tbuckley/cabot-search huggingface dataset:
The evidence base for the risk and management of thrombosis in hematological malignancies patients
Authors: F. M. Hassan
Journal: Journal of Clinical Oncology (2006)

16526 Background: To evaluate of hypercoagulable state and tumor procoagulant activity in hematological malignancies patients.To address the Primary thromboprophylaxis managed. Methods: Paper-based reply-paid questionnaire was distributed between patients, included the information about the duration, treatment used, sex, age, and type of malignant. We respectively analyzed 96 Patients male and female in all age groups treated for the prevention of recurrent venous thromboembolism in patients with hematological malignancies patients, against 33 (19–75 years, 15 male, 18 female) apparently healthy adults individual setting as control groups. The clinical analysis included thrombotic markers (protein S, protein C, PF1.2, TAT, PAI-1and fibrin D-dimer) were done to all patients and control. Low-molecular weight heparin (LMWH) versus Oral anticoagulant frequency distribution were compared between cases and controls using statistical analysis. Results: In total, 93 completed questionnaires were returned, respondents were reported the routine treatment of more than 10 types of haemopatopoietic and lymphoid tissues tumours. Of these, CML and CLL were most commonly treated (by 45%-62% of respondents), with lymphoma, plasma cell myeloma, AML, polythycythemia vera, and mast cell sarcoma the next most common (treated by 26%-38% of respondents). Most of patients (76%) showed a markedly elevation of PAI-1 and D-dimer and significantly elevated in whose treated Surgically, while the other thrombotic markers (protein S, protein C, PF1.2, TAT were normal compared to control groups. Conclusions: Thrombosis is a common complication in patients with haemopatopoietic and lymphoid tissues tumours that adversely affects their survival. There are several problems associated with the treatment of VTE in patients, especially with the use of oral anticoagulants. No significant financial relationships to disclose.
Breast cancer in the elderly.
Authors: Dilek Erdem, Bahiddin Yilmaz, Fatih Mehmet Cilingir, Selim Kocasarac, Fatih Teker, Guzin Gonullu, Idris Yucel
Journal: Journal of Clinical Oncology (2013)

e11506 Background: Breast cancer is one of the age-related tumors that accompany with population ageing and approximately 50 % of this disease occur in 65 years of age or older and also more than 30 % occur after age of 70. This study aims to examine characteristics of patients with breast cancer 65 years or older. Methods: The study was carried out on a series of 177 breast cancer patient followed up at our outpatient clinic who are 65 years or older chosen among 848 breast cancer patients during the period 1995-2012. Physical examination, annual chest x-ray, mammography, abdominal ultrasonography and bone scan were the tools to assess the disease status. SPSS 16 was used. Results: The mean age was 70.8 years old (range 65-85 years). There was only one patient whose age is older than 85 years. 85 % of histopathology was infiltratif ductal carcinoma. 83 % of patients underwent mastectomy while 92 % was performed axillary dissection. 56 % had node positivity and 54 % had 2 cm or bigger tumor. ER/PR status was both negative in 54 women (30 %) and both positive in 82 of them. Also cerbB2 was negative in most of the patients (70 %). At the diagnosis, 20 patients (11.3 %) had metastatic disease and 157 were without metastases. Totally 44 patients (32 %) had metastatic disease and most of them (29 patients) had bone disease. Only 52 did not have endocrine therapy with 48 % had tamoxifen as a part of hormonal therapy. Most of them received radiotherapy (54 %). DFS was within 7-182 months with a median of 54 months. PFS was between 2-60 months and patients had a median OS about 61 months. 30 patients died because several causes owing to ageing causes. Conclusions: Breast cancer is the most significant cancer of women and the screening modalities with adjuvant postoperative therapies have increased survival. Acute and chronic medical conditions, nutritional status, poly-pharmacy, level of activity, disease-spesific symptoms and patient decision all need to be taken into consideration. Both in early and advanced stages of the disease, quality of life and related aspects have critical importance in elderly women who have more limited life-expectancy. It is also essential that women with breast cancer 65 years and older be included in trials and that they be recommended the best therapies available.
Regulation of the oxidoreductase ERp57/Grp58 by the stress transcription co-activator LEDGF/p75 in prostate cancer cells
Authors: Melanie Mediavilla-Varela, Tracy Daniels, Carlos Casiano
Journal: Cancer Research (2007)

2914  Prostate cancer (PCa) is the second leading cause of male cancer death in the United States, and is considered a health disparity disease because of its disproportionate incidence and mortality in African American males. A major challenge in PCa treatment is the resistance of advance tumors to therapy due in part to inhibition of apoptotic pathways by survival proteins. The stress response protein Lens Epithelium Derived Growth Factor/p75 (LEDGF/p75) is upregulated by oxidative stress and promotes cell survival by transcriptionally activating stress and anti-oxidant genes. Our group has previously shown that LEDGF/p75 is overexpressed in PCa cell lines and tumors and may act as a pro-survival protein in PCa. Furthermore, we have shown that RWPE-2 PCa cells stably overexpressing LEDGF/p75 significantly increased resistance to cell death induced by docetaxel. To better understand the mechanism by which LEDGF/p75 confers resistance to docetaxel-induced cell death we performed a protein expression profile in PCa cells overexpressing this protein using the Kinetworks Stress/Heat Shock Protein Screen. We observed a marked increase in the expression of ERp57 (endoplasmic reticulum protein 57) in cells stably overexpressing LEDGF/p75. ERp57, also known as glucose regulated protein 58 (Grp58), belongs to the family of thiol oxidoreductase proteins, which have been implicated in protection against cell death through their reactive oxygen species (ROS) scavenging properties. We hypothesized that ERp57 is a target gene of LEDGF/p75 whose upregulation might enhance prostate tumor resistance to docetaxel-induced cell death in PCa. Using luciferase reporter assays we observed transcriptional activation of the ERp57 promoter by LEDGF/p75, which provided evidence that ERp57 might be a target gene of LEDGF/p75. Both proteins were found to be highly expressed in prostate tumor tissues. However, we found little correlation in the protein expression levels of LEDGF/p75 and ERp57 in a panel of PCa cell lines and prostate tumor tissues. This was confirmed by the observation that siRNA-mediated LEDGF/p75 knock-down in PC3 cells did not decrease ERP57 expression. We conclude that while LEDGF/p75 contributes to the upregulation of ERp57, other transcription factors may also regulate ERp57 expression in PCa cells.
Incentivizing Therapies for Rare Diseases—Reply
Authors: Shailin Thomas, Arthur Caplan
Journal: JAMA (2019)

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
An empirical assessment of breast cancer treatment charges by survival status.
Authors: David D. Stenehjem, Arati Dahal, Brandon Kyle Bellows, Diana I. Brixner
Journal: Journal of Clinical Oncology (2013)

e11541 Background: Breast cancer treatment can be costly, but it remains unknown if charges differ between patients who die during treatment compared to survivors. The objective of this study was to assess annualized mean charges by survival status in patients with a diagnosis of breast cancer. Methods: The University of Utah Enterprise Data Warehouse was used to analyze patients ≥18 years with a diagnosis of breast cancer identified by ICD-9 code (initial diagnosis defined as index date) treated at the Huntsman Cancer institute (HCI) from 2002-2010. The HCI Tumor Registry was used to determine stage at diagnosis and other cancers. Cause and date of death was captured from the Utah Population Database. Cancer-related (CR) and non-CR charges were by ICD-9 codes from index date until death or end of the follow-up period, were weighted by the inverse probability of survival, and annualized. Generalized linear models (GLM) with gamma distribution and log link function were used to examine charges by survival status, while adjusting for baseline characteristics including demographics, stage, and comorbidities. Results: There were 1783 patients included, of which 296 (17%) died. Compared to survivors, deceased patients were older (mean age 62 vs. 56), more were diagnosed with stage IV disease (17% vs. 3%), and fewer with stage I (24% vs. 45%); all p&lt;0.001. Mean unadjusted annualized CR charges were not different between groups (deceased $34,310 vs. alive $32,797; p=0.64), but non-CR charges were higher for deceased patients ($39,926 vs. $16,538; p&lt;0.001). GLM results indicated deceased patients had 90% higher annualized CR charges relative to survivors (p&lt;0.001) and higher charges for stages I, II, and III (125%, 86%, and 69%, respectively; all p&lt;0.001). Deceased patients had 124% higher annualized non-CR charges relative to survivors (p&lt;0.001) and higher charges for stages I, II, and III (174%, 146%, and 107%, respectively; all p&lt;0.001). Charges did not differ between groups for stage IV patients. Conclusions: When adjusting for confounders, death was associated with higher CR and non-CR charges, except in patients with stage IV disease at diagnosis. Patients who died during treatment may have had more aggressive disease leading to higher charges.
Quantitative mass spectrometry-based proteomics in the era of model-informed drug development: Applications in translational pharmacology and recommendations for best practice
Authors: Eman El-Khateeb, Areti-Maria Vasilogianni, Sarah Alrubia, Zubida M. Al-Majdoub, Narciso Couto, Martyn Howard, Jill Barber, Amin Rostami-Hodjegan, Brahim Achour
Journal: Pharmacology & Therapeutics (2019)
Retrospective analysis of stage IC uterine cancer patients: A single center experience.
Authors: Nadire Kucukoztas, Selim Yalcin, Samed Rahatli, Ozlem Ozen, Nihan Haberal, Cagla Tarhan, Polat Dursun, Omer Dizdar, Ferah Yildiz, Ozden Altundag, Ali Ayhan
Journal: Journal of Clinical Oncology (2012)

e15573 Background: Stage IC patients are at an increased risk of recurrence and overall worse prognosis compared with stage IA and IB patients. Adjuvant chemoherapy is utilized based on specific pathologic factors. The objective of this study is to evaluate treatment outcomes at a single institution in patients with 1988 FIGO stage IC endometrial adenocarcinoma. Methods: Records of the patients with FIGO stage IB (formerly IC) endometrial cancer were retrospectively evaluated. All patients were initially treated surgically with comprehensive staging lymphadenectomy. Results: A total of 85 patients were included. Patient and tumor characteristics are shown in the table. Median age of the patients was 60 (range 27-95). Fifty-nine patients had at least one co-morbid disease. Complete surgical staging including pelvic and paraaortic lymph node dissection was performed in all the patients. Sixteen patients (19%) received adjuvant chemotherapy, including 6 patients with serous cancer and one patient with small cell cancer. Paclitaxel/carboplatin was the preferred regimen in Median follow up was 30 months (range 10-61 months). Seven patients (8%) relapsed and 4 patients (5%) died on follow up. 5 year disease free survival was 89% and overall survival was 95%. One of the 16 patients (6.2%) who received chemotherapy and 6 of the 69 patients (8.7%) who did not receive relapsed/died on follow up. Survival analysis was not performed because of the low number of events in both groups. Conclusions: We found similar rates of recurrence and death with previous studies in stage IC endometrial cancer. Complete surgical staging is the mainstay of treatment. Marginally lower recurrence rate in chemotherapy treated patients delineate the need for prospective randomized data addressing the role of adjuvant systemic therapy in early-stage patients with endometrial adenocarcinoma. [Table: see text]
FRI0245 The comparison of clinical findings and provocative tests with enmg in carpal tunnel syndrome
Authors: H Ozer, F Sendur, A Aydeniz, G Gurer, E Ozturk
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Carpal tunnel syndrome is most common nerve entrapment syndrome. It occurs by compression of median nerve in carpal tunnel at the wrist. <h3>Objectives</h3> In this study we compared the clinical findings and some provocative tests (Tinnel, Phalen, reverse phalen) with electrophysological examination (ENMG) results. <h3>Methods</h3> This study was carried out on 48 patients who had pain, numbness, tingling and weakness complaints in at least one hand. Provocative tests and ENMG investigation were applied for each patient whom suspected for carpal tunnel syndrome. 67 hands of 48 patients which represent positive sign for carpal tunnel syndrome were evaluated and compared with ENMG positivity. In order to evaluate validity of provacative tests, chi-square test was used. Positive-negative predictive values of provocative tests also investigated. <h3>Results</h3> 20 patients had bilateral complaints, 28 patients had complaints only in one hand. When compared with ENMG results, reverse Phalen test was founded most spesific test (%78.8). This was followed by Tinnel test%72.3 and Phalen test%70.2. <h3>Conclusion</h3> We concluded that provacative tests for ENMG have increased sensitivity, for that reason can be applied in epidemiological studies for carpal tunnel syndrome. But to make an definite diagnosis of carpal tunnel syndrome electrophysiological examination should be applied. <h3>References</h3> Shin JO. Clinical electromyography (Nerve conduction studies), 2nd edn. Baltimore Maryland-USA 21202, 1993 White JC, Hansen SR, Johnson RK. A comparison of EMG procedures in the carpal tunnel syndrome with clinical-EMG correlations. Muscle Nerve 1998;11;1177–82
Assessment of Long-term Distant Recurrence-Free Survival Associated With Tamoxifen Therapy in Postmenopausal Patients With Luminal A or Luminal B Breast Cancer
Authors: Nancy Y. Yu, Adina Iftimi, Christina Yau, Nicholas P. Tobin, Laura van ’t Veer, Katherine A. Hoadley, Christopher C. Benz, Bo Nordenskjöld, Tommy Fornander, Olle Stål, Kamila Czene, Laura J. Esserman, Linda S. Lindström
Journal: JAMA Oncology (2019)

Patients with estrogen receptor (ER)-positive breast cancer have a long-term risk for fatal disease. However, the tumor biological factors that influence the long-term risk and the benefit associated with endocrine therapy are not well understood.To compare the long-term survival from tamoxifen therapy for patients with luminal A or luminal B tumor subtype.Secondary analysis of patients from the Stockholm Tamoxifen (STO-3) trial conducted from 1976 to 1990, which randomized postmenopausal patients with lymph node-negative breast cancer to receive adjuvant tamoxifen or no endocrine therapy. Tumor tissue sections were assessed in 2014 using immunohistochemistry and Agilent microarrays. Only patients with luminal A or B subtype tumors were evaluated. Complete long-term follow-up data up to the end of the STO-3 trial on December 31, 2012, were obtained from the Swedish National registers. Data analysis for the secondary analysis was conducted in 2017 and 2018.Patients were randomized to receive at least 2 years of tamoxifen therapy or no endocrine therapy; patients without recurrence who reconsented were further randomized to 3 additional years of tamoxifen therapy or no endocrine therapy.Distant recurrence-free interval (DRFI) by luminal A and luminal B subtype and trial arm was assessed by Kaplan-Meier analyses and time-dependent flexible parametric models to estimate time-varying hazard ratios (HRs) that were adjusted for patient and tumor characteristics.In the STO-3 treated trial arm, 183 patients had luminal A tumors and 64 patients had luminal B tumors. In the untreated arm, 153 patients had luminal A tumors and 62 had luminal B tumors. Age at diagnosis ranged from 45 to 73 years. A statistically significant difference in DRFI by trial arm was observed (log rank, P < .001 [luminal A subtype, n = 336], P = .04 [luminal B subtype, n = 126]): the 25-year DRFI for luminal A vs luminal B subtypes was 87% (95% CI, 82%-93%) vs 67% (95% CI, 56%-82%) for treated patients, and 70% (95% CI, 62%-79%) vs 54% (95% CI, 42%-70%) for untreated patients, respectively. Patients with luminal A tumors significantly benefited from tamoxifen therapy for 15 years after diagnosis (HR, 0.57; 95% CI, 0.35-0.94), and those with luminal B tumors benefited from tamoxifen therapy for 5 years (HR, 0.38; 95% CI, 0.24-0.59).Patients with luminal A subtype tumors had a long-term risk of distant metastatic disease, which was reduced by tamoxifen treatment, whereas patients with luminal B tumors had an early risk of distant metastatic disease, and tamoxifen benefit attenuated over time.
Whole exome and whole transcriptome sequencing in melanoma patients to identify mechanisms of resistance to combined RAF/MEK inhibition.
Authors: Nikhil Wagle, Eliezer Mendel Van Allen, Dennie T. Frederick, Zachary A. Cooper, Deborah Norman Farlow, Daniel Treacy, Eva M. Goetz, Cory M. Johannessen, Scott L. Carter, Amaro Taylor-Weiner, Eran Hodis, Donald P. Lawrence, Ryan J. Sullivan, Gad Getz, Stacey B. Gabriel, Keith Flaherty, Jennifer Ann Wargo, Levi A. Garraway
Journal: Journal of Clinical Oncology (2013)

9015 Background: The RAF inhibitors vemurafenib and dabrafenib (D) and the MEK inhibitor trametinib (T) improve survival as monotherapies in BRAF-mutant melanoma. Since clinical mechanisms of resistance (MoR) result in MAPK pathway reactivation, recent efforts have focused on combined targeting of RAF and MEK. The combination of D and T (D/T) increased progression-free survival and response rate compared with D alone (Flaherty et al, NEJM, 2012). The MoR to this combination remain unknown. Methods: To look for clinical MoR to combined RAF/MEK inhibition, we performed whole exome (WES) and whole transcriptome sequencing (RNASeq) on tumors from 4 patients (pts) with acquired resistance and 1 pt with intrinsic resistance to D/T. Pre-treatment and post-resistance tumors from all pts were analyzed for point mutations, insertions/deletions, copy number alterations, alternatively spliced transcripts, rearrangements, and expression changes. Results: In 2 of 4 pts with acquired resistance, WES identified mutations in MEK1 and MEK2 that were undetectable in the pre-treatment tumors. In the 3rd pt, RNASeq identified an alternatively spliced isoform of BRAF lacking exons 2-10, also undetectable in the pre-treatment tumor. In the 4th pt, no obvious MoR were seen, though multiple alterations were enriched in the post-resistance tumor. The pt with intrinsic resistance had several alterations in genes that conferred resistance to RAF/MEK inhibition when overexpressed in BRAF-mutant cell lines. Integration of WES and RNASeq data also identified several co-existing alterations that may synergize to increase resistance. Conclusions: Analysis of combined WES and RNASeq data from pt samples provides a more complete picture of clinical MoR to MAPK-targeted therapy. Post-resistance tumors from 3 of 4 pts with acquired resistance to D/T had alterations in MAPK genes not detectable in the pre-treatment tumors, suggesting that resistance involves reactivation of the MAPK pathway despite combined RAF/MEK inhibition. Alternative dosing of current agents, more potent RAF/MEK inhibitors, and/or inhibition of the downstream kinase ERK may be needed for durable control of BRAF-mutant melanoma.
Predictors of survival during treatment of metastatic colorectal cancer with an intermittent chemotherapy regimen.
Authors: Camilla J S Kronborg, Anni Ravnsbæk Jensen
Journal: Journal of Clinical Oncology (2012)

e14063 Background: Patients with metastatic colorectal cancer (mCRC) undergo month to year-long therapy with different chemotherapy regimens and biological agents. We aimed to identify predictors of mortality during an intermittent treatment regimen in an unselected cohort of patients with mCRC. Methods: Consecutive patients, treated from August 2007 until June 2011, were included. Standard 1st line treatment was biweekly FLIRI plus Bevacizumab. Clinical information was obtained from patient files. The outcome was overall survival. Cox regression analysis was used to identify predictors of outcome. We analyzed reduction in chemotherapy dosage (no reduction, ≤75% or &gt;75%), administration of Bevacizumab to ≤50% of chemotherapy treatments, best response during the first 6 months of treatment (NC, RD or PD), and local treatment of metastases (any type). We adjusted for following baseline variables: Gender, age, PS, primary tumor site, resection of primary tumor, metachronous metastases, more than two metastatic sites, liver-only metastases, and low albumin Results: We included 314 patients (median age 64.5 IQ (57-70) years, 194 (61.8%) male). Median follow-up for survival was 471 IQ (257-708) days. One-year survival was 79%, CI (74-84%). Median overall survival was 676 days, CI (577-750). Chemotherapy reduction did not influence outcome, ≤75%: HR 1.08 CI (0.64-1.83), p=0.77, &gt;75%: HR 0.66 CI (0.29-1.5), p=0.32. Local treatment of metastases was borderline significant: HR 0.45 CI (0.20-1.00), p=0.051. Bevacizumab was administered in 262 patients and a reduction in bevacizumab treatments was associated with increased mortality: HR 1.90 CI (1.12-3.23), p=0.018. Regression vs. NC improved outcome HR 0.48 (0.30-0.78), p=0.003, whereas PD vs. NC increased mortality HR 3.84 (1.75-8.42), p=0.001. Conclusions: In an unselected cohort of mCRC patients, using an intermittent treatment regimen, administration of Bevacizumab to less than 50% of chemotherapy treatments and PD were associated with increased mortality. Regression improved outcome compared to stable disease. Local treatment of metastases was borderline significant. Reduction in chemotherapy dosage did not influence outcome.
Links between the gut microbiota, metabolism, and host behavior
Authors: Catherine E. Schretter
Journal: Gut Microbes (2019)

The gut microbiota is known to regulate multiple aspects of host physiology, including metabolism and behavior. Locomotion, which is closely intertwined with metabolism, is an important component of complex behaviors, such as foraging, mating, and evading predators. Our recent work revealed that certain bacterial species and their products modulate motor behavior in the fruit fly Drosophila melanogaster via metabolic and neuronal pathways. In the context of our previously published findings and recent work by others, I will discuss potential avenues for future research at the intersection of the microbiota, metabolism, and host behavior.