tbuckley/cabot-search huggingface dataset:
Effect of continuation of bevacizumab following disease progression in patients with metastatic colorectal cancer on survival
Authors: G. F. Samelis, A. Tsiakou, M. Karamanidi, M. Pelechrini, A. Zaganides, K. Ekmektzoglou
Journal: Journal of Clinical Oncology (2009)

e15143 Background: The management of patients with metastatic colorectal cancer (mCRC) has evolved dramatically over the last decade, with several “targeted” agents having entered the treatment arena. Multiple-line treatment is now considered as an important step towards the optimal therapeutic strategy for this patient population. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown clinical activity in patients with mCRC when used either as a first-line or second-line treatment. Currently, there is limited information in the literature on the use of bevacizumab combination chemotherapy in multiple lines with regimens including irinotecan and oxaliplatin, in mCRC patients who have progressed. Methods: We evaluated the efficacy and safety of bevacizumab in combination with standard chemotherapy (irinotecan, capecitabine, oxaliplatin, cetuximab) in 21 patients with metastatic colorectal cancer with a median age of 69 (range: 47–85) years old with PS: 0–1, included in the study. The metastatic sites were liver in 13 patients, liver and lung in 4 patients, lung in 2 patients, intra-abdominal in 1 patient and urinary-bladder in 1 patient. Bevacizumab treatment was continuously dispensed after disease progression and only other combined drugs were altered. Subgroup analysis was performed in terms of age, site of metastases, spread and co-morbidity. Results: The median age of the patients included in the analysis was 69 years (range 47–85). Progression free survival (PFS) was 17 months in first line setting (overall survival (OS) not reached yet) o, and for the age group &gt;69 and &lt;69 it was 23 and 16 months respectively (p=0.4565). Overall survival for the &lt;69 years old was 36 months. Anemia (all grades) was reported in 90.6% of the patients, while hemorrhage and thrombosis were reported in 28.6% and 14.3% respectively. Conclusions: Multiple line treatment in advanced colorectal cancer, including bevacizumab combined with standard chemotherapy, may improve OS (median: 23+ months) with an acceptable toxicity profile in patients with mCRC. However, further research through well-designed randomized studies is warranted to appraise the beneficial risk- benefit ratio of such an approach. No significant financial relationships to disclose.
Adhesion of Hematopoietic Progenitor Cells to Human Mesenchymal Stromal Cells as a Model for Interaction between Stem Cells and Their Niche.
Authors: Wolfgang Wagner, Frederik Wein, Christoph Roderburg, Vladimir Benes, Anke Diehlmann, Ulf Krause, Maria Frankhauser, Patrick Wuchter, Eckstein Volker, Anthony D. Ho
Journal: Blood (2006)
Evaluating Glucocorticoids for Sepsis
Authors: Sachin Yende, B. Taylor Thompson
Journal: JAMA (2016)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
A girl with left wrist deformity
Authors: Yong-Hai Zhou, Ming-Hua Zheng
Journal: BMJ (2016)

A 16 year old girl presented to the orthopaedic clinic with a deformed left wrist from birth. The girl had progressively increasing pain in the left wrist, and dorsiflexion was limited. On examination, she has a bayonet deformity of the left wrist, which leads to loss of grip strength, decreased extension, and supination. There were no other external congenital deformities. Anteroposterior and lateral radiographs of the left …
Emetic potential of daily oral etoposide
Authors: S. M. Herbert, M. J. Brames, L. H. Einhorn
Journal: Journal of Clinical Oncology (2006)

18618 Background: Chemotherapy agents are classified by their degree of emetogenicity. Agents with high or moderate emetogenicity are treated with a 5HT3 antagonist + dexamethasone to mitigate acute and delayed chemotherapy-induced nausea and vomiting. Intravenous etoposide (E) has low probability of nausea and/or vomiting. However, at the 2004 Perugia International Antiemetic Consensus meeting, oral E was listed as a moderately emetogenic drug (Supp Care Cancer 13:80–84, 2005). Daily oral E has been used to treat refractory germ cell cancer. We prospectively evaluated the emetic potential of daily oral etoposide in this patient (pt.) population. Methods: Between 8/03 and 12/05, 13 male pts. with refractory germ cell cancer were treated with single agent daily oral E 50 mg/M 2 day × 21 days every 4 weeks. All had progressed following cisplatin combination chemotherapy and had previously received high dose chemotherapy with carboplatin + E (intraveneously) with peripheral blood stem cell transplant. Median age was 35 (range 14 to 54). No pt. received prophylactic antiemetics. Pts. completed a 6 question Multinational Association Supportive Care Cancer (MASCC) antiemetic tool each day they received E. Intensity and duration of nausea were recorded, with 0 being none and 10 being most severe. Additionally, pts. were asked if they experienced vomiting. The number of vomiting episodes as well as any antiemetic medications were recorded. Data on 25 pts. will be presented and we currently have information on 13 pts. Results: 13 pts. completed the MASCC form. Only 2 pts. required antiemetic support. 1 pt. experienced emesis × 1 on day 1 and 1 pt. experienced emesis × 1 on day 11. 1 pt. experienced nausea on days 9 through 20 with a MASCC rating of 3–6. 1 pt. documented nausea day 1 through 21 with a MASCC rating of 1–3. 2 pts. experienced a MASCC rating of 1 of their nausea, 1 pt. on day 1 and 1 pt. on day 2. Overall, 8 of 13 pts. had no nausea or vomiting despite the absence of any antiemetics and 2 other patients had only minimal nausea for a single day. Conclusions: Daily oral E has only a low probability of emesis and does not require prophylactic antiemetics. [Table: see text]
Predictors of treatment choice in high risk and metastatic melanoma: evidence from the SEER-Medicare linked database
Authors: U. Iloeje, K. L. Davis, D. Mitra, S. Kotapati
Journal: Journal of Clinical Oncology (2008)

17511 Background: Knowledge about factors influencing treatment (tx) choice in advanced melanoma may prove informative in the provision of optimal care. These factors have not been examined using administrative data from real-world clinical settings. We analyzed retrospective claims data to evaluate predictors of 4 key tx options (surgery, radiation, chemotherapy, immunotherapy), as well as no active tx, in Medicare enrollees with high-risk (stage IIB/C, IIIA/B, IIIC) or metastatic (stage IV) melanoma. Methods: Data were from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database combining clinical information on incident cancer cases in the US from 1991 to 2002 with longitudinal (1991–2005) Medicare claims. Inclusion criteria were: age ≥65; ≥1 stage IIB or higher melanoma diagnosis; ≥6 months of continuous benefits coverage post-diagnosis. Separate multivariate logistic regressions were estimated for 4 non-mutually exclusive dichotomous indicators, each defined as receipt of the respective tx at any point post-diagnosis. A logistic model was also estimated for receipt of none of the noted therapies (i.e., no active tx). Results: 6,470 subjects met all inclusion criteria. Stage distribution was: IIB/C (37.6%); IIIA/B (45.9%); IIIC (1.4%); IV (15.2%). Median follow-up was 40 months and 61% were male. The most prevalent tx was surgery (received by 91% of subjects), followed by radiation (24%), chemotherapy (20%), and immunotherapy (8%). Older age was associated with a higher probability of no active tx. Other predictors of no tx were being in the South [odds ratio=2.03; 95%CI=(1.36–3.03)], higher comorbidity burden [1.06(1.02–1.10)], and stage IV disease [5.11(3.91–6.67)]. Race had no effect on tx choice, but males were more likely to receive radiation and chemotherapy. Stage IV disease was associated with reduced odds of surgery [0.09(0.07–0.11)] and higher odds of radiation [4.32(3.64–5.13)], chemotherapy [2.31(1.91–2.79)], and immunotherapy [4.43(3.18–6.16)]. Conclusions: Our study documents factors influencing tx choice in a representative population of elderly patients with high risk or metastatic melanoma. Age, comorbidity burden, and disease stage were important factors for all therapeutic choices. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Orally administrative melk (maternal embryonic leucine zipper kinase)-targeting small molecule inhibitor suppresses the growth of various types of human cancer.
Authors: Suyoun Chung, Hanae Suzuki, Takashi Miyamoto, Naofumi Takamatsu, Ayako Tatsuguchi, Koji Ueda, Kyoko Kijima, Yo Matsuo, Yusuke Nakamura
Journal: Journal of Clinical Oncology (2013)

e13569 Background: We previously reported MELK (maternal embryonic leucine zipper kinase) as a novel therapeutic target for breast cancer. MELK was also highly upregulated in multiple types of cancer including prostate, pancreas and lung cancers, and plays indispensable roles in cancer cell survival, particularly in the maintenance of tumor-initiating cells. In this study, we attempted to identify novel substrates of MELK and develop the small-molecule MELK inhibitor. Methods: To elucidate the MELK signaling pathway in breast cancer cells, we screened MELK substrates by 2D-PAGE and mass spectrometric analysis, and characterized two of them for their roles in mammary carcinogenesis. Furthermore, we conducted a high-throughput screening of a compound library followed by structure-activity relationship studies. We investigated the growth suppressive effect of a MELK inhibitor OTSSP167 using xenograft models in mice and a mammosphere-formation assay. Results: We identified two novel MELK substrates, DBNL and PSMA1, which plays critical roles in invasiveness of cancer cells and maintenance of mammary tumor-initiating cells. We successfully obtained a highly potent MELK inhibitor OTSSP167 with IC 50 of 0.41 nM. OTSSP167 inhibited the phosphorylation of these two substrates by MELK as well as mammosphere formation of breast cancer cells, and exhibited strong tumor-growth suppressive effects on xenografts of human breast, lung, prostate, and pancreas cancer cell lines in mice by both intravenous and oral administration. Conclusions: Orally administrative MELK inhibitor OTSSP167 is a promising compound to treat various types of human cancer. This compound can inhibit the phosphorylation of MELK substrates and also suppresses the formation of cancer stem cells in breast cancer cells, providing a novel strategy to cure cancer.
Laminar Module Cascade from Layer 5 to 6 Implementing Cue-to-Target Conversion for Object Memory Retrieval in the Primate Temporal Cortex
Authors: Kenji W. Koyano, Masaki Takeda, Teppei Matsui, Toshiyuki Hirabayashi, Yohei Ohashi, Yasushi Miyashita
Journal: Neuron (2016)
Epidermal growth factor receptor (EGFR), cyclooxygenase-2 (COX-2), and cyclin D1 expression in squamous cell carcinoma of the anal canal.
Authors: S. Yunus, C. Lobocki, J. Cattoni, B. Silberberg, A. Drelichman
Journal: Journal of Clinical Oncology (2010)

e21095 Background: Identification of proteins overexpressed in squamous cell carcinoma of the anal canal will increase our understanding of the biology of these uncommon tumors, and may help to identify potential new therapeutic targets. Cetuximab, a monoclonal antibody that targets EGFR, is used in the treatment of head and neck squamous cell tumors, which frequently express this receptor. COX-2 activity and Cyclin D1 amplification have also been seen in other squamous cell carcinomas, but their role in anal cancers has not been well studied. The purpose of this study was to examine the expression of these proteins in squamous cell tumors of the anal canal. Methods: Twenty cases of invasive squamous cell carcinoma of the anal canal were examined immunohistochemically for expression of COX-2, EGFR and Cyclin D1. Tumor cells were graded based on the intensity of staining, and expression was considered positive when > 10% of cells were stained (1-3+). Protein expression was correlated with tumor histology and other clinical variables. Results: The majority of tumors (19/20; 95%) stained positive for COX-2 and EGFR. Moderate to intense staining (2-3+) was observed in 75% and 45% of tumor tissues for COX-2 and EGFR, respectively. Fifty percent of these tumors were also positive for Cyclin D1, with the majority exhibiting a moderate staining pattern. Interestingly, the most intense staining for each of these markers was observed in the more actively proliferating basal layer of cells, especially in the keratinized sub-type. In addition, keratinized tumors exhibited more intense COX-2 expression (10/11; 90.9%) than non-keratinized tumors (5/9; 55.6%). No associations were found between tumor grade or Cyclin D1 expression and other variables. However, all four patients identified with positive lymph node status exhibited moderate to intense staining for both EGFR and COX-2. Conclusions: Since EGFR and COX-2 are expressed in the majority of squamous cell anal cancers, the role of EGFR-targeted therapies and COX-2 inhibitors in the treatment of these tumors should be further investigated. No significant financial relationships to disclose.
Early Education Programs for Low-Income Children
Authors: Michael Silverstein, Caroline J. Kistin
Journal: JAMA Pediatrics (2016)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Correlation of hexokinase-2 expression with overall survival and potential as a therapeutic target in the treatment of breast cancer brain metastases
Authors: S. M. Shreeve, D. Palmieri, M. M. Johnson, K. D. Aldape, S. Davis, P. S. Meltzer, G. L. Davis, C. M. Hoffmann, S. M. Steinberg, P. S. Steeg
Journal: Journal of Clinical Oncology (2008)

1005 Background: The prevalence of brain metastasis from breast cancer (BCA) is increasing. We have identified several potential therapeutic targets through gene expression profiling of human BCA brain metastases. One potential target, hexokinase II (HK-2), is up-regulated in brain metastases as compared to unlinked primary tumors. HK-2 plays a vital role in the generation of many components required for cell growth and inhibits apoptosis through mitochondrial binding. We hypothesized that HK-2 promotes metastatic cell proliferation in the brain and that its increased expression would negatively impact patient survival post-resection. Methods: The gene expression profile of surgically resected human BCA brain metastases was compared to that of non-related unlinked primary invasive ductal carcinomas using cDNA microarray analysis. In a separate retrospective study, we generated survival curves dividing a cohort of 113 patients based on HK-2 immunoreactivity in resected brain metastases. To evaluate the functional role of HK-2, a human BCA cell subline that is selectively metastatic to the brain (MDA-MB-231BR) in a xenograft model was used. Cells were transduced using VSV-g pseudotyped lentiviral particles carrying shRNA targeting either HK-2 or a non-target control (Sigma-Aldrich). Results: Significance of microarray analysis identified several genes with differential expression between brain metastases and unlinked primary BCA tumors. HK-2 was up-regulated in brain metastases, and this was validated by QRT-PCR which showed a 2-fold up-regulation in brain metastases compared to unmatched primaries (n=8, p=0.01). Retrospective analysis showed that median survival for patients (n=94) with a high level of HK-2 expression in resected brain metastasis was 9.6 months post-surgery as compared to 17.5 months in patients (n=19) with a low level of HK-2 (p=0.0275). Knockdown of HK-2 expression by 95% inhibited MDA-MB-231BR proliferation by 40 % at five days under normal grwoth conditions (p=0.0012). Conclusions: These data suggest that over-expression of HK-2 is associated with poorer overall patient survival post brain metastasis resection and that HK-2 plays a key role in the proliferation of metastatic cells in brain. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Sigma-Aldrich Sigma-Aldrich
Ruxolitinib Reduces Cytokine/Chemokine Levels and Improves Fatigue and Chronic Lymphocytic Leukemia (CLL)-Related Symptoms in CLL Patients Not Requiring Systemic Therapy
Authors: Preetesh Jain, Michael J. Keating, Charles Cleeland, Sarah Renner, Huang Xuelin, Graciela Nogueras Gonzalez, David M. Harris, William Wierda, Courtney DiNardo, Naveen Pemmaraju, Nitin Jain, Philip Thompson, Alessandra Ferrajoli, Jan A. Burger, Hagop M. Kantarjian, Srdan Verstovsek, Zeev Estrov
Journal: Blood (2015)
Outcome with total therapy 3 (TT3) compared to total therapy 2 (TT2): Role of GEP70-defined high-risk disease with trisomy of 1q21 and activation of the proteasome gene <i>PSMD4</i>.
Authors: J. D. Shaughnessy, P. Qu, E. Tian, R. Edmondson, B. P. Nair, S. Waheed, Y. Alsayed, F. Van Rhee, J. Haessler, J. Crowley, B Barlogie
Journal: Journal of Clinical Oncology (2010)

8027 Background: A GEP-based risk model (GEP70) defines 15% of newly diagnosed MM with a median survival of 2yr compared to 10+yr others. GEP70 is driven by elevated expression of genes from chromosome 1q and FISH-defined gains of 1q21. In serial studies, low risk frequently evolves to high-risk with increased amplification of 1q21. PSMD4, regulatory subunit of the proteasome, is one of only two genes in the 70GEP model that map to the 1q21 amplicon. We hypothesized that the sensitivity of MM cells to BOR-induced apoptosis might depend on copy-number driven activity of PSMD4. Methods: In TT3, we added BOR to TT2 and performed GEP at baseline and 48hr after 1.0mg/m2 BOR. We correlated GEP and 1q21 FISH with outcomes in over 600 cases. Results: PSMD4 and 14 other proteasome genes were among 80 genes whose post-BOR elevated expression was related to poor outcome. PSMD4 and proteasome genes were not activated by thalidomide, dexamethasone or lenalidomide suggesting that this effect was BOR-specific. There was strong but not complete overlap between risk designations by the GEP70 and GEP80 models in TT2 and TT3. We combined the risk predictions creating four risk catagories. Kaplan Meier analysis revealed a dramatic improvement in outcomes of GEP70 high-risk/GEP80 low-risk cases in TT3 relative to TT2. Similarly, disease with 3 copies of 1q21, but not disease with 2 or 4+ copies experienced improved outcomes. We correlated expression of candidate genes with the presence of 2, 3 or 4+ copies of 1q21 and found that intermediate levels of PSMD4, corresponding to disease with 3 copies of 1q21, was associated improved outcomes in TT3. Conclusions: PSMD4, a copy number dependent gene at 1q21, is a strong prognostic biomarker in MM. Modest increases in PSMD4 gene expression, conferring a poor prognosis in TT2 is overcome by BOR in TT3. We speculate that dose limiting toxicities of BOR may interfere with the ability of this drug to kill MM cells with 4+ copies of 1q21. Novel therapeutic strategies over coming this BOR limitation may be needed to improve the dismal survival associated with high-level amplification of 1q21. No significant financial relationships to disclose.
Psoriasis, fracture risk and bone mineral density: the HUNT Study, Norway
Authors: E.H. Modalsli, B.O. Åsvold, P.R. Romundstad, A. Langhammer, M. Hoff, S. Forsmo, L. Naldi, M. Saunes
Journal: British Journal of Dermatology (2016)

An association between psoriasis and osteoporosis has been reported. To investigate, in a large prospective population‐based Norwegian study, whether psoriasis is associated with increased risk of forearm or hip fracture; to investigate the cross‐sectional association between psoriasis and bone mineral density (BMD) T‐score in a subpopulation. Hospital‐derived fracture data from Nord‐Trøndelag County (1995–2013) were linked to psoriasis information, BMD measurements and lifestyle factors from the third survey of the Nord‐Trøndelag Health Study 2006–08 (HUNT3); socioeconomic data from the National Education Database; and use of medication from the Norwegian Prescription Database. Among 48 194 participants in HUNT3, we found no increased risk of forearm or hip fracture in 2804 patients with self‐reported psoriasis [overall age‐ and sex‐adjusted hazard ratio 1·03, 95% confidence interval (CI) 0·82–1·31]. No clear association was found between psoriasis and mean BMD T‐score; overall age‐ and sex‐adjusted differences in total hip, femoral neck and lumbar spine BMD T‐scores were 0·02 (95% CI −0·11 to 0·14), 0·05 (95% CI −0·06 to 0·17) and 0·07 (95% CI −0·09 to 0·24), respectively. No clear association was found between psoriasis and prevalent osteoporosis in either total hip, femoral neck or lumbar spine; overall age‐ and sex‐adjusted odds ratio was 0·77 (95% CI 0·54–1·10). Associations did not change substantially after adjustment for education, smoking, systemic steroid use and body mass index. We found no association between psoriasis and risk of fracture. The study did not indicate reduced BMD T‐score or higher prevalence of osteoporosis among patients with psoriasis.