tbuckley/cabot-search huggingface dataset:
Randomised phase III trial of docetaxel/carboplatin vs MIC/MVP chemotherapy in advanced non-small cell lung cancer (NSCLC) - final results of a British Thoracic Oncology Group (BTOG) trial
Authors: P. Lorigan, R. Booton, L. Ashcroft, K. O'Byrne, H. Anderson, M. Nicolson, P. A. Burt, C. Faivre-Finn, N. Thatcher
Journal: Journal of Clinical Oncology (2004)

7066 Background: Phase III studies suggest higher response rates and better survival in patients with NSCLC treated with a combination of cisplatin and docetaxel (DC) compared to older cisplatin based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC/MVP in patients with advanced NSCLC. Methods: 432 patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy and PS 0–2 were randomised to receive either 4 cycles of DC (docetaxel 75mg/m2, carboplatin AUC 6) or 4 cycles of either MIC (mitomycin 6mg/m2, ifosfamide 3gm/m2, cisplatin 50 mg/m2) or MVP (mitomycin 6mg/m2, vinblastine 6mg/m2, cisplatin 50mg/m2), 3 weekly. The primary end-point was 1-year survival, secondary endpoints were response rates, toxicity and QOL (EORTC QLQ-C30, HADS and LC13). Results: 419 patients were eligible and 87 (21%) were of PS2. There were less stage IV (48 v 54%, p=0.26) and PS2 patients (18 v 23%, p=0.28) in the DC arm. The radiological response rate was 33% for both arms (PR=32%, CR=1%). 32% of MIC/MVP and 29% of DC patients had stable disease. 1 and 2 year survival for DC were 32% and 12% and for MIC/MVP were 37% and 9% (p=0.26). Grade 3/4 neutropenia (66 v 40%, p<0.005), infection (19 v 10%, p=0.02), mucositis (8 v 3%, p=0.03) and peripheral neuropathy (8 v 3%, p=0.05) were more common with DC than MIC/MVP. The MIC/MVP arm had significantly worsening overall EORTC score and global health status whereas the DC arm showed no significant change in these. Conclusions: The combination of DC had similar efficacy to MIC/MVP but QOL was better maintained. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Aventis
Chromosome Observations on Three Epithelial-Cell Cultures Derived From Carcinomas of the Human Cervix&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: Nelly Auersperg, Annette P. Hawryluk
Journal: JNCI Journal of the National Cancer Institute (1962)

Epithelial cultures were grown from biopsies of 3 invasive squamous carcinomas of the cervix and observed in vitro for 6, 9, and 10 months, respectively. The 3 tumors differed clinically in their growth pattern and radio-sensitivity, and histologically, in their degree of differentiation. In vitro, each had a characteristic growth pattern, particularly in respect to cell morphology, cohesiveness, and stratification. When grown in cellulose sponge, the histologic features resembled squamous carcinoma. The 3 cultures had modal chromosome numbers of 45, 51, and 120–130, respectively. The culture with 45 chromosomes had an extra #3, and an additional abnormal large metacentric; one #2, one #16–18, and either one #6–12 + X or one #13–15 were absent. In the culture with 51 chromosomes, one #3 was absent; there were 5 extra #6–12 + X, and 1 extra #19–20. The culture with the modal number of 120–130 had many grossly abnormal chromosomes and a relative excess of metacentrics. These chromosome patterns were identical on several occasions, and also in different sublines within each culture.
In high-risk patients, oral nicotinamide reduced number of new nonmelanoma skin cancers during treatment
Authors: Julio Hajdenberg
Journal: Annals of Internal Medicine (2016)

Source CitationChen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med. 2015;373:1618-26. https://pubmed.ncbi.nlm.nih.gov/26488693/AbstractClinical Impact RatingsGIM/FP/GP: Oncology: Dermatology:
A phase I/II trial of irinotecan and whole brain radiation therapy in patients with brain metastases
Authors: A. Y. Chen, J. K. Ryu, D. Lau
Journal: Journal of Clinical Oncology (2005)

1553 Background: Local CNS failure after whole brain radiation therapy (WBRT) is common for brain metastases. Irinotecan is a topoisomerase I-targeted drug with bioavailability in CNS. Irinotecan also exhibits S-phase-specific cytotoxicity and radiosensitization in a variety of cancers. A Phase I/II study of irinotecan and WBRT was conducted to assess the feasibility, toxicity and efficacy for patients with brain metastases. Methods: Patients with brain metastases from histologically documented solid tumors, KPS ≥70, life expectancy of ≥3 months and ability to participate mini-mental status examination (MMSE) were enrolled. For patients on CYP3A4 inducers, the inducers were stopped before initiating treatment on this study. A total of 37.5 Gy of standard WBRT was given in 2.5 Gy daily fractions. In addition, patients received three weekly irinotecan IV infusions, 0 to 4 hrs before RT on days 1, 8, and 15. In the Phase I study, using the modified Fibonacci dose escalation design, irinotecan dose was started at 60 mg/m2 and escalated in 20 mg/m2 increments until the maximum tolerated dose (MTD) was reached. Results: 14 patients (median age= 60, range 39–75; M/F= 5/9) were enrolled in the Phase I of the study. Treatment was well tolerated at the first two dose levels of irinotecan (60, 80 mg/m2). At 100 mg/m2, one of six patients developed dose-limiting grade 4 neutropenia. No irinotecan-induced diarrhea has been observed. The irinotecan dose has been escalated to the 4th dose level at 120 mg/m2. Symptomatic improvement with radiographic response, including two CRs, was observed in all patients with brain metastases from a variety of solid tumors. Conclusions: Concurrent irinotecan and WBRT for patients with brain metastases is well-tolerated and exhibiting promising efficacy. The MTD of irinotecan will be combined with WBRT to determine the overall survival and neurocognitive function by the MMSE for RTOG-RPA Class II patients in Phase II. This trial is supported by Pfizer. No significant financial relationships to disclose.
The effect of hormonal therapy for prostate cancer on the electrocardiographic QT interval: phase 3 results following treatment with leuprolide and goserelin, alone or with bicalutamide, and the GnRH antagonist abarelix
Authors: M. B. Garnick, C. M. Pratt, M. Campion, J. Shipley
Journal: Journal of Clinical Oncology (2004)

4578 Background: The electrocardiographic QT interval measures ventricular repolarization, and, if prolonged, may predispose to arrhythmias and sudden death. Preclinically, testosterone (T) deficiency may prolong the QT interval. However, the effect of hormone treatments (HTs) for prostate cancer which induce androgen deficiency (AD) has not been well studied. Methods: Three randomized Phase III studies were conducted that compared the GnRH antagonist abarelix to either goserelin plus bicalutamide (G+B) (Study 1); leuprolide (L) monotherapy (Study 2; Urology 58:756, 2001); or L plus B (L+B) (Study 3; J. Urol 167:1670, 2002) in patients (pts) with prostate cancer undergoing initial HT and included pts with Stage D1/D2 disease, rising PSA, intermittent HT or neoadjuvant HT. Study 1 prospectively evaluated data from 177 pts; Studies 2 and 3 retrospectively evaluated 299 of 520 treated pts. Barzett and Fredericia QT intervals (QTcB, QTcF) were measured at baseline (BL), days(D) 84 and 336 of treatment in Study 1; and at BL and D 169 in Studies 2 and 3. Results: \(\underline{\mathrm{Median\ T\ levels}}\) (ng/mL) at BL, D 85 and 336 in Study 1: G+B: 347; 23; 26, respectively; abarelix: 316, 23, 35. In Studies 2 and 3, T levels at BL and D169: L: 342, 9; L+B: 358, 13; abarelix (pooled): 361,14, respectively. \(\underline{\mathrm{Median\ QTcF\ (msec)\ values}}\) at BL and median change from BL on study are: Study 1: G+B: 402, +18; abarelix: 407, +13 (p=0.018 t-test; 0.015 Wilcoxon rank sum). Study 2 and 3: L: 413, +21; L+B: 417, +9; abarelix: 410, +12 (p values from pairwise comparisons, all NS). \(\underline{\mathrm{Percentage\ of\ pts\ with\ maximum\ change\ in\ QTc\ of\ {>}30\ to\ {<}60\ msec}}\): Study 1: G+B: 46%; abarelix: 39%; Studies 2 and 3: L: 27%; L+B: 26%; abarelix: 17%. \(\underline{\mathrm{Percentage\ of\ pts\ with\ maximum\ change\ in\ QTc\ of\ {\geq}\ 60\ msec:}}\) Study 1: G+B: 8%; abarelix: 2%; Studies 2 and 3: L: 6%; L+B: 0%; abarelix: 4%. Conclusions: HTs which induce AD are all associated with prolongation of the QT interval. These findings should be considered in assessing the risk and benefit of HT, especially in those with BL QT values of >450 msec and who are taking Class IA or III antiarrhythmics. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Praecis Pharmaceuticals, Inc. Praecis Pharmaceuticals, Inc. Praecis Pharmaceuticals, Inc. Praecis Pharmaceuticals, Inc.
Personalized Therapy of Chronic Hepatitis C and B Dually Infected Patients With PEGylated Interferon Plus Ribavirin: A Randomized Study
Authors: M.L. Yeh, C.F. Huang, C.I. Huang, M.Y. Hsieh, J.F. Huang, C.Y. Dai, W.L. Chuang, M.L. Yu
Journal: Clinical Gastroenterology and Hepatology (2015)
Abstract 14055: The CHADS(2) Score is a Useful Predictor of Coronary Arteriosclerosis on 320 Slice CT in Subjects with Chronic and Paroxysmal Atrial Fibrillation
Authors: Masae Uehara, Nobusada Funabashi, Sawako Horie, Hiroyuki Takaoka, Koya Ozawa, Yoshio Kobayashi
Journal: Circulation (2012)

Purpose: In evaluating coronary arteries (CA) by 64-256 slice CT, subjects with atrial fibrillation (AF) are usually excluded. CHADS(2) score is a simple score to evaluate risk of cerebral infarcti...
Screening Siblings for Glaucoma in the UK
Authors: S A Vernon
Journal: Journal of the Royal Society of Medicine (1991)

The current practice and ideals of ophthalmologists when alerting and screening siblings at risk of chronic simple glaucoma were assessed by means of a questionnaire. Seventy-nine per cent of Trent Region consultants responded, and of these, 18% do not attempt to alert siblings of glaucoma sufferers. Those who do rely on the probands to alert their siblings and the high street optometrists to screen. Under more favourable conditions, all respondents would advise screening for siblings over 40 years of age. Fifty-nine per cent would then advocate the letter as the optimum method of communication and 78% would prefer that an ophthalmologist screen this high risk group. In a pilot study of a hospital-based screening service, siblings living within a 15 mile radius of the hospital were invited by letter to attend for screening. Ninety per cent attended, of whom 12.5% required treatment and a further 11% careful observation. The cost of detecting a case of treatable disease by this strategy was estimated at £138.
Real-Time 3D TEE for Diagnosis of Subvalvular Pannus Formation in Mechanical Aortic Valves
Authors: Sahmin Lee, Seung-Pyo Lee, Eun-Ah Park, Mi-Kyeong Hong, Ji-Hyun Kim, Hyung-Kwan Kim, Whal Lee, Yong-Jin Kim, Dae-Won Sohn
Journal: JACC. Cardiovascular imaging (2015)
Sweet potato as an alternative to potato in gestational diabetes mellitus
Authors: Arun Sharma, M Thulasimani
Journal: BMJ (2016)

Bao and colleagues recently found that consumption of higher levels of potato before pregnancy was associated with an increased risk of gestational diabetes, and they suggested substituting potatoes with other vegetables or whole grains to lower this risk.1 We suggest that sweet potato ( Ipomoea batatas (L.) Lam) could be eaten instead of potato. Often …
Clinical experience using fulvestrant in hormone responsive metastatic breast cancer
Authors: D. O. Bauerschlag, C. Schem, W. Jonat, N. Maass
Journal: Journal of Clinical Oncology (2006)

10749 Background: We report our clinical experience using the steroid estrogen receptor antagonist Fulvestrant to treat postmenopausal women with hormone sensitive metastasized breast cancer. We discuss the position of Fulvestrant in the endocrine treatment cascade, taking into account the new application guidelines for aromatase inhibitors. Methods: Data from 16 female patients and one male patient treated with Fulvestrant were analyzed. We describe the time point in the treatment cascade when Fulvestrant was administered and the resulting time to progression (TTP). The reviewed cohort was heterogeneous regarding the initial tumor size, the therapy and the progression of the tumor, respectively. The patients were 54 years of age at the time of diagnosis. The estrogen receptor was positive in all cases. Results: Fulvestrant was usually given as the last step in the endocrine treatment cascade (n = 14). The mean TTP was 5.7 months (n = 13). 3 patients are still under successful treatment with Fulvestrant. No common side effects as usually caused by endocrine therapies with Tamoxifen and aromatase inhibitors were documented. Conclusions: The specific estrogen receptor down-regulator Fulvestrant is a valid and well tolerated endocrine treatment option in heavily pre-treated and metastasized breast cancer patients (TTP 5.7 month). Also in the clinical situation of Tamoxifen resistant tumors, Patients could benefit from Fulvestrant. 3 rd generation aromatase inhibitors are now used for the first-line treatment of breast cancer in postmenopausal women. Shifting the sequential endocrine therapy cascade might need a new positioning of Fulvestrant. No significant financial relationships to disclose.
Proteomic and metabolomic analysis of inhibition of monoacylglycerol lipase (MAGL) in human prostate cancer.
Authors: D. P. Lombardi, Daniel K. Nomura, Benjamin F. Cravatt
Journal: Journal of Clinical Oncology (2010)

e15035 Background: In a screen of serine hydrolases, we previously identified monoacylglycerol lipase (MAGL) as a fatty acid metabolic enzyme that had a 4-fold increased expression in aggressive compared with non-aggressive cancer cell lines. MAGL catalyses the hydrolysis of monoacylglycerols (MAG) to produce free fatty acids (FFA) and glycerol and this reaction is the major mechanism to down-modulate signaling via cannabinoid receptors. We hypothesized that inhibiting MAGL would decrease tumor cell growth and migration in a human prostate cancer cell model. Methods: Comparative quantification of serum hydrolase activities for cancer cell proteomes was analyzed by activity-based proteomic profiling (ABPP). Pharmacologic inhibition of MAGL was achieved with treatment with the MAGL inhibitor, JZL184. Lipids were measured by extracting cell metabolomes and analyzing them by liquid chromatography – mass spectroscopy (LQ-MS). Cell migration assays were performed using Transwell chambers coated with collagen I. The PC-3 xenografts were established by injecting 2 million cells subcutaneously into the flanks of SCID mice. Results: 1. MAGL protein expression was higher in androgen-independent, human prostate cancer cell lines PC-3 and DU145, compared to that in the androgen-sensitive line, LNCaP (p < 0.05). 2. In DU145 cells, treatment with the MAGL-specific inhibitor, JZL184, resulted in increased MAG and decreased MAGE, FFA, and LPA. These cells had decreased cell migration, which was partially rescued by the cannabinoid receptor 1 (CB1) antagonist, rimonabant, and further decreased by the CB1 agonist, WIN55212-2 (p < 0.05). 3. We knocked down the expression of MAGL and KIAA by shRNA, which resulted in decreased cell migration of PC-3 and DU145 in vitro (p < 0.05). 4. In SCID mice, PC-3/shMAGL cells demonstrated decreased subcutaneous tumor growth, compared to parental (PC-3) and control (PC-3/shDPP) cells (both p < 0.05, over 3 weeks of growth). Conclusions: 1. Inhibition of MAGL by the pharmacological inhibitor, JZL184, or by shRNAs decreased prostate cancer growth and migration. Inhibition of this enzyme may be useful as an anti-metabolic strategy in controlling prostate cancer growth and progression. No significant financial relationships to disclose.
Identification of predictive markers of response in colorectal cancer following treatment with dasatinib, an orally active tyrosine kinase inhibitor of <i>ABL</i> and <i>SRC</i>
Authors: Z. A. Wainberg, J. Dering, C. Ginther, A. Anghel, O. Kalous, A. Desai, J. R. Hecht, E. Clark, D. Slamon, R. S. Finn
Journal: Journal of Clinical Oncology (2008)

14688 Background: Elevated levels of Src kinase have been implicated in the malignant potential of colorectal cancer. Dasatinib is an orally active, multi-targeted tyrosine kinase inhibitor of ABL and Src family kinases and is currently being investigated in solid tumors. Pre- clinical studies have identified potential biomarkers associated with response to dasatinib in breast cancer in vitro. Methods: To better understand the potential role of dasatinib in colon cancer, we used a panel of 28 human colon cancer cell lines which have undergone microarray analysis using the Agilent platform to determine their baseline gene expression. Using in vitro proliferation assays, we generated dose response curves and calculated IC50 values. Cell lines were then classified as sensitive and resistant using a cut-off of 100 nM. We then analyzed the microarray data to identify potential genes that are associated with response in vitro. Data matrices were used to select differentially expressed genes that would discriminate between sensitive and resistant cell lines. The data was analyzed using Rosetta Resolver software using both hierarchical and non-hierarchical methods. Results: We identified a 3 gene-set that was able to distinguish sensitive and resistant cell lines. These 3 genes (PTK-7, PLK-2 and PLK-3) all had relatively higher levels of expression in the dasatinib sensitive cell lines as compared to the dasatinib-insensitive cell lines. Interestingly, two of these genes (PLK-2 and PLK-3) are part of the Polo-like kinase family, and have recently been identified as potential targets for cancer therapy themselves. In addition, Src expression was not associated with response. In addition, Src was sequenced in these cell lines and no mutations were identified in the kinase domain. Conclusions: In conclusion, these data (1) suggest a role for dasatinib in the treatment of human colorectal cancer (2) identify potential markers of response and (3) suggest rationale for combining dasatinib with PLK targeted agents. Clinical studies are required to validate these findings. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb
Stem Cell Factor as a Single Agent Induces Selective Proliferation of the Philadelphia Chromosome Positive Fraction of Chronic Myeloid Leukemia CD34+ Cells
Authors: Sarah Moore, David N. Haylock, Jean-Pierre Lévesque, Louise A. McDiarmid, Leanne M. Samels, L. Bik To, Paul J. Simmons, Timothy P. Hughes
Journal: Blood (1998)
Outcome of adolescents with acute lymphoblastic leukemia (ALL) treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocols, 1991–2000
Authors: E. Barry, D. E. Levy, M. A. Goldwasser, M. L. Loh, D. J. Deangelo, S. E. Sallan, L. B. Silverman
Journal: Journal of Clinical Oncology (2006)

9023 Background: Historically, adolescents with ALL have had inferior outcomes compared with younger pediatric patients (pts). Recent studies suggest that older adolescents treated on pediatric protocols have better outcomes than similarly aged pts treated on adult protocols. We report the outcome of adolescents enrolled on two consecutive DFCI ALL Consortium protocols conducted between 1991–2000. Methods: Pts aged 1–18 years (yrs) with newly diagnosed ALL were enrolled on two consecutive protocols, 91–01 (1991–1995) and 95–01(1995–2000). All adolescent pts received 20–30 weeks asparaginase (post-remission consolidation), 18 Gy cranial radiation and doxorubicin (cumulative dose 300 mg/m 2 ). Results: 847 pts were enrolled. Median follow-up was 6.5 yrs. Presenting characteristics and outcome of pts according to age are displayed in the table below. Older pts (age ≥ 10 yrs) were more likely to experience pancreatitis (p=0.007) and thromboembolic complications (p&lt;0.001) from asparaginase, but had similar rates of asparaginase-related allergic events (p=0.21) compared to younger pts. Conclusions: Older adolescents (aged 15–18 yrs) with ALL are more likely to present with T-cell phenotype and TEL/AML1-negative disease than younger children. Despite these biologic differences, older adolescents (aged 15–18 yrs) fared relatively well on DFCI ALL Consortium protocols, with a 5-year EFS of 75 ± 6%. This EFS rate compares favorably to published outcomes for older adolescents treated on other childhood ALL protocols. Although adolescents had an increased risk of asparaginase-related toxicity, this therapy was well-tolerated overall. Based on this experience, we are currently piloting our treatment regimen in adults aged 18–50 yrs. [Table: see text] No significant financial relationships to disclose.
Excess mortality rate associated with hepatitis C virus infection: A community-based cohort study in rural Egypt
Authors: Aya Mostafa, Yusuke Shimakawa, Ahmed Medhat, Nabiel N. Mikhail, Cédric B. Chesnais, Naglaa Arafa, Iman Bakr, Mostafa El Hoseiny, Mai El-Daly, Gamal Esmat, Mohamed Abdel-Hamid, Mostafa K. Mohamed, Arnaud Fontanet
Journal: Journal of Hepatology (2016)
The induction of apoptosis in colorectal cancers by preoperative administration of 5'-deoxy-5-fluorouridine (5'-DFUR) and its prediction from gene expression profile analysis using DNA microarray
Authors: N. Tomita, M. Fukunaga, S. Okamura, H. Ohzato, Y. Takatsuka, M. Shirane, H. Yasuno, K. Mori, M. Fujii, N. Matsuura
Journal: Journal of Clinical Oncology (2004)

3710 Background: In the respect of individualized chemotherapy for the patients with the sensitivity for fluoropyrimidines, we analyzed the induction of apoptosis in the tumors of colorectal cancer patients by preoperative administration of 5'-DFUR, which is an intermediate metabolite of capecitabine and has been widely used in Japan, and also investigated the possibility of the prediction of apoptosis induction by microarray-based analysis in the preoperative biopsy specimens. Methods: 48 preoperative colorectal cancer patients were enrolled in the study, and the first 24 patients were randomized into two groups, 5'-DFUR administration group and a group without administration. The preoperative biopsy specimens, taken endoscopically, were prepared for immunohistochemical and RNA analyses. 5'-DFUR (800mg/day) was administered orally for 14–17 days through the day before the operation. After the operation, resected colorectal cancer specimens were also processed in the same manner. The induction of apoptosis in tumor tissue was evaluated by immunohistochemical staining using anti-single-strand (ss) DNA antibody. The gene expression profiles in the preoperative biopsy specimens were analyzed by microarray systems (GeneChip, Affymetrix). Results: The significant induction of apoptosis was observed in the cases with preoperative 5'-DFUR administration(14/36(39%) in 5'-DFUR group vs. 1/12(8%) in control group). From the learning data of DNA microarray in 19 cases (apoptosis induction (+):10 cases, (-):9 cases), 1525 genes with different expression level were extracted and 23 genes were finally selected to establish the formula predicting apoptosis induction. The validation study for this prediction formula is now going on in an effort to future clinical application. Conclusions: The induction of apoptosis in tumor tissues by preoperative administration of 5'-DFUR was confirmed in colorectal cancer patients. The apoptosis prediction formula could be established using DNA microarray analysis on preoperative biopsy specimens. No significant financial relationships to disclose.