tbuckley/cabot-search huggingface dataset:
Predictive computer simulations of tumor drug response demonstrate that 3-D hypoxic gradients significantly increase drug resistance
Authors: V. Cristini, H. Frieboes, J. Fruehauf
Journal: Journal of Clinical Oncology (2006)

2071 Background: We created a three-dimensional physiologically based computer (in-silico) model of cancer based on a description of biological events at the cellular scale with input variables determined from patient specific information, such as in-vitro drug response experiments and in-vivo tumor imaging, with the long term goal of individualized treatment selection. The central hypothesis is that such a model that incorporates basic tumor growth kinetics information is capable of representing and predicting tumor response to chemotherapy. Methods: We measured in-vitro tumor growth and drug response for Doxorubicin sensitive and resistant MCF-7 breast cancer cells through trypan blue exclusion counts, tridiated thymidine incorporation, and the XTT assay. We used these results of parameter-based statistics to define input variables to our in-silico model of cancer, and ran computer simulations to measure the drug response predicted by the model. Results: The computer model could accurately predict the in-vitro response of drug sensitive and resistant MCF-7 breast cancer cells. The model also predicted that gradients of oxygen and nutrient in a tumor microenvironment, whether naturally occurring or induced by treatment, and which in previous work we found could increase the invasive capability of tumor cells and destabilize tumor morphology, could also contribute to acquired drug resistance by increasing the population of quiescent cells. Conclusions: We demonstrated that a rigorously, experimentally calibrated computer model of cancer is accurately predictive of in-vitro tumor response to chemotherapeutic drugs, and established that this model offers a means to quantitatively study tumor drug response. We did this through a grounds-up physical representation of tumor biology, not by fitting to experimental data. This validation begins the path to computational modeling and more efficient prediction of in-vivo tumor response to chemotherapy. No significant financial relationships to disclose.
The Virtual Physiological Human: Ten Years After
Authors: Marco Viceconti, Peter Hunter
Journal: Annual Review of Biomedical Engineering (2016)

Biomedical research and clinical practice are struggling to cope with the growing complexity that the progress of health care involves. The most challenging diseases, those with the largest socioeconomic impact (cardiovascular conditions; musculoskeletal conditions; cancer; metabolic, immunity, and neurodegenerative conditions), are all characterized by a complex genotype-phenotype interaction and by a "systemic" nature that poses a challenge to the traditional reductionist approach. In 2005 a small group of researchers discussed how the vision of computational physiology promoted by the Physiome Project could be translated into clinical practice and formally proposed the term Virtual Physiological Human. Our knowledge about these diseases is fragmentary, as it is associated with molecular and cellular processes on the one hand and with tissue and organ phenotype changes (related to clinical symptoms of disease conditions) on the other. The problem could be solved if we could capture all these fragments of knowledge into predictive models and then compose them into hypermodels that help us tame the complexity that such systemic behavior involves. In 2005 this was simply not possible-the necessary methods and technologies were not available. Now, 10 years later, it seems the right time to reflect on the original vision, the results achieved so far, and what remains to be done.
Prognostic value of epidermal growth factor receptor (EGFR) family members in breast cancer.
Authors: T. Badovinac Crnjevic, J. Jakic-Razumovic, D. Vrbanec, A. Juretic, S. Plestina, P. Podolski, B. Sarcevic, N. Saric
Journal: Journal of Clinical Oncology (2010)

e21079 Background: The EGFR tyrosine kinase family consists of four members: EGFR, c-erbB-2, c-erbB-3 and c-erb B-4. Much interest has been focused recently on its members because of their role in breast carcinogenesis. We have evaluated 181 cases of invasive breast cancer immunohistochemicaly to examine the expression of all four EGFR family receptor proteins.The aim of this study was to clarify the prognostic value of these biomarkers in BC as well as to define their relationships with the existing clinicopathological features. Methods: Formalin fixed parraffin embedded samples from 181 patients diagnosed with BC from Sep 2002 to Sep 2003 at Clinical Hospital Center Zagreb, Croatia were examined retrospectively. Samples were stained for EGFR, c-erbB-2, c-erbB-3 and c-erb B-4 by immunohistochemistry.The clinical data included patients demographics such as age and race, tumor characteristics including tumor size, histological tumor type and grade, vascular invasion, Ki-67,lymph node stage, time at type of recurrence, time and status of last follow up. Suvival curves were calculated by the Kaplan-Meier method. Association between immunohistochemical findings and other variables were calculated using Spearmans rank correlation test and point-biserial correlation coefficient. Results: Expression of ERGF, erb-2,3,4 was observed in 20.6%, 18.2%, 29.5% and 5.7% respectively. There was significant association between EGFR overexpression and larger tumor (r=.18, p< 0.05), higher grade (r=.23, p< 0.01), more positive nodes (r=.17, p< 0.05), higer Ki-67 (r=.26, p< 0.01). Similar results were obtained for c-erbB-2 overexpression, while no such association existed for c-erbB-3 and e-erbB-4 family members. Tumors overexpressing EGFR and c-erbB-2 had worse 5-years DFS compared to c-erbB-3 and c-erbB-4 tumors (56%, 61%, 78%, 70% respectively). Conclusions: This study shows that tumors overexpressing EGFR and c-erbB-2 are associated with worse clinicopathological features and have significant increase in recurrence. No such association was found for c-erbB-3 and c-erbB-4. EGFR overexpression could provide additional information to perform risk stratification of early breast cancer patients. No significant financial relationships to disclose.
Panitumumab, gemcitabine, and irinotecan in patients with advanced or metastatic cholangiocarcinoma: A phase II study.
Authors: W. Sun, K. Mykulowycz, U. R. Teitelbaum, N. Damjanov, D. G. Haller, B. J. Giantonio, M. Carberry, P. J. O'Dwyer
Journal: Journal of Clinical Oncology (2010)

TPS214 Background: Cholangiocarcinoma is an aggressive neoplasm with rising incidence. Cytotoxic chemotherapy agents have moderate effects either as single agents or combinations. More effective treatments are needed, especially treatments based on molecular cancer characteristics. Overexpression of epidermal growth factor receptor (EGFR) is associated with tumor stage, lymph node metastasis, lymphovascular and perineural invasion of cholangiocarcinoma, and is an independent indicator of poor prognosis (Yoshikawa D, et al. Br J Cancer 2008 98:418-25). A phase II study showed some activity with erlotinib as single agent (Philip P, et al. JCO 2006 24:3069-74); moreover, a small trial suggested that cetuximab may circumvent tumor resistance to chemotherapy (Paule B, et al. Oncology 2007;72:105-10). This ongoing phase II study is designed to evaluate the efficacy and tolerability of adding panitumumab, a monoclonal anti-EGFR antibody, to combined gemcitabine and irinotecan that we previously developed in this disease (Sun W, et al. Cancer 2007 110:2768-74) in patients with advanced and metastatic cholangiocarcinoma. Methods: Patients with advanced unresectable or metastatic cholangiocarcinoma, ECOG PS 0-2, adequate liver, kidney and bone marrow function were treated with panitumumab (9 mg/kg) on day 1, gemcitabine (1000 mg/m2/100 min) iv and irinotecan (100 mg/m2) iv on days 1 and 8 of a 21-day cycle. Tissue specimens were collected based on availability for future biomarker analyses. The primary objective is to evaluate the 5-month progression-free survival (PFS) rate. A true 5-month PFS rate of 65% or more will be taken as evidence of activity in this patient population. Response rate, overall survival rate and tolerability/feasibility are tested also. No significant financial relationships to disclose.
Phase I Study of Paclitaxel, Carboplatin, and Increasing Days of Prolonged Oral Etoposide in Ovarian, Peritoneal, and Tubal Carcinoma: A Gynecologic Oncology Group Study
Authors: Peter G. Rose, Michael Rodriguez, Steven Waggoner, Benjamin E. Greer, Ira R. Horowitz, Jeffrey M. Fowler, William P. McGuire
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Given the activity of prolonged oral etoposide in platinum and paclitaxel-resistant ovarian carcinoma, a phase I trial was conducted that combined increasing days of oral etoposide therapy with paclitaxel and carboplatin in chemotherapy-naive patients with ovarian peritoneal and tubal carcinoma to establish a maximum-tolerated dose (MTD) of this combination. PATIENTS AND METHODS: Paclitaxel at 175 mg/m 2 given over 3 hours and carboplatin at an area under the curve of 5 were administered on day 1 followed by oral etoposide 50 mg/m 2 /d beginning on day 2. The number of days of etoposide therapy was escalated on the basis of toxicity. Toxicity end points included neutropenic sepsis, grade 4 thrombocytopenia, or grade 3 neutropenia or thrombocytopenia during etoposide administration. Cycles were repeated every 21 days for a maximum of six courses. Due to hematologic toxicity, the duration of the paclitaxel infusion was decreased to 1 hour for a second stage of accrual. RESULTS: Of 52 patients studied, 29 were in the first stage of accrual. Dose-limiting toxicity occurred with 8 days of oral etoposide, making the MTD six days of therapy. Twenty-three patients were entered into the second stage of accrual. Dose-limiting toxicity occurred at 12 days of oral etoposide, making the MTD 10 days of therapy. Three patients developed acute myeloid leukemia 16, 27, and 35 months after receiving a cumulative dose of 200 mg/m 2 , 1,200 mg/m 2 , and 2,400 mg/m 2 , respectively. CONCLUSION: One-hour paclitaxel, carboplatin, and oral etoposide at 50 mg/m 2 /d for 10 days is tolerable without supportive therapy. The leukemogenic potential is cause for concern and precludes its use in chemotherapy-naive ovarian carcinoma.
Effect of Strain Differences and Tumor Presence on Microsomal Drug Metabolism in the Guinea Pig: Brief Communication
Authors: Charles L. Litterst, Edward G. Mimnaugh, Theodore E. Gram
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Effect of Strain Differences and Tumor Presence on Microsomal Drug Metabolism in the Guinea Pig: Brief Communication Get access Charles L. Litterst, Charles L. Litterst 2Drug Interactions Section, Laboratory of Toxicology, Experimental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute (NCI), National Institutes of Health, Public Health Service, V.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward G. Mimnaugh, Edward G. Mimnaugh 2Drug Interactions Section, Laboratory of Toxicology, Experimental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute (NCI), National Institutes of Health, Public Health Service, V.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar Theodore E. Gram Theodore E. Gram 2Drug Interactions Section, Laboratory of Toxicology, Experimental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute (NCI), National Institutes of Health, Public Health Service, V.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014. 3We thank Dr. Robert Bast, Biology Branch, NCI, for the tumor inoculum supply and Ms. Charla O'Brien, NCI, for skillful typing of the manuscript. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 6, December 1977, Pages 1737–1739, https://doi.org/10.1093/jnci/59.6.1737 Published: 01 December 1977 Article history Received: 17 March 1977 Accepted: 06 July 1977 Published: 01 December 1977
Ideal Number of Target Lesion Per Organ to Be Measured in Metastatic Colorectal Cancer
Authors: Hyeong Su Kim, Jung Han Kim, Dae Ro Choi, Boram Han, Hunho Song, Geundoo Jang, Jung Hye Kwon, Ho Young Kim, Hyo Jung Kim, Dae Young Zang
Journal: Annals of Oncology (2014)
Improved survival for patients with AIDS-related Kaposi's sarcoma.
Authors: S A Miles, H Wang, R Elashoff, R T Mitsuyasu
Journal: Journal of Clinical Oncology (1994)

We retrospectively analyzed all patients with AIDS-related Kaposi's sarcoma (AIDS-KS) seen at one large California medical center to delineate factors that may have contributed to a relative decline in survival.Potential prognostic factors were analyzed individually, using the Cox proportional hazards regression model, for their association with survival. After a stepwise Cox regression procedure was applied to those factors that showed a significant effect on survival, a subset of factors that best predicted survival was identified. We then quantified the effect of the year of diagnosis on survival using a univariate Cox model. Next, we combined the year of diagnosis with the subset of prognostic factors previously identified into the Cox model to examine survival after adjustment for the prognostic factors. Survival distribution was estimated by the Kaplan-Meier method, and the 95% confidence interval for the median survival was computed using the modified reflected method.In 688 patients, we identified four baseline variables that best predicted survival: CD4 cell number, hematocrit, number of KS lesions, and body mass index (BMI). Adjusted for these predictive factors, there was a significant improvement in survival for patients with AIDS-KS over the last 6 years.Contrary to prior reports, survival has increased for patients with AIDS-KS. The apparent increase in observed mortality is most likely due to a decline in the CD4 cell number at presentation.
Phase II study comparing volociximab (an antiangiogenic antibody) and pegylated liposomal doxorubicin (PLD) with PLD alone in recurrent ovarian or primary peritoneal cancer
Authors: I. B. Vergote, N. Colombo, E. Kutarska, J. Del Campo, C. Pippitt, A. Casado, E. Lengyel, K. Gilder, S. Ho, R. J. Schilder
Journal: Journal of Clinical Oncology (2009)

5560 Background: Volociximab (V), a chimeric monoclonal antibody with direct antitumor effects, blocks α5β1 binding to fibronectin and induces apoptosis in proliferating endothelial cells. A Phase I/II study was performed to evaluate PLD with/without V in patients (pts) with recurrent ovarian or primary peritoneal cancer that relapsed after platinum/taxane-based chemotherapy (maximum 2 prior lines). Methods: A 3-arm adaptive randomization design compared efficacy and safety of PLD (40 mg/m 2 q4wk) + V (15 mg/kg q2wk or qwk) vs. PLD alone. Pts were stratified by platinum sensitivity and received treatment until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Pharmacokinetic (PK) and pharmacodynamic effects were also evaluated. Results: There were 6 iterations of adaptive randomization based on accumulating PFS data. 127 pts were randomized: 66 in Group A (PLD), 34 in Group B (PLD+V [q2wk]), and 27 in Group C (PLD+V [qwk]). The incidence of AEs was balanced across treatment groups. The most common Grade 3/4 AEs (≥5% in any group) were abdominal pain, intestinal obstruction, ascites, fatigue, hypoalbuminemia, and cytopenias. Based on preclinical data, therapeutic levels of V were maintained during treatment, and V did not appear to alter the PK of PLD. Response rates were comparable across groups. There were no CRs; PRs were 16%, 18%, and 19%. The median PFS estimates were 193, 164, and 221 days. Conclusions: The safety profile of V+PLD appeared similar to PLD alone. Preliminary analysis of PFS suggested that there was a low probability of detecting a statistically significant difference in favor of V+PLD, so the study was closed to enrollment. Analyses correlating PFS with platinum sensitivity and α5β1 tumor expression are ongoing. [Table: see text]
Effect of BCG on Dimethylhydrazine Induction of Colon Tumors in Rats<xref ref-type="fn" rid="fn2">2</xref>
Authors: A E Rogers, J Gildin
Journal: JNCI Journal of the National Cancer Institute (1975)

The effect of BCG injection into the colon wall on the induction of colon tumors by 1,2-dimethylhydrazine dihydrochloride (DMH) was assessed in male rats. Persistent, generalized BCG infection followed the intracolonic injection of 6.7 times 10(6) organisms in otherwise untreated rats. In rats given DMH (30 mg/kg/wk) intragastrically for 5 weeks and then infected with BCG, colon tumors developed at the same rate and in the same incidence as in uninfected rats, but more tumors were mucinous adenocarcinomas and metastasized to the abdominal lymph nodes. In a few rats with large, established colon tumors, the injection of BCG into tumors induced no apparent change in them when examined at autopsy 1-22 weeks later.
Reflections on Marriage Equality
Authors: Ian H. Jenkins
Journal: Annals of Internal Medicine (2016)

On Being a Doctor19 January 2016Reflections on Marriage EqualityIan H. Jenkins, MDIan H. Jenkins, MDFrom University of California, San Diego, San Diego, California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-1687 Audio Reading - “Reflections on Marriage Equality” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Reflections on Marriage Equality," by I.H. Jenkins. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail 13: I have my first crush, on a boy named Jeff. I don't know what it means. I do know that no one can ever, ever find out.15: I've never known a gay person in my life. All gay people live in San Francisco and die of AIDS. I have to change or be alone my entire life. I try dating girls. I learn to insult people by calling them faggots. This can work.18: At my university's football games, thousands of fans chant homophobic songs. When I come out in the newspaper, some friends never speak to me ... Author, Article, and Disclosure InformationAffiliations: From University of California, San Diego, San Diego, California.Corresponding Author: Ian H. Jenkins, MD, University of California, San Diego, 6545 Norman Lane, San Diego, CA 92120; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “Reflections on Marriage Equality” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Reflections on Marriage Equality," by I.H. Jenkins. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Cited byHealth Disparities by Sexual Orientation: Results and Implications from the Behavioral Risk Factor Surveillance System 19 January 2016Volume 164, Issue 2Page: 129-130KeywordsAIDSChildrenHIVHealth insuranceHepatitisLGBTQPatent ductus arteriosusResidencySalivaSubstance abuse ePublished: 19 January 2016 Issue Published: 19 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The effect of different dose regimens in intravesical treatment of urinary bladder cancer with gemcitabine: A randomized phase II marker tumor study
Authors: T. Gardmark, M. Carringer, E. Beckman, P.-U. Malmström
Journal: Journal of Clinical Oncology (2005)

4591 Background: Current intravesical treatments of Ta-T1 urinary bladder cancer have shown good efficacy, but improvement is needed. We evaluated the efficacy and toxicity of 3 different dose regimens of gemcitabine administered intravesically to patients with urinary bladder cancer. Methods: Patients with histologically proven stage Ta, grade 1/2 urinary bladder cancer and a marker lesion diameter of 0.5 to 1 cm after transurethral resection were enrolled; they received gemcitabine 2000 mg that was instilled and kept in the bladder for 1 hour. Patients were randomized to one of the following regimens: 1 dose (group A); 2 doses/week for 3 weeks (group B); or 1 dose/week for 6 weeks (group C). Response was assessed via cystoscopy 9 weeks after the end of treatment. Results: Between January 2002 and March 2004, 32 patients were enrolled; 2 were excluded due to protocol violations (groups B and C). Of the 30 randomized patients (11, group A; 10, group B; 9, group C), 1 patient was not evaluable for efficacy (group A). Nine patients (31%) reported a complete response (1, group A; 4, group B; 4, group C); an additional 9 patients (31%) had no response; and 11 (38%) had a tumor increase. All 30 patients were evaluable for toxicity. No NCI-CTC grade 3/4 toxicity was observed. Grade 1/2 nausea was reported in 5 patients (17%), and grade 1/2 fever in 2 patients (7%). One patient (3%) had grade 1 thrombocytopenia, which was reversible, and 1 of the patients with fever had grade 1 anemia, which was also reversible. Instillations were discontinued due to toxicity for only 1 patient (nausea, fever). Ten patients (33%) were unable to retain the drug for the full hour. Conclusions: As an intravesical instillation, gemcitabine showed activity and was well tolerated. The single-dose regimen does not appear to be effective. Also, twice-weekly doses do not appear to be more effective than once-weekly doses. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly