tbuckley/cabot-search huggingface dataset:
Computational modeling of the effect of the mismatch repair protein hMLH1 upon cell cycle responses and cytotoxicity of 5-iododeoxyuridine (IUdR) in colon cancer cells.
Authors: Jane Schupp, Evren Gurkan-Cavusoglu, Mohammad Aziz, Yuji Seo, Kenneth Loparo, Timothy Kinsella
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4411 

Previous studies in our laboratory have described increased and preferential radiosensitization of mismatch repair (MMR) deficient colon cancer cells with 5-iododeoxyuridine (IUdR). We have shown that mismatch repair deficient colon cancer cells incorporate 25% to 42% more IUdR than mismatch repair competent cells, and that IUdR and IR interact to produce up to three-fold greater radiosensitivity in MMR deficient cells. The present study utilizes mathematical models to describe the effects of IUdR incorporation upon the cell cycle for the purpose of increasing IUdR radiosensitivity in mismatch repair deficient cells by improving the timing of the ionizing radiation (IR) to maximize the DNA damage caused by IR-induced base excision repair responses. To date, two computational models have been developed towards this goal, the first being a stochastic model of the progression of cell cycle states, which gives the cell cycle distribution at any given time for two synchronized colon cancer cell lines, one proficient for mismatch repair and the other deficient, treated with and without IUdR. The second model defines the relation between the percentage of cells in the different cell cycle states at any time, and the corresponding IUdR incorporation at this point. Together, these models can be combined to predict IUdR incorporation at any time in the cell cycle by substituting the distributions of the first model into the second model. Ultimately these mathematical models can be used to maximize therapeutic gain in mismatch repair deficient cells by predicting the optimal dose and the optimal time in the cell cycle for delivery of IUdR and IR to increase the synergistic action of the DNA repair responses to IUdR- and IR- induced damage. Further computational modeling studies are being developed to this purpose.
P66 SVR with telaprevir, peginterferon alfa-2A and ribavirin in HCV patients with well-characterised prior null response, partial response, viral breakthrough or relapse after peginterferon+ ribavirin
Authors: G Dusheiko, T Berg, J M Pawlotsky, P Ferenci, S Zeuzem, A J Muir, F Poordad, M L Shiffman, J Heathcote, H Reesink, N Adda, J G McHutchison
Journal: Gut (2010)

Introduction  Study107 is an open-label rollover study of telaprevir (T) with peginterferon+ ribavirin (PR) in genotype-1 HCV patients who did not achieve SVR following PR treatment in telaprevir Phase 2 studies.  Method  Null responders ( 10  HCV RNA decrease at week-4 or  10  at week-12), partial responders (=2-log 10  decrease at week 12, detectable at week 24), patients with viral breakthrough and relapsers from PROVE1/2/3 PR arms were eligible for treatment. Initially all patients received T 750 mg q8h plus PR at standard doses for 12 weeks, followed by 12 weeks of PR (T12/PR24). Protocol was amended to allow partial responders, viral breakthroughs and relapsers with undetectable HCV RNA at weeks 4 and 12 (eRVR) to receive T12/PR24. Partial responders, viral breakthroughs and relapsers with detectable HCV RNA at week 4 and/or week 12 and null responders received an additional 24 weeks of PR (T12/PR48).  Results  Of 117 patients included in an ITT analysis, 97 (83%) had baseline HCV RNA=800 000 IU/ml, (69) 59% had genotype subtype 1a, 44 (38%) had cirrhosis or bridging fibrosis, and 9 (8%) were black. Viral breakthrough and relapse rates occurred in 25%, 23% of prior null responders; 10%, 22% of prior partial responders; 13%, 0% of prior viral breakthroughs; and 0%, 4% of prior relapsers.  Conclusion  Patients with prior relapse, breakthrough and partial response exhibited high SVR rates after 24 weeks of telaprevir-based regimen. High SVR rates were also observed in patients with previous null response after 48 weeks of therapy.
Micrornas Expression in Blood Associated with Taxanes Response and Overall Survival in Metastatic Castration-Resistant Prostate Cancer
Authors: M. Marín-Aguilera, O. Reig, G. Carrera, L. Gaba Garcia, N. Jiménez, V. Pereira, P. Gascon, B. Mellado
Journal: Annals of Oncology (2014)
Antifactor VIII Antibody Inhibiting Allogeneic but not Autologous Factor VIII in Patients With Mild Hemophilia A
Authors: Kathelijne Peerlinck, Marc G. Jacquemin, Jef Arnout, Marc F. Hoylaerts, Jean Guy G. Gilles, Renaud Lavend’homme, Karen M. Johnson, Kathleen Freson, Dorothea Scandella, Jean-Marie R. Saint-Remy, Jos Vermylen
Journal: Blood (1999)
OC-067 A single-blinded study evaluating the effects of a gluten-free diet in diarrhoea-predominant irritable bowel syndrome
Authors: I Aziz, J North, N Trott, R Briggs, DS Sanders
Journal: Gut (2015)

<h3>Introduction</h3> Gluten has been shown to alter bowel barrier function in patients with diarrhoea-predominant irritable bowel syndrome (D-IBS), particularly those who are HLA-DQ positive. <h3>Aims</h3> To assess the clinical response to a gluten-free diet (GFD) in D-IBS patients previously naïve to the effects of gluten and blinded to HLA-DQ status. <h3>Method</h3> Between May 2012 to December 2014 we enrolled 48 D-IBS patients (24 HLA-DQ positive and 24 HLA-DQ negative) to undertake a six-week GFD. Patients commenced a GFD after seeing an expert dietitian. Both patients and dietitian were blinded to HLA-DQ status. Questionnaires were self-completed at baseline and at week 6. The primary end-point was change in IBS-symptom severity score (IBS-SSS), with a 50 point reduction conferring clinical benefit. Secondary end-points were change in IBS-quality of life (IBS-QOL), short form-36 (SF-36), hospital anxiety and depression score (HADS) and fatigue impact score (FIS). <h3>Results</h3> Data from 41 patients (74.4% women, mean-age 40.3 yrs) was available for per protocol analysis. Of these, 21 were HLA-DQ positive and 20 HLA-DQ negative; baseline characteristics were similar other than worse physical-fatigue (0.04) and vitality (0.05) in the HLA-DQ positive group. Overall, a GFD reduced IBS-SSS ≥50 points in 76% (n = 31). In fact, the mean-total IBS-SSS decreased from 286 to 131 (change –155, p &lt; 0.001); this was seen similarly across both HLA-DQ groups. There was also a significant improvement in IBS-QOL, SF-36, HADS, and FIS amongst both groups. However, HLA-DQ positive subjects showed a greater response to depression (p = 0.02), fatigue (physical, p = 0.04; cognitive, p = 0.07) and vitality (p = 0.05) compared to HLA-DQ negative subjects. On study completion, 90% (n = 37) were discharged and 61% (n = 25) continued with a GFD. <h3>Conclusion</h3> A GFD is a therapeutic option for the management of D-IBS. A clinical improvement was seen in 76% of patients undertaking a six-week GFD, with 61% opting to continue with a GFD for the foreseeable future. The pathophysiological mechanism may differ according to HLA-DQ status. <h3>Disclosure of interest</h3> None Declared.
Relationship of programmed death 1 (PD-1) expression to the recurrence in gastric cancer.
Authors: Shohei Eto, Takashi Iwata, Kozo Yoshikawa, Jun Higashijima, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Mitsuo Shimada
Journal: Journal of Clinical Oncology (2015)

31 Background: PD-1 (Programmed Death 1), a member of the B7-CD28 family, is a cell surface coinhibitory receptor expressed on T cells, B cells, monocytes, and natural killer T cells, following activation. Recently, PD-1 expression is involved with malignancy have been reported in cancer cells and virus-infected cells. The aim of this study is to clarify the impact of PD-1 expression on long term outcome of gastric cancer. Methods: Total of 105 patients who were performed gastrectomy in Stage 2/3 gastric cancer. For resected specimen was performed immunostaining of PD-1. We counted PD-1 positive T cells in the tumor across five adjoining high power fields (×400 magnification level). And, we calculated the percentage of the total cell number, it was considered PD-1 positive more than 40%. We investigated clinicopathological factors and survival. Results: 28 cases were PD-1 positive expression. There was no significant difference between the two groups in the clinicopathological factors (age, gender, tumor size, differentiation, depth of invasion, lymph node metastasis, stage, lymphatic invasion and venous invasion). There was no difference in overall survival rate at 3 years (PD-1 positive vs. negative 76% vs. 81%, p=0.552). PD-1 positive expression was significantly poorer in disease-free survival rate (36% vs. 65%, p=0.022). 10 cases were Foxp3 positive expression, and Foxp3 positive expression was related with PD-1 expression. Conclusions: The PD-1 expression in the tumor could be a potential prognostic factor in gastric cancer.
Observations on Radiation-Induced Lymphoid Tumors of Mice
Authors: Rakesh Kumar
Journal: Cancer Research (2016)

See related article by Kaplan, [Cancer Research 1947;7:141–7][1] .

Visit the Cancer Research 75th Anniversary [timeline][2].

Here we highlight Dr. Henry S. Kaplan's article, “Observations On Radiation-Induced Lymphoid Tumors Of Mice,” published in the March 1947 issue of Cancer Research ([1
Treatment of the patient with stage M0 soft tissue sarcoma.
Authors: H D Suit, H J Mankin, W C Wood, M C Gebhardt, D C Harmon, A Rosenberg, J E Tepper, D Rosenthal
Journal: Journal of Clinical Oncology (1988)

During the period 1971 to 1985, 220 patients with soft tissue sarcoma of the extremities, torso, and head-neck region were managed by radiation and resectional surgery at the Massachusetts General Hospital (MGH). Actuarial 5-year local control and disease-free survival rates were 86% and 70%, respectively. The success rate improved during this time period. Namely, the local control rates for 1971 to 1975, 1976 to 1980, and 1981 to 1985 were 81%, 81%, and 94%, respectively. For the same time periods, the 5-year disease-free survival rates were 64%, 70%, and 76%. One hundred thirty-one patients were treated with postoperative radiation, and 89 with preoperative radiation. In the most recent 5-year period, the local control rates were 91% and 97% for the two groups (number of patients being 50 and 57 in the post- and preoperative groups, respectively). Treatment by preoperative radiation appears to have a major advantage for patients with very large sarcomas, ie, greater than 15 cm in maximum dimension. None of our patients with local control of grade 1 sarcoma have developed distant metastasis (DM). In contrast, among patients with grade 2 or 3 sarcomas, there is a relentless and progressive increase in the frequency of DM with size of the primary lesion, namely, 6% at less than or equal to 2.5 cm, congruent to 60% at 15 to 20 cm, and congruent to 80% at greater than 20 cm.
Ifosfamide - etoposide chemotherapy in patients with advanced adult soft tissue sarcomas
Authors: A. Kawai, H. Chuman, A. Makimoto, Y. Ito, U. Yamaguchi, Y. Morimoto, Y. Beppu
Journal: Journal of Clinical Oncology (2004)

9062 Background: Doxorubicin and ifosfamide are considered to be the two most active agents in the treatment of adult soft tissue sarcoma (STS). Etoposide has substantial activity in wide range of malignancies and is highly active against sarcomas in children and young adults when combined with ifosfamide. There are several conflicting data about the effect of ifosfamide - etoposide combination chemotherapy in adult patients with STS. The objective of current study was to determine the efficacy of this combination in advanced adult STS. Methods: Patients who had histologically confirmed advanced non-small round cell STS were enrolled. At least 4 weeks interval was present since previous chemotherapy. Patients received 5-day cycles of ifosfamide (1.8g/m2/day) and etoposide (100mg/m2/day). Etoposide was administered over 2 hours and followed immediately by ifosfamide infused over 2 hours. Mesna uroprotection (60% dose of ifosfamide) was given. The response was evaluated after at least two chemotherapy courses. Results: Twenty-two patients (15–69 years, median 41) with advanced adult STS were enrolled onto this study. Histological diagnoses comprised 6 synovial sarcoma, 5 MFH, 5 MPNST, 2 liposarcoma, 2 leiomyosarcoma, and 2 others. Primary sites were extremity in 14 and trunk in 8. Evaluation sites were metastatic disease in 13, local recurrence in 5 and inoperable primary tumor in 4. Six patients achieved partial response, 14 had stable disease and 2 had progressive disease, with an overall response rate of 27%. Of 8 patients who had received previous anthracycline containing chemotherapy, two responded. Two of five patients with MPNST and MFH had objective tumor regression. Treatment was well tolerated except for neutropenic fever that occurred in 10% of the courses. Conclusions: Etoposide has minimal activity in advanced adult STS when combined with ifosfamide using this administration regimen. Considering the schedule dependency of etoposide, the contribution of prolonged infusion of etoposide combining with ifosfamide should be further investigated. No significant financial relationships to disclose.
A Transplantable Rat Hepatocellular Carcinoma Induced by Ethionine
Authors: Sidransky, Herschel
Journal: JNCI Journal of the National Cancer Institute (1962)

Journal Article A Transplantable Rat Hepatocellular Carcinoma Induced by Ethionine Get access Herschel Sidransky Herschel Sidransky Laboratory of Pathology, National Cancer Institute,4Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 28, Issue 6, June 1962, Pages 1425–1435, https://doi.org/10.1093/jnci/28.6.1425 Published: 01 June 1962 Article history Received: 17 January 1962 Published: 01 June 1962
Concomitant radical non-platinum radiochemotherapy for elderly patients with invasive bladder cancer
Authors: A. Rodica Maricela, L. N. Minea, X. Bacinschi, I. Isacu, A. Tarlea
Journal: Journal of Clinical Oncology (2009)

e16135 Background: Treatment of bladder cancer in elderly patients is a challenging problem because surgery is often not tolerable and the combination of extensive radiotherapy with chemotherapy is also difficult because of patients’ compliance and associated comorbidities. Our study evaluated concurrent radiochemotherapy in elderly patients with locally advanced bladder cancer (T2-T4) in terms of efficacy and tolerability. Methods: Between January 2005 and December 2007, we treated 34 patients with transitional carcinoma of the bladder, with or without nodal involvement, no distant metastases, and median age 79 years (range 66 - 89 years). Their performance status was 0–1-2 in 10–16–8 patients respectively. Cardiovascular comorbidities were the most common (15 patients). The treatment consisted in conformal radiotherapy (mean irradiation dose = 56.4 Gy) concomitant with biweekly Gemcitabine 200 mg/sqm starting on day 1 of radiotherapy. Results: Response was assessed at 4–6 weeks after the end of treatment by cystoscopy with biopsies and MRI. All the patients could end the intended radiation therapy but four of them could not tolerate all the chemotherapy. 13 patients achieved complete response, 12 patients - partial response and 9 patients stable disease. The most common toxicities were: diarrhea (grade 1–2 in 11 patients, grade 3–6 patients), cystitis (grade 1–2 in 5 patients), leucopenia (grade 1–2 in 12 patients, grade 3–4 in 2 patients), thrombocytopenia (grade 1–2 in 6 patients) and anemia (grade 1–2 in 4 patients). Three patient required hospitalization for dehydration and two for febrile neutropenia. After a median follow-up time of 17.4 months, there were 7 relapses and 5 distant metastases. One-year survival rate was 82.41% (28 patients). 6 patients died, 3 from their cancer and 3 from comorbidities. Conclusions: Chemoradiation is well enough tolerated even in elderly patients and also an efficient and organ sparing therapeutic alternative for patients over 65 years old. The treatment choice was based on patients’ preference considering better quality of life with bladder preservation. The use of age-specific therapy adjustments has shown that aggressive treatment for bladder cancer is associated with improved survival even in elderly patients. No significant financial relationships to disclose.
British Association of Dermatologists and British Photodermatology Group guidelines for the safe and effective use of psoralen–ultraviolet A therapy 2015
Authors: T.C. Ling, T.H. Clayton, J. Crawley, L.S. Exton, V. Goulden, S. Ibbotson, K. McKenna, M.F. Mohd Mustapa, L.E. Rhodes, R. Sarkany, R.S. Dawe, P.M. McHenry, J.R. Hughes, M. Griffiths, A.J. McDonagh, D.A. Buckley, I. Nasr, V.J. Swale, C.E. Duarte Williamson, N.J. Levell, T. Leslie, E. Mallon, S. Wakelin, P. Hunasehally, M.J. Cork, S. Ungureanu, J. Donnelly, K. Towers, C. Saunders, R. Davis, A.G. Brain, L.S. Exton, M.F. Mohd Mustapa
Journal: British Journal of Dermatology (2016)

These guidelines were first produced by the British Photodermatology Group in 1994 (oral PUVA) and in 2000 (topical PUVA) This update was produced jointly by the British Photodermatology Group and the British Association of Dermatologists Conflicts of interest: THC (1) advisory board payment -Johnson & Johnson (non-specific); ( 2) conference organising fee -Galderma (non-specific); SI (1) travel expenses and honoraria -Galderma, Spirit and Ambicare Health (non-specific); (2) research support -Ambicare Health (nonspecific)
Rapid Development of Bronchiolo-Alveolar Squamous Cell Tumors in Rats After Intratracheal Injection of 3-Methylcholanthrene&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Hans Schreiber, P. Nettesheim, D. H. Martin
Journal: JNCI Journal of the National Cancer Institute (1972)

Bronchiolo-alveolar squamous cell tumors were induced in the lungs of specific-pathogen-free Fischer 344 rats by intratracheal injections of 3-methylcholanthrene (MCA). The tumors appeared as early as 2 weeks after the last of 5 weekly injections of 5 mg MCA, or 5 weeks after a single injection of 10 mg. They spread rapidly into the lung parenchyma and occupied large parts of the lung at 8 weeks after the 25-mg dose. Although highly proliferative, these squamous cell tumors appeared histologically benign and were not readily transplantable during the first 3 months after MCA application. However, between 5 and 7 months after the 25-mg dose, loss of differentiation and marked atypia were noted, and metastasis finally occurred.
Interesting idea, but case not proved
Authors: M. Pringle
Journal: BMJ (1997)

Objective: To evaluate the immunogenicity and reactogenicity of a new triple S recombinant hepatitis B vaccine in a cohort of healthy people in whom currently licensed hepatitis B vaccines had persistently not induced an immune response.Design: Single centre, randomised, double blind, dose-response study.Setting: Research vaccine evaluation centre at a teaching hospital.Subjects: 100 healthcare workers aged 18-70 years with a history of failure to seroconvert after at least four doses of a licensed hepatitis B vaccine containing the S component.Intervention: Each subject was randomly allocated two doses of 5, 10, 20, or 40 g of a new hepatitis B vaccine two months apart.Main outcome measures: Immunogenicity of the four doses.Seroconversion and seroprotection were defined as an antibody titre > 10 IU/l and > 100 IU/l respectively against an international antibody standard.Results: 69 subjects seroconverted after a single dose of the vaccine.After the booster vaccination one other subject seroconverted, bringing the overall seroconversion rate to 70%.Fifteen subjects given 5 g of vaccine, 19 given 10 g, 16 given 20 g, and 20 given 40 g seroconverted.Seroconversion rates in the four antigen dose groups were 60% (15/25), 76% (19/25), 64% (16/25), and 80% (20/25).After the booster dose there was no significant dose-response effect on the overall seroconversion rate, although the small sample size meant that a clinically important dose-response could not be ruled out. Conclusion:A single dose of 20 g of the vaccine was as effective as two doses of either 40 g or 20 g of this vaccine formulation in terms of seroconversion, seroprotection, and geometric mean titres.
Behavior of Two Cell Strains Derived From Rat Rhabdomyosarcomas&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;3&lt;/xref&gt;
Authors: P K BASRUR, J P GILMAN
Journal: JNCI Journal of the National Cancer Institute (1963)

Cells from rat rhabdomyosarcomas have been serially cultured in Connaught's H597 growth medium supplemented with 20 percent calf serum, 0.08 percent sodium bicarbonate, and 100 IU per ml of potassium penicillin G. One cell strain (ALA), derived from a nickel sulfide-induced tumor, has been propagated since February, 1961, while another strain (#79), obtained from a similar tumor, has been maintained since September, 1961. The primary cultures and the early subcultures of these 2 strains were morphologically identical in that both exhibited a loose net of pleomorphic cells reminiscent of early mesenchyme. Subsequently, the ALA strain changed its morphological pattern to fibroblast-like cells of uniform size forming a heavily packed monolayer or multilayer, while #79 strain still remains unchanged. In the primary cultures of ALA strain, 12 percent of the mitotic cells had the normal diploid rat complement, the remaining cells being heteroploids. The percentage of diploids in ALA strain increased to over 50 percent after the first 5 months, and this strain continues to this day (June 25, 1962) to be predominantly diploid. The primary cultures of strain #79 had only 3 percent diploid cells, and this strain is still predominantly heteroploid. The primary ALA culture cells produced sarcomas when injected intramuscularly into weanling Fischer rats; however, cells from the subsequent subcultures failed to produce tumors. The heteroploid strain, #79, consistently produced sarcomas in rats when injected through intramuscular or intraperitoneal routes. The difference in the morphological, chromosomal, and malignant traits of these 2 strains and the possible mechanisms involved in the evolution of a "normal" cell strain (ALA) from a histologically characteristic rhabdomyosarcoma tissue are discussed.