tbuckley/cabot-search huggingface dataset:
Association between KIR genes and risk of MDS.
Authors: May Daher, Catherine Sobieski, David Marin, Takuya Sekine, Elizabeth J. Shpall, Richard E. Champlin, Hagop M. Kantarjian, Guillermo Garcia-Manero, Katayoun Rezvani
Journal: Journal of Clinical Oncology (2015)

7001 Background: Myelodysplastic syndrome (MDS) represents a spectrum of clonal hematopoietic disorders affecting the myeloid lineage, characterized by cytopenias and dysplastic features. MDS is risk-stratified according to International Prognostic Scoring System (IPSS) scores. The major clinical complication in these disorders, especially in the high-risk group, is the potential to evolve into acute myeloid leukemia (AML). Evidence is accumulating that genetic factors play an important role in conferring susceptibility/resistance to MDS. In this regard, activating killer-cell immunoglobulin-like receptor (KIR) genes expressed in natural killer cells (NK cells) are of particular interest. Humans may inherit different numbers of the six distinct activating KIR genes. Little is known about the impact of this genetic variation on the innate susceptibility or resistance of humans to develop MDS. Methods: We addressed this issue by performing a case-control study involving 180 MDS patients (120 with high IPSS, 60 with low IPSS) and 117 healthy donors. DNA samples were collected in both cases and controls and analysis of activating KIR genes was performed using PCR. Results: Our results showed that patients with high-risk MDS had significantly lower numbers of activating KIR genes compared to patients with low-risk MDS (P = 0.009) and compared to healthy controls (P = 0.00001). Patients with low-risk MDS also had fewer activating KIR genes when compared to controls (P = 0.04). Importantly, inheritance of each additional activating KIR gene had a protective effect against development of high risk MDS (RR 0.7, P < 0.001). Conclusions: These results suggest that inheritance of a higher number of activating KIR genes is protective against MDS, and that once the disease develops, harboring a lower number of KIR genes is associated with higher risk disease. Hence, our study provides novel insights concerning the pathogenesis of MDS in adults and has implications for the development of new immunotherapies using NK cells with potential of controlling the disease and preventing progression to high risk disease and eventually to AML.
Une médecine generale en crise peut-elle assumer une formation à la relation thérapeutique?
Authors: O. Rosowsky
Journal: Psychotherapy and Psychosomatics (1972)

Beside individuel resistance which prevent the extension of training in the therapeutical relationship, there are cultural and socio-economical factors of a new type, working at the level of the patients, the social partner and the doctors. As a result the relational 'demand' undergoes an increase among the patients, whereas the 'supply' decreases among the practioners. What we have instead is a caricature of availability, granted by family-doctors who are obliged to do so because of very strong social, economical and juridical pressures. As things are, his life experience of constraint as well as the exhausting rhythm of his work, make the family-doctor, insofar as professional group, little inclined to seize the training in psychotherapy offered to him.
Thoracic radiation therapy added to chemotherapy for small-cell lung cancer: an update of Cancer and Leukemia Group B Study 8083.
Authors: M C Perry, J E Herndon, W L Eaton, M R Green
Journal: Journal of Clinical Oncology (1998)

PURPOSE To provide a 10-year update of the experience of the Cancer and Leukemia Group B (CALGB) in the addition of thoracic radiation therapy to chemotherapy in limited-stage small-cell lung cancer. PATIENTS AND METHODS Three hundred ninety-nine patients with limited-stage small-cell lung cancer were randomized to receive thoracic radiation therapy that started on day 1 (arm I) or day 64 of chemotherapy treatment (arm II), or chemotherapy alone with cyclophosphamide, vincristine, and etoposide (later, doxorubicin). Thoracic radiation therapy consisted of 4,000 rad to the tumor and mediastinum with a 1,000-rad boost. All patients received prophylactic cranial radiation to a dose of 3,000 rad. RESULTS Arm I patients had a median survival of 13.04 months, arm II patients 14.54 months, and arm III patients 13.58 months (log-rank test, P = .0072). Median time to clinical failure was 11 months in arm I, 11.21 months in arm II, and 8.7 months in arm III (log-rank test, P = .0004). CONCLUSION With 10 years of follow-up, the two arms that included thoracic radiation therapy remain superior to chemotherapy alone. The addition of thoracic radiation therapy to combination chemotherapy improved both complete response rates and survival, with increased but acceptable toxicity.
Delayed toxicity of whole brain radiotherapy (WBRT) in germ cell tumor (GCT) patients with central nervous system (CNS) metastases
Authors: D. M. Doyle, L. H. Einhorn
Journal: Journal of Clinical Oncology (2007)

15511 Background: CNS metastases are uncommon in GCT. Incidence is 2–3% and is usually associated with extensive pulmonary metastases and/or high serum human chorionic gonadotropin levels. CNS metastases have been managed with WBRT and concomitant cisplatin-based combination chemotherapy. Our prior publication did not observe serious CNS toxicity (Int J Rad Oncol Biol Phys 22:17–22, 1991). Methods: We observed 5 patients with delayed CNS toxicity. Initial diagnosis was 1981 through 2003. Median age 23 years (range 21–34). All 5 patients had advanced disease by the International Germ Cell Consensus Collaborative Group. Three of five patients had CNS metastases at the time of diagnosis, and two patients relapsed with CNS metastases. These 5 patients received WBRT 4,000–5,000 cGy in 18- 28 fractions concurrently with cisplatin-based chemotherapy. Results: All five patients developed delayed symptoms consistent with progressive multifocal leukoencephalopathy (PMLE), including seizures, hemiparesis, expressive and receptive aphasia, cranial neuropathies including facial droop, tremors, headaches, blindness, dementia, decreased level of consciousness, ataxia, and parasthesias. Median time from WBRT to CNS symptoms was 72 months (range 9–228 months). Brain imaging revealed multiple abnormalities consistent with gliosis and diffuse cerebral atrophy. One patient was diagnosed with glioblastoma multiforme in the area of radiation-induced gliosis. 3 of 5 patients had progressive symptoms, and the other 2 had stable symptoms. Treatment with surgery and steroids had modest benefit. The PMLE resulted in significant debility in all five patients, resulting in death (2 patients), loss of work, steroid-induced morbidity, and recurrent hospitalizations. Conclusions: WBRT is not innocuous in young patients with GCT and can cause late CNS toxicity. We are now cautious about the use of WBRT and reserve it for multiple CNS metastases that are symptomatic or resistant to chemotherapy. No significant financial relationships to disclose.
An extreme codon preference strategy: codon reassignment.
Authors: G E Andersson, C G Kurland
Journal: Molecular Biology and Evolution (1991)

We argue that in animal mitochondria codon reassignments, such as those for AGA and AGG from arginine to serine or of AUA from isoleucine to methionine, are the result of an interplay between biased mutational forces and selective ones. In particular, there is a marked tendency for animal mitochondria to have very small genomes and to minimize their investment in components required for gene expression. These tendencies are expressed as a reduction in the diversity of tRNA isoacceptor species. In our view, the pressure to simplify tRNA populations, together with mutational bias against certain codons, will account for the codon reassignments observed in animal mitochondria. A parallel to the major codon bias in microorganisms, which likewise tends to reduce the diversity of the tRNA isoacceptor populations under fast growth conditions, may be drawn. Therefore, we suggest that codon reassignments are usefully viewed as an extreme form of codon bias.
How reliable is a negative MRI/TRUS fusion biopsy? The predictive value of targeted biopsy for prostate cancer.
Authors: Michele Fascelli, Rachael Sussman, Thomas P Frye, Arvin Koruthu George, Steven Abboud, Raju Chelluri, Richard Ho, Anna Mary Brown, Sandeep Sankineni, Maria J Merino, Baris Turkbey, Peter L. Choyke, Bradford J. Wood, Peter A. Pinto
Journal: Journal of Clinical Oncology (2015)

51 Background: Multiparametric MRI (mpMRI) has been shown to improve clinically significant prostate cancer (CaP) detection. Targeted biopsy using MRI/transrectal ultrasonography (TRUS) fusion is a novel diagnostic tool. The negative predictive value (NPV) of an MRI/TRUS fusion targeted biopsy of a suspicious lesion on mpMRI was determined. Methods: 30 of 181 men who underwent prostatectomy from 2008-2014 were retrospectively identified and had at least one lesion on mpMRI negative for cancer on MRI/TRUS fusion biopsy. Whole mount pathology specimens, gold standard for CaP detection, were aligned with MRI to assess true histopathology of all identified targets. Lesions negative for CaP on biopsy and not identified as cancer on pathology were considered true negatives (TN). Lesions biopsied negative but later found to possess foci of CaP on whole mount were considered false negatives (FN). Calculations of NPV were then made per biopsy year, MRI suspicion score, and lesion size on MRI. Results: 48 lesions of a total 81 identified on mpMRI were reported negative for CaP in the 30 patients who underwent fusion biopsy. Of these, 37 lesions were found to be truly negative on histopathology, while 11 lesions had CaP foci on whole mount specimen. Overall NPV was 77% (37/48). The NPV increased over time (Table 1), and was as high as 85.7% most recently. Conclusions: This series demonstrated a NPV of 77% for targeted MRI/TRUS fusion biopsy of lesions seen on mpMRI. The increasing NPV trend noted over time may have further applications to assess the learning curve for this diagnostic method. Not surprisingly, NPV is higher for low and moderately suspicious lesions than for highly suspicious lesions. This data may help physicians interpret the clinical implications of a negative fusion biopsy. [Table: see text]
The role of heredity in cancer.
Authors: E G Levine, R A King, C D Bloomfield
Journal: Journal of Clinical Oncology (1989)

Heredity is generally felt to play a minor role in the development of cancer. This review critically examines this assumption. Topics discussed include evidence for heritable predisposition in animals and humans; the potential importance of genetic-environmental interactions; approaches that are being used to successfully locate genes responsible for heritable predisposition; comparability of genetic findings among heritable and corresponding sporadic malignancies; and future research directions. Breast, colon, and lung cancer are used to exemplify clinical and research activity in familial cancer; clinical phenotypes, segregation and linkage analyses, models for environmental interactions with inherited traits, and molecular mechanisms of tumor development are discussed. We conclude that the contribution of heredity to the cancer burden is greater than generally accepted, and that study of heritable predisposition will continue to reveal carcinogenic mechanisms important to the development of all cancers.
Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin's disease.
Authors: M H Leibenhaut, R T Hoppe, B Efron, J Halpern, T Nelsen, S A Rosenberg
Journal: Journal of Clinical Oncology (1989)

Between July 1968 and July 1986, 915 patients with clinical stage (CS) I and II Hodgkin's disease limited to sites above the diaphragm underwent laparotomy and splenectomy at Stanford University. Fifteen percent were CS I, of whom 76% had cervical/supraclavicular disease, 13% axillary disease, and 9% mediastinal presentations. CS I patients were more likely to be male, were significantly older, and were significantly less likely to have nodular sclerosis (NS) histology than CS II patients. Twenty percent of CS I patients and 30% of CS II patients were pathologically upstaged. No CS I patients were upstaged to pathological stage (PS) IV. Univariate and multivariate analyses of presenting clinical characteristics were performed to predict staging laparotomy findings. CS I women, CS I patients with mediastinal-only disease, and CS I men with either lymphocyte predominance or interfollicular histologies were at low risk for having disease below the diaphragm (5%) or requiring chemotherapy (0%). CS II women who were less than 27 years old and had only two or three sites of disease were also at low risk for upstaging (9%) or requiring chemotherapy (2%). Mixed cellularity histology and male gender were associated with increased risk for subdiaphragmatic disease and require laparotomy; the presence of systemic symptoms was not correlated with laparotomy findings. These results confirm the importance of performing staging laparotomy for the majority of patients who present with supradiaphragmatic Hodgkin's disease if treatment programs are based on the presence and extent of subdiaphragmatic disease. Selected subgroups are at low risk for subdiaphragmatic disease and might be spared laparotomy if they are treated with mantle, paraaortic, and splenic irradiation.
Oncologists’ Role in Patient Fertility Care
Authors: Teresa K. Woodruff, Kristin Smith, William Gradishar
Journal: JAMA Oncology (2016)

Oncofertility is a term coined just a few years ago to address the urgent, unmet needs of young cancer patients who were offered life-preserving but fertilitythreatening treatments. The issue for many oncologists was not that they did not want to provide options to their patients; rather, the option list and the physician groups on the fertility side were limited. This issue has largely been addressed and the remaining barriers are few. Here are answers to the questions most frequently asked of oncologists by patients. 1. Dopatientscareaboutfertilityinthefaceofacancer diagnosis? Yes, many studies conducted over the past 5 years have shown that young women and men are concerned about their endocrine health and the fertility consequences of cancer treatment. Patients who are not told about later fertility concerns at the time of diagnosis have stress levels in the range of posttraumatic stress disorder during survivorship. 1,2 Thus, oncologists are urged to provideafertilityconsultationtomitigatethelong-termhealth consequence associated with treatment. 2. What amount of time is necessary for women to leave oncology care, be assessed by a reproductive endocrinologist, decide what method to use for fertility preservation, go through the fertility care cycle, and return to oncology care? Five years ago, ovarian stimulation cycles could take up to 6 weeks to time the start of the cycle. This is no longer standard of care. “Random start” fertility cycles induce ovarian follicle development at anytime during the cycle and take about 2 weeks from the start of ovarian stimulation medications to oocyte retrieval. 3 This minimizes the time between diagnosis and cancer treatment. Moreover, egg cryopreservation is now standard of care, eliminating difficult decisions regarding use of a partner’s or donor’s sperm and long-term storage of embryos. 4
HER2 guided neoadjuvant treatment of advanced breast cancer: Clinico-biological correlations
Authors: D. Crivellari, G. Miolo, D. Lombardi, S. Massarut, T. Perin, S. Venturini, V. Di Lauro, R. Dolcetti, S. Tumolo, A. Veronesi
Journal: Journal of Clinical Oncology (2008)

11559 Background: Tailoring neoadjuvant chemotherapy (NACT) ± trastuzumab (T) according to tumor/host features remains an open issue, with special reference to anthracycline omission in HER2+ cases. Methods: Patients (pts) with breast cancer (BC), NACT candidate, were eligible. HER2+ pts (n=12) received 24 wks of weekly T 4mg/kg loading dose d1 then 2mg/kg and Paclitaxel (P) 80 mg/m2 before surgery, followed by additional 12 wks of TP and T for 1 year. HER2- pts (n=21) received 8 cycles of epirubicin (E) and docetaxel (D) (90 and 75mg/m2 respectively, q3 wks) before surgery, followed by 3 CMF cycles. Hormone therapy was suggested in all hormone sensitive cases. The primary endpoint was pCR and its correlation with Topo2α expression and the extent of spontaneous T cell responses to HER2 and other BC-associated antigens. Results: The TP regimen gave a clinical response in all 8 evaluable pts (clinical complete remission (CR) in 3 pts, partial remission (PR) in 5). Radical mastectomy (RM and quadrantectomy (Q) were performed in 6 and 2 pts, respectively. Pathologic (p) response rate was 87% with 3 pCR. Nodal pCR occurred in 5/7 pts. The ED regimen gave a 79% clinical response rate in the 14 evaluable pts (CR in 7, PR in 4). RM and Q were performed in 8 and 6 pts, respectively. P response rate was 78.6% with 2 pCR. Nodal pCR occurred in 3/12 pts. Toxicity: onychopathy G3, alopecia G2, paresthesia G2 and mucositis G3 more frequent in the TP pts, neutropenia G3–4, febrile neutropenia, anemia G3 and alopecia G2 more frequent in ED. No cardiotoxicity was observed. Conclusions: This interim analysis suggests that the TP as NACT in HER2+ BC has a good efficacy and tolerability. Clinico-biological correlations are underway. No significant financial relationships to disclose.
Potentiation of cisplatin ototoxicity by noise.
Authors: M A Gratton, B A Kamen
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.12.2091 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2230903 Potentiation of cisplatin ototoxicity by noise. M A GrattonxM A GrattonSearch for articles by this author , B A KamenxB A KamenSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.12.2091 PDF "Potentiation of cisplatin ototoxicity by noise.." Journal of Clinical Oncology, 8(12), pp. 2091–2092© 1990 by American Society of Clinical Oncology
Relapse patterns and outcomes in a population-based study of Nova Scotia patients with germ cell tumors (GCT)
Authors: E. Murphy, J. Douglas, Q. Qi, L. Wood
Journal: Journal of Clinical Oncology (2007)

15564 Objectives: To examine the frequency and pattern of relapse in a population-based cohort of Nova Scotia patients with germ cell tumors (GCT). Presentation and outcome of these patients will be described with an emphasis on late relapsers. Methods: A retrospective chart review of all patients diagnosed with GCT in Nova Scotia between 1984 and 2004 was completed. Data regarding initial diagnosis and treatment as well as data at time of relapse was collected. Relapse was defined as any recurrence of tumor after initial definitive therapy. Late relapse (LR) was defined as a relapse &gt;2 years from initial definitive therapy or previous relapse. Results: Of the 383 patients diagnosed with GCT during the 20 year period, 135 received chemotherapy. 15/135 (3.7%) patients initially treated with chemotherapy relapsed; 10 early and 5 late. 1/10 early relapsers was alive and NED at 2 years from relapse compared to 4/ 5 late relapsers at 4 years. 3 of the 245 patients whose treatment did not include chemotherapy experienced a LR for a total of 8/383 (2.1%) of all patients. Median time to all LR was 6.6 years. Pathology for 6/8 (75%) patients with LR was nonseminomatous GCT. 50% of patients with LR died. Common to all LR survivors was complete surgical resection ± chemotherapy. All patients with LR who died had either no surgical resection or incomplete surgical resection of disease. Conclusions: The incidence of all GCT patients with LR was 2.1% and the incidence of LR post chemotherapy was 3.7% in this population. The only other population based report of incidence of LR in all GCT patients was 1.3%. A mixture of stages, pathology, and sites of metastases was observed with no obvious baseline or treatment differences between early and late relapsers. Interestingly, in this population, patients with LR had better outcomes than early relapsers. The success to curing patients with LR appears to be complete surgical resection of disease. No significant financial relationships to disclose.
5-Fluorouracil, hydroxyurea and escalating doses of iododeoxyuridine with concomitant radiotherapy for malignant gliomas: A clinical and pharmacologic analysis
Authors: E E Vokes, M E Dolan, S Krishnasamy, R Mick, M J Ratain, F Berezin, D Brachman, G Whitman, R L Schilsky, J Charette
Journal: Annals of Oncology (1993)

Iododeoxyuridine (IUdR) is a known radiation enhancer, and interacts biochemically with 5-fluorouracil (5-FU) and hydroxyurea (HU).IUdR was added to the previously studied regimen of continuous infusion 5-FU at 300 mg/m2/day for 5 days, HU 500 mg every 12 hours for 11 doses and radiotherapy 200 cGy/day for 5 days, all administered for 7 consecutive weeks to patients with malignant glioma. IUdR was administered as 5-day continuous intravenous infusion during weeks 1 and 4. The IUdR dose was changed in cohorts of patients. IUdR plasma concentrations were determined during weeks 1 and 4, and IUdR incorporation into the DNA of granulocytes was measured on weeks 2 and 5.Two patients treated at the initial IUdR dose of 500 mg/m2/day developed grade 3 or 4 myelosuppression and mucositis. Additional dose levels of IUdR tested were 250 mg/m2/day and 125 mg/m2/day; at the latter dose, severe or life-threatening toxicity was seen in only 3 of 8 patients treated. IUdR incorporation into DNA of granulocytes was 10.5(+/- 2.3)% at an IUdR dose of 500 mg/m2/day but decreased to 0.76(+/- 0.3)% at 125 mg/m2/day. Similarly, IUdR plasma concentrations decreased from 436 (+/- 114) ng/ml to 99 (+/- 29) ng/ml.The addition of IUdR to 5-FU and HU results in significant systemic toxicity necessitating limitation of the IUdR dose to 125 mg/m2/day. There is a significant biochemical interaction between IUdR, 5-FU and HU leading to increased IUdR incorporation into DNA and to substantial clinical toxicity. Further clinical studies to exploit this interaction at more feasible schedules may be useful.
异丙酚安全性 异丙酚安全、广泛地用于急诊科
Authors: Aruni, Sen, 王征
Journal: BMJ (2010)

Hattie和Malhotra报告了异丙酚在当前麻醉用药中的益处，并透露了它的低滥用倾向。。然而他们错误地认为，异丙酚只能由“特定的人”即麻醉师及监护医师使用才安全。他们忽略了急诊医师同样成功安全地将其广泛用于操作时镇静”。该药作用时间短，遵循4小时准则，即便在监管人中也很常用。
Rituximab and risk of second primary malignancies in patients with non-Hodgkin lymphoma: a systematic review and meta-analysis
Authors: I. Fleury, S. Chevret, M. Pfreundschuh, G. Salles, B. Coiffier, M.H.J. van Oers, C. Gisselbrecht, E. Zucca, M. Herold, M. Ghielmini, C. Thieblemont
Journal: Annals of Oncology (2015)
Alternating combination chemotherapy for stages III and IV ovarian carcinoma.
Authors: J A Young, A Johnson, J Kroener, J A Koziol, S Saltzstein, J L Yon, T N Campbell, W Lucas, M R Green
Journal: Journal of Clinical Oncology (1984)

Thirty-nine previously untreated patients with stages III and IV ovarian carcinoma were treated with debulking surgery, followed by alternating combination chemotherapy with cisplatin, Adriamycin (Adria Laboratories, Columbus, Ohio), and cyclophosphamide (PAC); and hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil (HexaCAF). Of 19 patients with measureable disease at the onset of therapy, ten (53%) had at least a partial response to chemotherapy. Seven (18% of total) patients were found to be pathologically free of disease at secondlook surgery, but four patients relapsed 19 to 31 months after initiating therapy. The median progression-free survival period of all 39 patients entered into the study is 12 months, and the median crude survival is 21 months. The PAC/HexaCAF alternating combination chemotherapy regimen may be administered with moderate toxicity, but the treatment results are not superior to those reported for PAC or HexaCAF alone in advanced ovarian carcinoma.