tbuckley/cabot-search huggingface dataset:
Expression of the Nonmuscle Myosin Heavy Chain IIA in the Human Kidney and Screening for MYH9 Mutations in Epstein and Fechtner Syndromes
Authors: Christelle Arrondel, Nicolas Vodovar, Bertrand Knebelmann, Jean-Pierre Gru[Combining Diaeresis]nfeld, Marie-Claire Gubler, Corinne Antignac, Laurence Heidet
Journal: Journal of the American Society of Nephrology (2002)

Mutations in the MYH9 gene, which encodes the nonmuscle myosin heavy chain IIA, have been recently reported in three syndromes that share the association of macrothrombocytopenia (MTCP) and leukocyte inclusions: the May-Hegglin anomaly and Sebastian and Fechtner syndromes. Epstein syndrome, which associates inherited sensorineural deafness, glomerular nephritis, and MTCP without leukocyte inclusions, was shown to be genetically linked to the same locus at 22q12.3 to 13. The expression of MYH9 in the fetal and mature human kidney was studied, and the 40 coding exons of the gene were screened by single-strand conformation polymorphism in 12 families presenting with the association of MTCP and nephropathy. MYH9 is expressed in both fetal and mature kidney. During renal development, it is expressed in the late S-shaped body, mostly in its lower part, in the endothelial and the epithelial cell layers. Later, as well as in mature renal tissue, MYH9 is widely expressed in the kidney, mainly in the glomerulus and peritubular vessels. Within the glomerulus, MYH9 mRNA and protein are mostly expressed in the epithelial visceral cells. Four missense heterozygous mutations that are thought to be pathogenic were found in five families, including two families with Epstein syndrome. Three mutations were located in the coiled-coil rod domain of the protein, and one was in the motor domain. Two mutations (E1841K and D1424N) have been reported elsewhere in families with May-Hegglin anomaly. The two others (R1165L and S96L) are new mutations, although one of them affects a codon (R1165), found elsewhere to be mutated in Sebastian syndrome.
Differing Perspectives on Breast Cancer Chemoprevention
Authors: V. Craig Jordan
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Enhancement of radiation-induced downstaging of rectal cancer by fluorouracil and high-dose leucovorin chemotherapy.
Authors: B D Minsky, A M Cohen, N Kemeny, W E Enker, D P Kelsen, B Reichman, L Saltz, E R Sigurdson, J Frankel
Journal: Journal of Clinical Oncology (1992)

PURPOSE To determine if fluorouracil (5-FU) plus high-dose leucovorin (LV) enhances local response in patients receiving preoperative radiation therapy (RT) for adenocarcinoma of the rectum, we compared the degree of downstaging in patients receiving preoperative RT with or without chemotherapy. PATIENTS AND METHODS For this comparison, three groups of patients who were treated with identical doses and techniques of preoperative pelvic RT (total dose of 5,040 cGy) were examined. Group 1 included 20 patients with unresectable disease who received combined RT and LV/5-FU. Group 2 included 11 patients with unresectable disease who received preoperative RT. Group 3 included 21 patients with invasive, resectable, primary disease who received preoperative RT. RESULTS Patients with unresectable disease who received LV/5-FU had a higher rate of pathologic complete response (20% v 0%) and a lower incidence of positive nodes (30% v 64%) compared with those who did not receive chemotherapy. Even when the most favorable group of patients was included (group 3), patients who received LV/5-FU still had a higher complete response rate (20% v 6%) and a lower incidence of positive nodes (30% v 53%) compared with those who received RT without LV/5-FU. Of those patients with initially unresectable disease, the resectability rate was higher in those who received LV/5-FU compared with those who did not receive LV/5-FU (90% v 64%). Patients who received LV/5-FU experienced slightly more grade 1 to 2 fatigue, stomatitis, nausea, and grade 3 diarrhea, tenesmus, and dysuria. CONCLUSIONS Despite the fact that patients who received chemotherapy (group 1) had more advanced disease compared with those with resectable disease (group 3), the addition of LV/5-FU increased the resectability and downstaging rates. The ultimate impact of a complete response as well as a decrease in the incidence of pelvic nodes on local control and survival remains to be determined. However, given the enhancement of down-staging in patients with unresectable rectal cancer, we are encouraged by the combined modality approach.
Ifosfamide plus oral etoposide salvage chemotherapy for platinum-resistant paclitaxel-pretreated ovarian cancer
Authors: G. Aravantinos, M.A. Dimopoulos, P. Kosmidis, D. Bafaloukos, C. Papadimitriou, C. Kiamouris, N. Pavlidis, K. Sikiotis, P. Papakostas, D.V. Skarlos
Journal: Annals of Oncology (2000)
Use of the FDA spontaneous adverse event reporting system (SAERS), or why your MedWatch reports really do matter
Authors: S. D. Ross, M. W. Reynolds
Journal: Journal of Clinical Oncology (2004)

6089 Background: The purpose of this project is to demonstrate how a publicly available data source is used for safety assessments in cancer drug development and commercialization. Methods: Oxaliplatin was approved in August 2002 for second-line use in metastatic colorectal cancer. Peripheral sensory neuropathy commonly occurs with oxaliplatin, and at least 4 cases of autonomic neuropathy (with Lhermitte's sign and urinary retention), have also been reported. We searched the FDA SAERS database, which is comprised predominantly of MedWatch reports filed by physicians, for reports suggesting either of these frequent or infrequent types of neuropathy. Proportional reporting ratios (PRR) were calculated for oxaliplatin relative to other platinum compounds. PRRs > 3.0 are suggestive of a “signal”, but need a larger context to interpret. Results: Relevant PRRs as of March 21, 2003 are shown for MedDRA High Level Terms (HLT) and various Preferred Terms (PT) subsumed under the HLTs. The PRR for oxaliplatin is statistically significant and lower than for other platinum compounds for “peripheral neuropathy”, but higher for “sensory abnormalities”. Reports of urinary symptoms are few, but appear to be comparable (at the HLT) for all platinum drugs. Conclusions:Oncologists can actively contribute to the drug safety monitoring of all patients by submitting MedWatch reports to the FDA SAERS. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MetaWorks, Inc. MetaWorks, Inc. MetaWorks, Inc.
Effect of rifampin (RIF) on the pharmacokinetics (PK) of atrasentan (ABT-627, ATN)
Authors: H. Xiong, J. Jankowski, E. Ashbrenner, Y. L. Chiu, M. Mendoza, P. Wang, N. McCracken, R. A. Carr, T. Doan, A. Allen
Journal: Journal of Clinical Oncology (2004)

4728 Background: ATN, an oral endothelin antagonist with high selectivity for ETA receptor, is currently in phase 3 clinical development for the treatment of hormone-refractory prostate cancer. In humans, oral ATN is extensively metabolized, equally distributed between oxidation and glucuronidation. In vitro, CYP3A was the predominant isozyme involved in oxidative metabolism. The antibiotic RIF is a potent inducer of metabolic enzymes, including CYP3A, and is recommended by FDA as a probe of choice to determine the maximal inducing effect on a CYP3A-metabolized drug. RIF is also known to inhibit the liver basolateral uptake transporters OATP-C and OATP8. Methods: To assess the effect of RIF on ATN PK, a phase 1 open label study was conducted in 12 healthy male subjects (mean±SD 36±11 yrs, 78±10 kg). Subjects received ATN 10 mg PO on Days 1 and 12. RIF 600 mg PO QD was given from Day 4 through 14. Blood samples for ATN assay were collected predose and over 72 h after each ATN dose. Plasma concentrations of ATN were determined using a validated LC/MS/MS method. Results: ATN PK are summarized (mean±SD; N=12) in the following table. ATN with RIF was generally well tolerated; all AEs were mild. Conclusions: Effects on ATN PK by RIF co-administration were consistent with a biphasic interaction hypothesis. In the early phase (first several h), RIF competitively inhibited ATN uptake by the liver. In the later phase, when RIF plasma concentrations were low, the interaction was dominated by CYP3A induction. RIF co-administration is expected to have similar effects on steady-state ATN PK, and is therefore expected to be well-tolerated and have little if any effect on atrasentan efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories
PWE-234 Management and outcomes of intestinal failure in a district general hospital setting: Abstract PWE-234 Table 1
Authors: C Tamura, R Kalaiselvan, A Kenyon, D Smith, N Sarwar, CJ Walsh
Journal: Gut (2015)

<h3>Introduction</h3> Centralisation of intestinal failure (IF) services is being considered. It will not be possible to manage all patients with type 2 IF in national centres and many patients will need to be managed regionally. We have audited our practice of type 2 and 3 IF with respect to aetiology, management and outcomes in a DGH setting. <h3>Method</h3> Retrospective analysis of consecutive patients admitted with type 2/3 IF requiring parenteral nutrition (PN) for &gt; 28 days between 01/09/2009–31/07/2014 was done from prospectively maintained database and cross-referenced with case notes (electronic and paper). Data are represented as median (range). <h3>Results</h3> There were 84 patients (45 women) admitted during the study period. The median age was 68 (20–90) years. <h3>Aetiology</h3> <h3>PN details</h3> Patients were managed on PN for a median of 65 (29–728) days while being an in-patient. The catheter related infection rate was 0.16 CRBI /1000 catheter-days. PN was administered by peripherally inserted central catheters by a nurse led service. <h3>Outcome</h3> Nutritional autonomy was achieved following conservative management in 17 (20%) patients. 46 (55%) underwent one-stage (n = 24) or two-stage (n = 22) surgical procedures and achieved nutritional autonomy. 8(10%) required home parenteral nutrition of which 6 were palliative patients who were discharged to hospice and 2 were referred to national IF centres. 12(14%) with type 2 IF and 1 (1%) with type 3 IF died in hospital. At a median follow-up of 479 (19–1885) days, 18 (21%) with type 2 IF and 6 (7%) with type 3 IF died. <h3>Conclusion</h3> Sepsis management and safe PN administration is the key to managing patients with IF and can be done in regional units. <h3>Disclosure of interest</h3> None Declared.
A study of in-patient oncology satisfaction.
Authors: Nagabhishek Moka, Steven Jubelirer, Christine A. Welch, Martha B. Taylor
Journal: Journal of Clinical Oncology (2014)

205 Background: The European Organization for Research and Treatment in Cancer (EORTC) developed the EORTC-IN-PATSAT32 survey for in-patient satisfaction (use permission granted). Methods: The EORTC-IN-PATSAT32 survey administered after consent, at discharge on an oncology floor at a large university affiliated community hospital. Comparisons were made to Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS), which were collected during the same time period. Results: The average age of those completing the 282 surveys was 60.2 ± 12.3. Males made up 50.2% of the population, 96% were Caucasian, 66% were married, and 49% had a high school education or less, 4% were enrolled in a clinical trial and 75% had researched illness on the internet. Physicians and nurses were ranked highest for there technical skill 90 ±16 and 87±17, respectively and lowest for their availability, 85±2 and 81±24, respectively. The services and care organization was ranked highest for other hospital staff interpersonal skills, 80±20 and lowest for hospital access, 70±25. Even though 87% of the population ranked there overall stay as very good or excellent there were differences seen between groups. Males were more satisfied with the information they received about care (p = 0.04), and their overall hospital stay (p = 0.03) than females. Patients treated by a medical oncologist were more satisfied with the information the received (p = 0.03) compared to other specialties. Married patients found access to facilities was better (p = 0.03) than unmarried patients. Those ≥ 65 were more satisfied with the exams, interest, and comfort of the nursing staff (p =.03) than their younger counterparts. HCAHPS (always rank) was higher than EORTC (excellent rank) for information (p &lt;.0001), personnel listening ( p &lt; 0.0001), and hospital cleanliness (p = 0.008), however no difference was seen in overall rating of care (p = 0.45). Conclusions: The majority of patients were satisfied with their care. Patients gender, marital status, age and the specialty of the physician were significant factors in determining satisfaction. Survey administration differences may contribute to difference between EORTC and HCAHPS. Hospital staff need to be cognizant of possible unintended bias towards various groups of patients.
A phase II study of oral MKC-1 for metastatic breast cancer (MBC)
Authors: B. P. Schneider, M. Karwal, L. Laufman, L. Sylvester, M. A. Taylor, C. Sidor, A. Hannah, J. Arnott, K. D. Miller
Journal: Journal of Clinical Oncology (2008)

1046 Background: MKC-1 is a novel oral cell cycle inhibitor with in vitro and in vivo activity against many tumor cell lines, including breast cancer. Proteins identified as binding targets of MKC-1 include microtubules and members of the importin-β family. Additionally, MKC-1 has been demonstrated to inhibit the Akt-mTOR signaling pathway in vitro and in vivo. This phase II study evaluated the efficacy and safety of MKC-1. Methods: Eligible patients (pts) had MBC previously treated with an anthracycline (A) and a taxane (T). Pts with treated/stable CNS metastases were eligible. Pts were treated with MKC-1 at 125 mg/m2 BID D1–14 of every 28 day cycle. Dose escalation/reductions were made based on first cycle neutropenia. The primary endpoint was objective response rate (ORR) by RECIST. Enrollment was to continue to 53 evaluable pts if ≥2 of the first 23 responded. Results: A total of 58 pts have now been enrolled. Median age/ECOG performance status was 60/0. Receptor status: 53% ER/PR+ and 17% Her2+. Median number of cycles was 2 (range 1 - 8). Grade ≥3 drug-related toxicity (n=42) was as follows: elevated AST/ALT (7%), sensory neuropathy (2%), elevated creatinine (2%), mucositis (2%), and neutropenia (7%), including one death from neutropenic sepsis. 5 pts discontinued due to toxicity. Of pts proceeding to cycle 2, 51% and 11% had the dose increased or reduced, respectively. 49 patients were evaluable for response. ORR was 3/49 (6.1%) and an additional 7 pts had stable disease. 1 pt (adjuvant AC/paclitaxel and docetaxel/cisplatin for metastatic disease) had a PR (observed after cycle 4; confirmed after cycle 6; withdrawal for progression at cycle 8). The 2nd pt (adjuvant CMF with A/docetaxel, capecitabine and nab- paclitaxel for metastatic disease) had an unconfirmed CR after 3 cycles. Confirmatory scans were not possible because pt chose to withdraw from study. The 3rd pt (AC/docetaxel for metastatic disease) had a PR and remained on-study for 5 cycles. Conclusions: MKC-1 is well tolerated at its recommended dose and schedule. Activity is observed in pts previously receiving A/T for MBC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration EntreMed EntreMed EntreMed EntreMed
Improvement in the survival for adult soft tissue sarcoma with adjuvant anthracycline chemotherapy combination: A meta-analysis and metaregression.
Authors: S. L. Afonso, L. A. Ramos, G. A. Viani, E. Stefano, V. Afonso
Journal: Journal of Clinical Oncology (2010)

10042 Background: A growing body of literature suggests that adjuvant anthracycline chemotherapy combination may have potential to improve survival in patients with soft tissue sarcoma. Our aim was to examine the strength of this association through a detailed meta-analysis and metaregression analysis of randomized controlled trials (RCTs). Methods: Eligible trials were identified first from earlier published meta-analyses and systematic reviews. We also used MEDLINE, Cancerlit, and EMBASE databases to identify additional studies and published abstracts from major scientific meetings since 1980. Only RCTs with an analysis by an intention-to-treat principle were included. Pooled relative risk (RR) estimates and 95% confidential intervals (CIs) were calculated using the random- and fixed-effects models. Subgroup and meta-regression analyses were also conducted. Results: Eighteen RCTs of adjuvant anthracycline chemotherapy combination for soft tissue sarcoma contributed to the analysis (n=2145). Adjuvant anthracycline chemotherapy use was associated with a substantially increased for overall survival (RR=0.88, 95% CI 0.80-0.97, p=0.015), disease-free survival (p<0.0001), local recurrence (p=0.009) and metastases-free survival (p<0.001). In the subgroup analysis, anthracycline plus ifosfamide was the only chemotherapy combination associated with increased of the survival. The metaregression analysis did not indicate that anthracycline total dose or anthracycline dose per cycle used in the studies was associated to death risk. Conclusions: Our data suggests that there is a survival benefit for adjuvant anthracycline based chemotherapy in STS. The anthracycline/ifosfamide regimen was the only subgroup of the chemotherapy combinations for which this benefit was seen. Our data could not identify a relationship between risk of death and anthracycline total dose or dose per cycle. No significant financial relationships to disclose.
Diffuse large B-cell lymphoma (DLBCL) of the waldeyer'ring (WR) frequently have a GC-like phenotype: a clinico-pathological study of 209 patients from the groupe d'étude des lymphomes de l'adulte (GELA).
Authors: Laurence de Leval, Christophe Bonnet, J. Brière, T. Molina, T. Petrella, J. Bosq, B. Falini, C. Gisselbrecht, F. Reyes, Georges Fillet, P. Gaulard
Journal: Annals of Oncology (2008)
Autologous bone marrow transplant in acute myeloid leukemia in first remission.
Authors: P A Cassileth, J Andersen, H M Lazarus, O M Colvin, J M Bennett, E A Stadtmauer, H Kaizer, R S Weiner, M Edelstein, M M Oken
Journal: Journal of Clinical Oncology (1993)

PURPOSE The Eastern Cooperative Oncology Group conducted a prospective study of postremission high-dose chemotherapy and autologous bone marrow transplantation (autoBMT) in a group of uniformly treated adults with de novo acute myeloid leukemia (AML) to evaluate whether intensive, myeloablative therapy in first complete remission (CR) could improve the disease-free survival. PATIENTS AND METHODS After initial CR was induced by the combination of daunorubicin, cytarabine, and thioguanine, patients not eligible for allogeneic bone marrow transplantation (alloBMT) were offered autoBMT. Within a median of 2 months after CR, and without intervening postremission therapy, bone marrow was obtained, purged by exposure to 4-hydroperoxycyclophosphamide (4-HC), and cryopreserved. High-dose therapy consisted of oral busulfan over 4 days (16 mg/kg total) followed by intravenous (IV) cyclophosphamide 50 mg/kg daily for 4 days. The cryopreserved marrow was then reinfused. RESULTS Of the 39 patients scheduled for autoBMT, four relapsed before transplantation. Two of the 35 (6%) transplant patients died of transplant-related complications, and 11 (33%) relapsed a median of 8 months after marrow reinfusion. No relapse has occurred after 24 months posttransplant. With a median follow-up of 31 months, the median disease-free survival period for all 39 patients has not been reached; however, 54% +/- 16% of patients are projected to be alive and disease-free at 3 years. CONCLUSION Long-term, disease-free survival after autoBMT in AML seems to be better than the outcome after conventional-dose postremission therapy and rivals the results of alloBMT.
Combined-modality treatment of small-cell lung cancer: Randomized comparison of three induction chemotherapies followed by maintenance chemotherapy with or without radiotherapy to the chest
Authors: R.A. Joss, P. Alberto, E.A. Bleher, C. Ludwig, P. Siegenthaler, G. Martinelli, C. Sauter, E. Schatzmann, H.J. Senn
Journal: Annals of Oncology (1994)
대한간학회 제 8 차 춘계학술대회 초록집 / 포스터 발표 : 만성 B 형 간염에서 간섬유화의 지표로서 AST / ALT 와 혈소판 수치의 임상적 유용성
Authors: 박수영, 이종협, 정민규, 김은수, 조창민, 탁원영, 권영오, 김성국, 최용환
Journal: Clinical and Molecular Hepatology (2002)
Immunocytochemical assay for estrogen receptor in patients with breast cancer: relationship to a biochemical assay and to outcome of therapy.
Authors: R A McClelland, U Berger, L S Miller, T J Powles, R C Coombes
Journal: Journal of Clinical Oncology (1986)

We developed an immunoperoxidase technique using a monoclonal antibody to the estradiol receptor (ER) to identify immunoreactive ER (iER) in breast carcinomas and compared this with the conventional dextran-coated charcoal (DCC) steroid binding assay. We also examined the relationship between the iER and response to therapy in patients with advanced breast cancer. We found iER-positive cells in 60 of 90 carcinomas (66.7%); this correlated with the DCC assay (r = 0.76; P less than .001). Of these, 56 patients were found to be assessable for response to endocrine therapy. Twenty-two showed an objective response to some form of endocrine manipulation, and all these had positively stained carcinomas. By deriving a staining intensity index (SII) we observed that 21 of 22 responders (95%) had an SII of greater than or equal to 0.5, whereas only 8 of 34 nonresponders (24%) had an SII of greater than or equal to 0.5. This difference is highly significant (P less than .001). None of the 17 patients with negatively stained carcinomas responded to endocrine therapy. We conclude that the monoclonal antibody to ER can help identify breast cancer patients who may respond to endocrine therapy.