tbuckley/cabot-search huggingface dataset:
Effect of celecoxib on neurotoxicity in patients with metastatic colorectal cancer treated with 5-FU/oxaliplatin (CIFOX)
Authors: R. D. Agafitei, S. Schneider, S. Iqbal, D. Yang, S. Groshen, H. J. Lenz
Journal: Journal of Clinical Oncology (2004)

3600 Background: Neuropathy is the dose limiting toxicity for patients with metastatic colorectal cancer treated with 5-FU/oxaliplatin. 5-FU/oxaliplatin was administered on a compassionate use protocol at USC/Norris Cancer Center from November 1998 until May 2001. Methods: The majority of patients (84%) received continuous infusion 5-FU 200 mg/m2/d for 10 weeks with a 2 week break and oxaliplatin 130 mg/m2 every 3 weeks (CIFOX). In October 2000, celecoxib 200 mg bid was added to the regimen, because of the emerging pre-clinical data revealing a potential increase in efficacy and decrease in side effects. We reviewed the reported neurologic toxicities and compared patients who received celecoxib to those who did not. Results: A total of 263 patients were entered onto the trial; 11 were excluded due to lack of toxicity data. 73 patients received celecoxib and 179 did not. Patients on both regimens had similar characteristics. Of the 73 patients who received celecoxib, there were 46(63%) males and 27(37%) females; 12(16%) Asian, 6(8%) African American, 48(66%) Caucasian, and 7(9%) Hispanic; 54(74%) colon cancer and 19(26%) rectal cancer; median age was 61 (range 26–80) years. Of the 179 patients who did not receive celecoxib, there were 120(67%) males and 59(33%) females; 20(11%) Asian, 5(3%) African American, 132(74%) Caucasian, and 22(12%) Hispanic; 153(85%) colon cancer and 26(14%) rectal cancer; median was age 60 (range 24–83). The definition of neuropathy included cold sensitivity, numbness/tingling, paresthesia and jaw discomfort. None of the 73 patients who received celecoxib experienced any grade 3 or 4 neurotoxicity, compared to 10 of the 179 patients who did not receive celecoxib (p=0.024). The patients who received celecoxib were less likely to experience grade 3 or 4 neuropathy, (0% vs. 6%) but more likely to experience grade 1 neuropathy (67% vs. 48%) than those who did not receive celecoxib. Conclusions: These findings are compatible with the hypothesis that celecoxib, when added to 5-FU/oxaliplatin, may reduce the neuropathy associated with this regimen. Prospective clinical trials should be done to confirm these results. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Response Genetics Pfizer; Sanofi
P0331 : The ‘GALAD score’ for serological detection of hepatocellular carcinoma: International validation and assessment of the influence of tumour size and aetiology on model utility
Authors: S. Berhane, H. Toyoda, T. Tada, T. Kumada, C. Kagebayashi, S. Satomura, N. Schweitzer, A. Vogel, M. Manns, J. Benckert, T. Berg, J. Best, A. Dechêne, G. Gerken, J. Schlaak, H.L. Reeves, P. Johnson
Journal: Journal of Hepatology (2015)
The efficacy of varying concentrations of intravesical apaziquone on murine bladder cancer in an animal model.
Authors: B. S. Denes, B. Dénes, C. Nardo, G. Kovács
Journal: Journal of Clinical Oncology (2010)

e15101 Background: This preclinical study compared the efficacy of varying concentrations of apaziquone, an intravesical chemotherapeutic agent currently in clinical trials, and placebo in an animal model of human bladder cancer. The standard dose in all ongoing clinical studies is 4 mg/ 40 mL (0.1mg/mL). Methods: A total of 1x105 MB49 cells were instilled into the bladder of C57BL/6 mice after electrocautery to establish the tumor model. Mice bearing orthotopic tumors received 0.1 mL intravesical instillation of varying concentrations of apaziquone (0.05, n = 10; 0.1, n = 10; 0.4, n = 8, and 0.8 mg/mL, n= 8) or placebo (0.85% saline, n = 8) one week after tumor implantation. Instillations were continued once a week for 4 weeks. Tumor incidence, overall and median survival is reported. Results: At the end of the observation period (80 days), all animals in the control (0.85% saline) and 0.05 mg/mL groups had died. Median survival of mice receiving apaziquone in concentration 0.1 mg/mL (42.5 days); 0.4 mg/mL (40.5 days) and 0.8 mg/mL (49 days) was longer than that of mice treated with 0.05 mg/mL (30 days) and 0.85% saline (27 days). Statistical analyses of survival data was control vs 0.1 mg/mL (P < 0.05); control vs 0.4 mg/mL (P < 0.01), control vs 0.8 mg/mL (P < 0.01); for 0.05 mg/mL vs 0.1 mg/mL (P < 0.05); 0.05 mg/mL vs 0.4 mg/mL (P < 0.01) and 0.05 mg/mL vs 0.8 mg/mL (P < 0.01) respectively. The median survival of the 0.1, 0.4 and 0.8 mg/mL treated groups did not differ, but 33.3% of the 0.1 mg/mL cohort, and 14.3% in the 0.4 mg/mL cohort were long-term survivors (>80 days). All other animals (n = 37) had died of cancer by the end of the observation period. Three mice did not survive anesthesia. At necropsy all mice had advanced local disease with deep invasion of the muscularis propria, and usually with multiple lung metastases. Conclusions: Apaziquone at the 0.1 mg/mL concentration demonstrates excellent antitumor activity compared to placebo or 0.05 mg/mL solutions. In this model there was no significant difference with higher concentrations (0.4 and 0.8 mg/mL) supporting continued development with the current clinical formulation (0.1mg/mL). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Spectrum Pharmaceuticals Spectrum Pharmaceuticals Spectrum Pharmaceuticals Spectrum Pharmaceuticals
Recoding a cocaine-place memory engram to a neutral engram in the hippocampus
Authors: Stéphanie Trouche, Pavel V Perestenko, Gido M van de Ven, Claire T Bratley, Colin G McNamara, Natalia Campo-Urriza, S Lucas Black, Leon G Reijmers, David Dupret
Journal: Nature Neuroscience (2016)
Transarterial injection of Holmium-166-Chitosan complex (Hol-166) in the treatment of single and large hepatocellular carcinoma: A novel therapeutic modality
Authors: J. H. Sohn, J. T. Lee, J. Du Lee, Y. M. Moon, H. C. Chung, J. H. Kim, C. Kim, Y. T. Kim, G. E. Kim, N. C. Yoo
Journal: Journal of Clinical Oncology (2004)

4023 Background; Currently, in terms of treatment modalities of hepatocellular carcinoma (HCC), if surgery is not indicated, transarterial chemoembolization (TACE) is the most widely performed procedure. However, the results of TACE are not so satisfactory. The isotope of Holmium-166 emits 95% of beta ray, which is a high level of energy, and 5% of gamma ray. Using the gamma camera, we can identify the amount and location of the isotope. The effectiveness of Holmium-166 in HCC was first reported in a pre-clinical study (Mumper RJ, 1991). We conducted a prospective trial of intrahepatic artery administration of Hol-166 in a solitary and large (≥ 3cm in diameter) HCC to evaluate response rate and toxicities. This protocol was approved by the institutional review board of the study center and all patients gave written informed consent to participate. Methods: A dose of Hol-166 20 mCi per 1 cm diameter of tumor size was administered through transarterial approach in patients who had following eligibility criteria; 1) No AP shunts 2) No PVT 3) Mass size ≥ 3cm 4) Single lesion 5) No ascites or jaundice Results: A total of 54 patients were enrolled (median follow-up, 38 months). Twenty-seven patients had a tumor size > 5cm, while the other half patients 3–5 cm. The response rate of the total patients was 77% (42/54). Thirty-one patients showed complete necrosis. The incidence of grade 3 or 4 leukopenia was 18.6%, anemia 7.4%, thrombocytopenia 27.8%, AST/ALT elevation 26%/24%, and total bilirubin elevation 5.6%. Treatment related mortalities occurred in two patients. Serious adverse events were reported in 12 cases but recovered with adequate supportive care. In a subset analysis, we have found a substantial difference between two groups (tumor size >5cm vs 3–5cm) in terms of response rate (CR22, PR4 / 27 vs CR 9, PR 7 / 27. p value=0.004) and toxicity. Conclusions: Our results show that this new treatment is highly effective and modestly safe modality in the treatment of HCC. Especially, in patients with tumor size of 3–5cm, a further comparative trial with TACE and even surgery is strongly recommended. No significant financial relationships to disclose.
New group will review evidence for effective care in family planning
Authors: P. O'Brien
Journal: BMJ (1995)

south Wales, and our list size is 5600.All con- sultations in this context were initiated by patients.We routinely code clinical information during consultations on our computer database; this facilitates audit of clinical practice.When a patient is advised about contraception a Read code (6777: contraception counselling) is recorded.Over the 10 weeks before the "pill scare" on 19 October the code for contraception counselling was recorded 18 times (average 1-8 times a week).Over the three weeks after the announcement the code was recorded (week by week) 30, 28, and 27 times (average 28-3).If it is assumed that these figures are reflected throughout England and Wales the effect on general practitioners' workload nationally can be estimated and perhaps costed.
Determinants of Lung Cancer Risk in Cigarette Smokers in New Mexico2
Authors: Dorothy R. Pathak, Jonathan M. Samet, Charles G. Humble, Betty J. Skipper
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Determinants of Lung Cancer Risk in Cigarette Smokers in New Mexico Get access Dorothy R. Pathak, Dorothy R. Pathak Search for other works by this author on: Oxford Academic PubMed Google Scholar Jonathan M. Samet, Jonathan M. Samet Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles G. Humble, Charles G. Humble Search for other works by this author on: Oxford Academic PubMed Google Scholar Betty J. Skipper Betty J. Skipper Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 4, April 1986, Pages 597–604, https://doi.org/10.1093/jnci/76.4.597 Published: 01 April 1986 Article history Received: 01 May 1985 Revision received: 17 October 1985 Accepted: 02 December 1985 Published: 01 April 1986
Government promises £1bn a year more to “transform” mental health in England
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Around £1bn (€1.3bn; $1.5bn) more a year will be spent on improving mental health services in England in the wake of what is being called a landmark report that described a service that still left hundreds of thousands of people with “ruined” lives.

The scale of long term underfunding, neglect, marginalisation, and inadequate service provision was made clear in the NHS commissioned but independent Mental Health Taskforce’s report, published on 15 February.1

The report gathered views from 20 000 members of the public, people with experience of mental health problems, and healthcare professionals.

The government and NHS England have agreed with its recommendations and said that more than £1bn a year of extra funding will be invested in this area of NHS care by 2020-21, to reach one million more people.

In a wide ranging set of recommendations, the report’s authors proposed a …
Behavioral toxicity and equivocal suicide associated with chloroquine and its derivatives
Authors: M I Good, R I Shader
Journal: American Journal of Psychiatry (1977)

Although the antimalarial agents chloroquine, hydroxychloroquine, and amodiaquine are widely used to treat a variety of medical conditions, their behavioral toxicity and lethality are not generally recognized. Therapeutic doses sometimes cause psychosis, delirium, personality change, and depression. Since moderately low overdoses of chloroquine can result in rapid death, such behavioral effects could lead to accidental or state-dependent overdosage and death.
Lung-Resistance–Related Protein Expression Is a Negative Predictive Factor for Response to Conventional Low but not to Intensified Dose Alkylating Chemotherapy in Multiple Myeloma
Authors: H.G.P. Raaijmakers, M.A.I. Izquierdo, H.M. Lokhorst, C. de Leeuw, J.A.M. Belien, A.C. Bloem, A.W. Dekker, R.J. Scheper, P. Sonneveld
Journal: Blood (1998)
Effects of Epidermal Growth Factor on Growth Response, Morphology, and Invasive Potential of Human Endometrial Carcinoma Cell Line RL95-2
Authors: P Sundareshan, R L Misiorowski, J R Davis, M Korc, M J Hendrix
Journal: Cancer Communications (1991)

Exposure of RL95-2 human endometrial adenosquamous carcinoma cells of early passage (less than 30 passages) and late passage (greater than 250 passages) to epidermal growth factor (EGF) resulted in density- and concentration-dependent effects. At low seeding density, EGF (20 nM) inhibited the growth of early passage cells, whereas at high seeding density, 4.98 nM and 20 nM concentrations of EGF stimulated their growth. Furthermore, the growth of late passage cells was stimulated by 0.0166 nM EGF and inhibited by 4.98 nM and 20 nM EGF at both seeding densities. EGF (20 nM) caused marked morphological changes of both passages at the low seeding density. Inhibition of invasion of both passages through Matrigel-coated filters was seen at low seeding density, while at the high seeding density, EGF enhanced invasiveness. At high seeding density, EGF stimulated an increase in urokinase type plasminogen activator activity, which may have augmented the ability of cells to degrade the extracellular matrix. In addition, the ability of high seeding density cells of both passages to adhere to matrigel after EGF treatment correlated with invasiveness.
Feasibility of cetuximab in combination with gemcitabine or docetaxel or carboplatin/gemcitabine for chemonaïve patients with advanced non-small cell lung cancer (NSCLC): Observations from an ongoing randomized phase II/III trial (GemTax IV)
Authors: L. R. Pilz, S. Cicenas, C. Eschbach, J. R. Fischer, C. Kortsik, C. Schumann, M. Serke, M. Steins, C. Manegold
Journal: Journal of Clinical Oncology (2008)

19005 Background: The novel therapeutic agent cetuximab, a monoclonal antibody that specifically targets the epidermal growth factor receptor, is currently registered for colorectal and head and neck cancer and is undergoing broad clinical investigations in advanced NSCLC. This randomized trial assesses the feasibility of cetuximab in combination with two common chemotherapeutic regimens in patients with locally advanced or metastatic NSCLC. Early phase II results are reported. Methods: Patients with histologically confirmed stage IIIB or IV NSCLC, WHO performance status 0–2, and no prior chemotherapy received cetuximab 400 mg/m2 as initial dose then 250 mg/m2 weekly either in combination with gemcitabine 1,000 mg/m2 days 1 and 8 for two 3-weekly cycles followed by docetaxel 75 mg/m2 day 1 for 2 cycles (q3w) or gemcitabine 1200 mg/m2 days 1 and 8 and carboplatin AUC5 day 1 for a maximum of 4 cycles (q3w). Cetuximab was administered until disease progression or unacceptable toxicity. Results: 142 patients evaluable for toxicity received 404 cycles of cetuximab (1119 infusions) in combination with chemotherapy and 285 cycles (797 infusions) of single-agent cetuximab (maintenance phase). Toxicity results are given (table). Conclusions: Cetuximab does not add significantly to known chemotherapy toxicity in the induction phase and is well tolerated in the maintenance phase. Toxicity Results Cetuximab plus Gemcitabine Cetuximab plus Docetaxel Cetuximab plus Gemcitabine/Carboplatin Cetuximab Maintenance No. of cycles (No. of patients) 125 (72) 68 (40) 211 (70) 285 (53) Median No. of cycles 2 2 4 4 Grade 3/4 anemia + ≥ 1 blood transfusion during treatment cycle (% cycles) - - 3 - Grade 3/4 thrombocytopenia + ≥ 1 platelet transfusion during treatment cycle (% cycles) - - 5 - Grade 3/4 febrile neutropenia + IV antibiotics during treatment cycle (% cycles) - 2 - - Grade 3/4 skin reaction (% cycles) 6 7 5 1 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly, Merck Pharma Eli Lilly, Merck Pharma Eli Lilly, Merck Pharma, sanofi-aventis
Phase I/II trial of chemoradiotherapy concurrent with S-1 and cisplatin in patients with clinical stage II/III esophageal carcinoma: Results of the Japan Clinical Oncology Group study JCOG 0604.
Authors: Makoto Tahara, Nozomu Fuse, Junki Mizusawa, Akihiro Sato, Keiji Nihei, Keisuke Kanato, Ken Kato, Kentaro Yamazaki, Kei Muro, Hiromasa Takaishi, Narikazu Boku, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2014)

134 Background: We conducted a phase I/II trial of chemoradiotherapy (CRT) concurrent with S-1 and cisplatin to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and safety in patients with esophageal carcinoma. Methods: Eligibility criteria included histologically proven squamous cell or adeno carcinoma of the thoracic esophagus, clinical stage II/III excluded T4, PS 0-1, age 20 to 75, and no prior treatment. Chemotherapy consisted of administration of S-1 60-80 mg/m 2 /day on days 1-14, and cisplatin at 75 mg/m 2 on day 1, repeated twice every 4 weeks. Single daily radiation of 1.8 Gy in 28 fractions (total 50.4Gy) was given concurrently starting on day 1. For patients achieving an objective response after CRT, two additional cycles of chemotherapy were administered. The phase I part adopted the 3+3 cohort design. Planned sample size of 75 patients was calculated based on the weighting of threshold values of CR rate according to the registered proportion of T1-2 and T3. Results: Patient accrual was terminated early due to slow enrollment after 44 eligible patients were accrued from May 2007 to Sep 2011. Patient backgrounds were: 40 males, with median age 62 years, PS 0/1 (39/5), squamous cell carcinoma / adenocarcinoma (43/1), T1/T2/T3 (14/8/22) and N0/N1 (7/36). In the phase I part, two of six patients experienced DLTs at each level of S-1 (S-1 60 or 80 mg/m2/day). Considering treatment compliance, RD was determined as S-1 60 mg/m2/day. The CR rate, primary endpoint of phase II, was 59.5% (22/37; 90%CI, 44.6-73.1%; the weighted threshold, 57.2%; p=0.46) on central review. In the phase II part, 3-year progression-free survival was 47.3% and 3-year overall survival was 61.9%. Grade 3 or 4 toxicity in phase II part included leukopenia (57.9%) neutropenia (50%), hyponatremia (28.9%), anorexia (21.1%), anemia (18.4%), thrombocytopenia (18.4%), and febrile neutropenia (2.6%). No treatment-related deaths were observed. Conclusions: Although CRT with S-1 plus cisplatin showed acceptable toxicity and favorable 3-year survival, this study did not meet its primary endpoint. Clinical trial information: 000000710.
Emergency care specialists renew call for out-of-hours services to be located in hospitals
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

Out-of-hours urgent and emergency primary care services should be located in hospital emergency departments with immediate effect, specialists have said.

In a joint position statement the Royal College of Emergency Medicine and Urgent Health UK, the federation of social enterprise providers of unscheduled primary care, said that the move would secure safer, simpler, and more effective access for patients with urgent healthcare needs outside normal GP clinic hours.

Chris Moulton, vice president of the Royal College of Emergency Medicine, said, “Recent research by the Royal College of Emergency Medicine has confirmed that around …
A Communication Approach for Oncologists: Understanding Patient Coping and Communicating About Bad News, Palliative Care, and Hospice
Authors: Juliet Jacobsen, Vicki A. Jackson
Journal: Journal of the National Comprehensive Cancer Network (2009)

Oncologists frequently approach patients to discuss difficult topics, such as bad news about cancer progression and referrals to palliative care and hospice. To communicate effectively in these difficult situations, it is helpful to assess what the patient knows and wants to know about their disease in general and, specifically, their prognosis. Although some patients fully accept the diagnosis of cancer and cope well, most patients struggle with how best to cope. This struggle often manifests itself with the patient vacillating between unrealistic hopes for longevity while also indicating prognostic awareness by talking about funeral plans. Although this coping is normal, it is difficult for most clinicians to interpret. This article presents a framework for understanding normal patient coping and gives specific examples of how to talk with these patients during difficult transitions, such as times of disease progression, and about referral to hospice and palliative care.
A Three-Dimensional Organoid Culture System Derived from Human Glioblastomas Recapitulates the Hypoxic Gradients and Cancer Stem Cell Heterogeneity of Tumors Found <i>In Vivo</i>
Authors: Christopher G. Hubert, Maricruz Rivera, Lisa C. Spangler, Qiulian Wu, Stephen C. Mack, Briana C. Prager, Marta Couce, Roger E. McLendon, Andrew E. Sloan, Jeremy N. Rich
Journal: Cancer Research (2016)

Many cancers feature cellular hierarchies that are driven by tumor-initiating cancer stem cells (CSC) and rely on complex interactions with the tumor microenvironment. Standard cell culture conditions fail to recapitulate the original tumor architecture or microenvironmental gradients and are not designed to retain the cellular heterogeneity of parental tumors. Here, we describe a three-dimensional culture system that supports the long-term growth and expansion of tumor organoids derived directly from glioblastoma specimens, including patient-derived primary cultures, xenografts, genetically engineered glioma models, or patient samples. Organoids derived from multiple regions of patient tumors retain selective tumorigenic potential. Furthermore, organoids could be established directly from brain metastases not typically amenable to in vitro culture. Once formed, tumor organoids grew for months and displayed regional heterogeneity with a rapidly dividing outer region of SOX2(+), OLIG2(+), and TLX(+) cells surrounding a hypoxic core of primarily non-stem senescent cells and diffuse, quiescent CSCs. Notably, non-stem cells within organoids were sensitive to radiotherapy, whereas adjacent CSCs were radioresistant. Orthotopic transplantation of patient-derived organoids resulted in tumors displaying histologic features, including single-cell invasiveness, that were more representative of the parental tumor compared with those formed from patient-derived sphere cultures. In conclusion, we present a new ex vivo model in which phenotypically diverse stem and non-stem glioblastoma cell populations can be simultaneously cultured to explore new facets of microenvironmental influences and CSC biology. Cancer Res; 76(8); 2465-77. ©2016 AACR.