively refractory to further treatment. Citation Format: Tareq Saleh, Theresa Thekkudan, Moureq R. Alotaibi, David A. Gewirtz. Proliferative recovery after chemotherapy-induced senescence in non-small cell lung cancer (NSCLC) cells as a model of tumor dormancy and disease recurrence. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2846.