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Supplementary Data 4 from Integrating Global Gene Expression and Radiation Survival Parameters across the 60 Cell Lines of the National Cancer Institute Anticancer Drug Screen

Supplementary Table 3 from A Cell Proliferation and Chromosomal Instability Signature in Anaplastic Thyroid Carcinoma

Supplementary Data 3 from Integrating Global Gene Expression and Radiation Survival Parameters across the 60 Cell Lines of the National Cancer Institute Anticancer Drug Screen

Supplementary Data 2 from Integrating Global Gene Expression and Radiation Survival Parameters across the 60 Cell Lines of the National Cancer Institute Anticancer Drug Screen

Supplementary Figure 1 from A Cell Proliferation and Chromosomal Instability Signature in Anaplastic Thyroid Carcinoma

The 60 cell lines of the National Cancer Institute Anticancer Drug Screen (NCI-60) constitute the most extensively characterized in vitro cancer cell model. They have been tested for sensitivity to more than 100,000 potential chemotherapy agents and have been profiled extensively at the DNA, RNA, protein, functional, and pharmacologic levels. We have used the NCI-60 cell lines and three additional lines to develop a database of responses of cancer cells to ionizing radiation. We compared clonogenic survival, apoptosis, and gene expression response by microarray. Although several studies have profiled relative basal gene expression in the NCI-60, this is the first comparison of large-scale gene expression changes in response to genotoxic stress. Twenty-two genes were differentially regulated in cells with low survival after 2-Gy γ-rays; 14 genes identified lines more sensitive to 8 Gy. Unlike reported basal gene expression patterns, changes in expression in response to radiation showed little tissue-of-origin effect, except for differentiating the lymphoblastoid cell lines from other cell types. Basal expression patterns, however, discriminated well between radiosensitive and more resistant lines, possibly being more informative than radiation response signatures. The most striking patterns in the radiation data were a set of genes up-regulated preferentially in the p53 wild-type lines and a set of cell cycle regulatory genes down-regulated across the entire NCI-60 panel. The response of those genes to γ-rays seems to be unaffected by the myriad of genetic differences across this diverse cell set; it represents the most penetrant gene expression response to ionizing radiation yet observed. [Cancer Res 2008;68(2):415–24]

Supplementary Table 4 from A Cell Proliferation and Chromosomal Instability Signature in Anaplastic Thyroid Carcinoma

Supplementary Table 5 from A Cell Proliferation and Chromosomal Instability Signature in Anaplastic Thyroid Carcinoma

Supplementary Table 1 from A Cell Proliferation and Chromosomal Instability Signature in Anaplastic Thyroid Carcinoma

Supplementary Table 2 from A Cell Proliferation and Chromosomal Instability Signature in Anaplastic Thyroid Carcinoma

Supplementary Figure 1 from Integrating Global Gene Expression and Radiation Survival Parameters across the 60 Cell Lines of the National Cancer Institute Anticancer Drug Screen

Here, we show that the anaplastic thyroid carcinoma (ATC) features the up-regulation of a set of genes involved in the control of cell cycle progression and chromosome segregation. This phenotype differentiates ATC from normal tissue and from well-differentiated papillary thyroid carcinoma. Transcriptional promoters of the ATC up-regulated genes are characterized by a modular organization featuring binding sites for E2F and NF-Y transcription factors and cell cycle–dependent element (CDE)/cell cycle gene homology region (CHR) cis-regulatory elements. Two protein kinases involved in cell cycle regulation, namely, Polo-like kinase 1 (PLK1) and T cell tyrosine kinase (TTK), are part of the gene set that is up-regulated in ATC. Adoptive overexpression of p53, p21 (CIP1/WAF1), and E2F4 down-regulated transcription from the PLK1 and TTK promoters in ATC cells, suggesting that these genes might be under the negative control of tumor suppressors of the p53 and pRB families. ATC, but not normal thyroid, cells depended on PLK1 for survival. RNAi-mediated PLK1 knockdown caused cell cycle arrest associated with 4N DNA content and massive mitotic cell death. Thus, thyroid cell anaplastic transformation is accompanied by the overexpression of a cell proliferation/genetic instability-related gene cluster that includes PLK1 kinase, which is a potential molecular target for ATC treatment. [Cancer Res 2007;67(21):10148–57]

Supplementary Data 1 from Integrating Global Gene Expression and Radiation Survival Parameters across the 60 Cell Lines of the National Cancer Institute Anticancer Drug Screen

Hot-iron disbudding of calves is a stressful and painful procedure and leaves a burn wound. Pain management procedures and the effects of hot-iron disbudding on biochemical markers of pain perception and stress response have been widely investigated in recent years. The aim of this study was to investigate the potential effects of pain management and age of the calf on the healing of burn wounds caused by disbudding. 327 healthy female German Holstein calves were included in this randomised, triple-blinded, prospective study. Calves were either disbudded at the age of four to 10 or 15 to 28 days using a gas-powered hot iron. Each calf was randomly allocated to one of nine possible treatment groups (BG). All calves received either the active ingredients to be tested (xylazine hydrochloride with 0.2 or 0.05 mg / kg body mass (BM) intramuscular for sedation, procaine hydrochloride (2 %) each 8 ml locally on both sides subcutaneously (SC) to the cornual nerves, meloxicam with 0,5 mg / kg BM SC for anti-inflammatory purposes) or an identical amount of saline solution (placebo). Calves in the group `thermE` and `ScheinE` received only placebo. In group `ScheinE` disbudding was simulated and in `thermE` it was carried out. The calves were clinically monitored starting one day before and ending 28 days after the procedure and the burn wounds were assessed. Both the rectal temperature and parameters of wound healing changed significantly during the study period and had characteristic profiles over time. Wound healing was not influenced by the different analgesic protocols, indicating that a multimodal analgesia does not pose a risk for wound healing after thermal disbudding. There were no observed differences between the age groups. The results of this study show, that disbudding of young calves and a multimodal pain management protocol does not affect wound healing in calves.Die thermische Zerstörung der Hornanlage (ZHA) von Kälbern stellt einen Eingriff dar, welcher mit Schmerz und Stress verbunden ist und eine Verbrennungswunde hinterlässt. Verschiedene Verfahren der Schmerzausschaltung sowie der Einfluss der thermischen ZHA auf Marker der Schmerz- und Stressreaktion wurden bereits evaluiert. Ziel der vorliegenden Studie war es zu prüfen, inwieweit das Schmerzmanagement selbst oder das Alter der Kälber die Wundheilung thermisch bedingter Wunden nach ZHA beeinflusst. In die randomisierte, dreifach verblindete, prospektive Studie wurden 327 gesunde, weibliche Deutsch-Holstein-Kälber einbezogen. Die ZHA erfolgte entweder zwischen dem vierten und 10. oder dem 15. und 28. Lebenstag mit einem gasbetriebenen Enthornungsgerät. Jedes Kalb wurde einer von neun Behandlungsgruppen (BG) zugelost. Alle Kälber bekamen entweder die zu testenden Wirkstoffe (Xylazinhydrochlorid mit 0,2 oder 0,05 mg/kg Körpermasse (KM) zur Sedation intramuskulär, Procainhydrochlorid (2 %) je 8 ml lokal beidseitig subkutan (SC) an die Rr. cornuales, Meloxicam mit 0,5 mg/kg KM SC zur Entzündungshemmung/Analgesie) oder eine identische Menge an isotoner Kochsalzlösung (Placebo) injiziert. Kälber der Gruppe `thermE` und `ScheinE` erhielten nur Placebo, bei `ScheinE` wurde die ZHA simuliert, bei `thermE` durchgeführt. Die Gruppe `Melo` erhielt nur Meloxicam, `LA` nur Procainhydrochlorid, `Melo-LA` Meloxicam + Procainhydrochlorid, `Seda 0,2` nur Xylazinhydrochlorid, `Seda 0,05-Melo` und `Seda 0,2-Melo ` (Xylazinhydrochlorid + Meloxicam), und `Seda 0,2-Melo-LA` alle zu testenden Wirkstoffe. Die Kälber wurden von einem Tag vor bis 28 Tage nach dem Eingriff klinisch überwacht und die Wunden befundet. Sowohl die inneren Körpertemperatur (IKT) als auch die Merkmale der Wundheilung unterschieden sich signifikant zwischen den einzelnen Untersuchungstagen und zeigten einen zeitlichen Verlauf. Die Wundheilung wurde durch die verschiedenen Analgetika oder deren Kombinationen nicht beeinflusst, eine multimodale Analgesie stellt demnach kein Risiko für die Wundheilung nach ZHA unter Praxisbedingungen dar. Zwischen den Altersgruppen wurden keine Unterschiede in der Wundheilung beobachtet. Die ZHA von Kälbern kann unter Praxisbedingungen demnach bereits früh und unter Ausschöpfung aller analgetischen Möglichkeiten erfolgen.L’ébourgeonnage thermique des veaux est une procédure stressante et douloureuse qui laisse une brûlure. Les procédures de gestion de la douleur et les effets de l’ébourgeonnage thermique sur les marqueurs biochimiques de la perception de la douleur et de la réponse au stress ont été largement étudiés ces dernières années. Le but de cette étude était d’étudier les effets potentiels de la gestion de la douleur et de l’âge du veau sur la cicatrisation des brûlures causées par l’ébourgeonnage. 327 veaux Holstein allemands femelles en bonne santé ont été inclus dans cette étude prospective randomisée en triple aveugle. Les veaux ont été soit ébourgeonnés à l’âge de 4 à 10 jours ou de 15 à 28 jours à l’aide d’un thermocautère à gaz. Chaque veau a été réparti au hasard dans l’un des neuf groupes de traitement possibles (BG). Tous les veaux ont reçu soit les principes actifs à tester (chlorhydrate de xylazine à 0,2 ou 0,05 mg/kg de masse corporelle (BM) par voie intramusculaire pour sédation, chlorhydrate de procaïne (2 %) 8 ml localement des deux côtés par voie sous-cutanée (SC) jusqu’aux nerfs cornuaux , méloxicam à 0,5 mg/kg de masse corporelle SC à visée anti-inflammatoire) ou une quantité identique de solution saline (placebo). Les veaux du groupe « thermE » et « ScheinE » ont reçu uniquement un placebo. Dans le groupe ‹ScheinE’ l’ébourgeonnage a été simulé et dans ‘thermE’ il a été réalisé. Le groupe « Melo » n’a reçu que du méloxicam, le groupe « LA » uniquement du chlorhydrate de procaïne, le grpoupe « Melo-LA » du méloxicam + chlorhydrate de procaïne, le groupe « Seda 0,2 » uniquement du chlorhydrate de xylazine, les groupes « Seda 0,05-Melo » et« Seda 0,2 -Melo » duchlorhydrate de xylazine et du méloxicam), et le groupe « Seda 0,2-Melo-LA » toutes les substances actives à tester. Les veaux ont été suivis cliniquement en commençant un jour avant et en terminant 28 jours après la procédure et les brûlures ont été évaluées. La température rectale et les paramètres de cicatrisation des plaies ont changé de manière significative au cours de la période d’étude et ont eu des profils caractéristiques au fil du temps. La cicatrisation n’a pas été influencée par les différents protocoles analgésiques, ce qui indique qu’une analgésie multimodale ne présente pas de risque quant à la cicatrisation après ébourgeonnage thermique. Aucune différence n’a été observée entre les groupes d’âge. Les résultats de cette étude montrent que l’ébourgeonnage des jeunes veaux et un protocole multimodal de gestion de la douleur n’affectent pas la cicatrisation des veaux.La decornazione termica dei vitelli è una procedura che è associata a dolore e stress e lascia una ferita da ustione. Diversi metodi di analgesia e l’influenza della decornazione termica sui marcatori del dolore e della risposta allo stress sono già stati valutati. Lo scopo del presente studio era quello di esaminare la misura in cui, la gestione del dolore stesso o l’età dei vitelli, influenzi la guarigione delle ferite provocate dopo la decornazione termica. Lo studio randomizzato, in triplo cieco e prospettico ha incluso 327 vitelli sani di razza Holstein tedesca. La decornazione è stata eseguita tra il quarto e il decimo o il quindicesimo e il ventottesimo giorno di vita utilizzando un dispositivo di decornazione a gas. Ogni vitello è stato assegnato a uno dei nove gruppi di trattamento (GT). A tutti i vitelli sono stati iniettati o gli agenti da testare (xilazina cloridrato a 0,2 o 0,05 mg/kg di massa corporea (MC) per via intramuscolare per la sedazione, procaina cloridrato (2 %) 8 ml ciascuno per via locale bilaterale sottocutanea (SC) ai rr. cornuales, meloxicam a 0,5 mg/kg KM SC per antinfiammatorio/analgesia) o una quantità identica di soluzione salina isotonica (placebo). I vitelli nei gruppi `thermE` e `ScheinE` hanno ricevuto solo placebo; la decornazione è stata simulata in `ScheinE` ed eseguita in `thermE`. Il gruppo `Melo` ha ricevuto solo meloxicam, `LA` solo procaina cloridrato, `Melo-LA` meloxicam + procaina cloridrato, `Seda 0,2` solo xilazina cloridrato, `Seda 0,05-Melo` e `Seda 0,2-Melo` (xilazina cloridrato + meloxicam), e `Seda 0,2-Melo-LA` tutti gli agenti da testare. I vitelli sono stati monitorati clinicamente da un giorno prima a 28 giorni dopo la procedura e sono state valutate le ferite. Sia la temperatura corporea interna (TCI) che le caratteristiche di guarigione della ferita differivano significativamente tra i giorni di studio e mostravano un andamento temporale. La guarigione della ferita non è stata influenzata dai diversi analgesici o dalle loro combinazioni; l’analgesia multimodale non rappresenta quindi un rischio per la guarigione della ferita dopo la decornazione in condizioni reali. Non sono state osservate differenze nella guarigione delle ferite tra i gruppi di età. Pertanto, la decornazione dei vitelli in condizioni reali può essere eseguita presto e con l’esaurimento di tutte le possibilità analgesiche.

Signaling pathways oversee highly efficient cellular mechanisms such as growth, division, and death. These processes are controlled by robust negative feedback loops that inhibit receptor-mediated growth factor pathways. Specifically, the ERK, the AKT, and the S6K feedback loops attenuate signaling via growth factor receptors and other kinase receptors to regulate cell growth. Irregularity in any of these supervised processes can lead to uncontrolled cell proliferation and possibly Cancer. These irregularities primarily occur as mutated genes, and an exhaustive search of the perfect drug combination by performing experiments can be both costly and complex. Hence, in this paper, we model the Lung Cancer pathway as a Modified Boolean Network that incorporates feedback. By simulating this network, we theoretically predict the drug combinations that achieve the desired goal for the majority of mutations. Our theoretical analysis identifies Cryptotanshinone, a traditional Chinese herb derivative, as a potent drug component in the fight against cancer. We validated these theoretical results using multiple wet lab experiments carried out on H2073 and SW900 lung cancer cell lines.