5 research outputs found
A phase I safety, pharmacological, and biological study of the farnesyl protein transferase inhibitor, lonafarnib (SCH 663366), in combination with cisplatin and gemcitabine in patients with advanced solid tumors
No full textA phase I pharmacological and biological study of PI-88 and docetaxel in patients with advanced malignancies
No full textPurpose: This study evaluated the safety, toxicity, pharmacological properties and biological activity of PI-88, a heparanase endoglycosidase enzyme inhibitor, with fixed weekly docetaxel in patients with advanced solid malignancies. Experimental design: This was a phase I study to determine the maximal-tolerated dose of escalating doses of PI-88 administered subcutaneously for 4 days per week, along with docetaxel 30 mg/m given on days 1, 8, 15 of a 28-day schedule. Results: Sixteen patients received a total of 42 courses of therapy. No dose-limiting toxicities were observed despite escalation to the highest planned dose level of PI-88 (250 mg/day). Frequent minor toxicities included fatigue (38%), dysgeusia (28.5%), thrombocytopenia (12%), diarrhea (14%), nausea (12%), and emesis (10%) in the 42 courses. No significant bleeding complications were observed. One patient developed a positive anti-heparin antibody test/serotonin releasing assay with positive anti-platelet factor 4/PI-88 antibodies and grade 1 thrombocytopenia in cycle 5, and was withdrawn from the study without any sequelae. PI-88 plasma concentrations (mirrored by APTT) and urinary elimination were linear and dose-proportional. Docetaxel did not alter the pharmacokinetic (PK) profile of PI-88, nor did PI-88 affect docetaxel PK. No significant relationship was determined between plasma or urine FGF-2, or plasma VEGF levels and PI-88 dose/response. Although no objective responses were observed; 9 of the 15 evaluable patients had stable disease for greater than two cycles of therapy. Conclusion: PI-88 administered at 250 mg/day for 4 days each week for 3 weeks with docetaxel 30 mg/m on days 1, 8 and 15, every 28 days, was determined to be the recommended dose level for phase II evaluation. This combination was well tolerated without severe toxicities or PK interactions
A phase I biological and pharmacologic study of the heparanase inhibitor PI-88 in patients with advanced solid tumors
No full textPurpose: PI-88 is a mixture of highly sulfated oligosaccharides that inhibits heparanase, an extracellular matrix endoglycosidase, and the binding of angiogenic growth factors to heparan sulfate. This agent showed potent inhibition of placental blood vessel angiogenesis as well as growth inhibition in multiple xenograft models, thus forming the basis for this study. Experimental Design: This study evaluated the toxicity and pharmacokinetics of PI-88 (80-315 mg) when administered s.c. daily for 4 consecutive days bimonthly (part 1) or weekly (part 2). Results: Forty-two patients [median age, 53 years (range, 19-78 years); median performance status, 1] with a range of advanced solid tumors received a total of 232 courses. The maximum tolerated dose was 250 mg/d. Dose-limiting toxicity consisted of thrombocytopenia and pulmonary embolism. Other toxicity was generally mild and included prolongation of the activated partial thromboplastin time and injection site echymosis. The pharmacokinetics were linear with dose. Intrapatient variability was low and interpatient variability was moderate. Both AUC and C-max correlated with the percent increase in activated partial thromboplastin time, showing that this pharmacodynamic end point can be used as a surrogate for drug exposure, No association between PI-88 administration and vascular endothelial growth factor or basic fibroblast growth factor levels was observed. One patient with melanoma had a partial response, which was maintained for >50 months, and 9 patients had stable disease for >= 6 months. Conclusion: The recommended dose of PI-88 administered for 4 consecutive days bimonthly or weekly is 250 mg/d. PI-88 was generally well tolerated. Evidence of efficacy in melanoma supports further evaluation of PI-88 in phase II trials
One Simple Idea for Startups and Entrepreneurs
No full textFrom award-winning entrepreneur, inventor, and business owner Stephen Key comes the highly anticipated follow-up to his bestseller One Simple Idea
How many times have you seen a product and thought, I know how to make that better? Or not seen a product and thought, How is it that no one has invented this yet? And when haven’t you thought, I need to be my own boss?
You’re thinking the right things. Now, the next step is to take action?and that’s exactly what One Simple Idea for Startups and Entrepreneurs is all about.
Stephen Key, one of the world’s leading experts on getting business ideas off the ground, revealed in his groundbreaking book One Simple Idea just how simple it is to make a fortune by selling or “renting” your great ideas.
Now, he helps you live the entrepreneurial dream by delivering a proven, straightforward process for starting, growing, and running a business?without the need for an MBA or millions of dollars in funding. As an inventor and successful business owner, Key brings a unique and fully rounded perspective to the subject, teaching you how to:
Develop, test, and protect your idea
Plan and launch your business
Manufacture, package, market, sell, and distribute your product
Manage and grow your business
Prepare for and implement your endgame
Key draws on his own experience as a billion dollar inventor to offer how-to’s and other takeaways you can use to get off the ground and into the black. Case studies, tips, and advice from other successful entrepreneurs underscore key principles to make it easier than ever for you to achieve your business and life dreams.
You don’t need millions of dollars or a business, engineering, or manufacturing background to develop, produce, and sell your own product idea. All you need is one simple idea?and the passion to make it happen.
Praise for One Simple Idea
“This book is straight-forward, no-nonsense information for how to start a successful company. Read it!”
?Barbara Corcoran, investor/shark on ABC’s reality hit Shark Tank
“The ideas in this book are key to creating the kind of enterprise that will create hundreds of thousands of jobs in the future. The goal of entrepreneurship is to reduce the risk of failure as detailed in this book.”
?Nolan Bushnell, inventor of Pong® and founder of Atari®
"Kudos!! One Simple Idea for Startups & Entrepreneurs is brilliant !! A must read for those that have the courage to dive into their dreams. This is a true Road Map for those that have the passion to achieve their Freedom. Truly something that I wish would have been there for me 33 years ago."
?Russ Hornsby, toy industry veteran, 2010 Toy of the Year award winner in seven different countries, and creator of hit toys ZhuZhu Pets®, XiaXia Pets®, DeGeDar® and others
“I took one of those simple ideas and turned it into a company that now has its products in over 35,000 doors of retail distribution. With One Simple Idea for Startups & Entrepreneurs, Stephen gives us the tools we need to take an idea from your Head to the Store shelf.”
?Todd Basche, inventor of Word Lock®, the #1 selling word combination lock
“Any inventor or entrepreneur who wants to make money without risking hundreds of thousands in design, manufacturing, warehousing and distribution would be well served to take advantage of the practical wisdom offered up in Stephen’s most recent work, One Simple Idea for Startups & Entrepreneurs.”
?Ron Hazelton, former home improvement editor for ABC’s Good Morning America and leading authority in the do-it-yourself home improvement field
“One Simple Idea for Startups and Entrepreneurs is a MUST read. The process is broken down into steps that makes it simple to follow and gives you a roadmap to Success.”
?Gene Luoma, Inventor of Zip-It Clean®
"Advice is everywhere but good advice is very rare. Stephen Key’ One Simple Idea for Startups & Entrepreneurs is the exception."
?Steve Greenberg, author of Gadget Nation and co-host of Food Network\u27s television program Invention Hunters
“Stephen’s a trailblazer in what is now widely accepted as the emerging field of frugal innovation.”
?Patrick Raymond, Invention Expert for Huffington Post, creator of InventionScore®, and co-host of Invention Hunters on Food Network
“Stephen Key is the real deal. Without his knowledge and willingness to share it, I would not have been able to successfully bring my own product to market. Now readers of One Simple Idea for Startups & Entrepreneurs have the same opportunity to benefit from an education in startups and just how true it is that all it takes is persistence and one simple idea.”
?Nancy Tedeschi, inventor of SnapIt Screw&™ and prize winner of the WalMart Get on the Shelf contest
An easy, important read for practitioner and academic alike. . . . Highly recommended."
?Choic
Sustainability of marketing systems: systeming interpretation of hybrid car manufacturer and consumer communications
No full textThe purpose of this qualitative macromarketing investigation is to explore the issue of the sustainability of marketing systems. Drawing on complex systems thinking, an alternative logic of marketing systems and a methodological basis for interpreting communicated meanings are developed. The alternative logic of marketing systems recognises the unity of a difference between a marketing system and its environment. This insight has become a cornerstone for synthesising the systeming methodology. Systeming comprises the philosophy, the model, and the method of interpreting communication-as-self-observation of marketing system agents. Data, communication by hybrid car manufacturers and consumers, were collected from netnographic sources such as corporate websites, reports posted online, weblogs, and consumer forums. The interpretation of these data was accomplished using systeming procedures, e.g. communication analysis, distinction identification, re-entry description, and logical level tracking.
The systeming analysis of the hybrid car marketer and consumer communications illustrates that meaning-creation in the system is underpinned by purposeful human behaviour in reducing complexity of marketplace experience into a meaningful pattern, sustainability. Both manufacturers and consumers claim to become sustainable in reference to being unsustainable by creating self-referential differences, operating in different interaction contexts, and expanding meaning paradoxes. The interpretation shows that interactive meaning-creation in the system is inherently contradictory. Manufacturers expand (give a logical form to) contradictions through introducing hierarchical meaning structures, temporality, new functions, and communicative transvection. Consumers deal with the contradictions through enriching co-creation experiences and learning the proper continuation of specific hybrid car driving practices.
The significant insight gained from this investigation is that the hybrid car marketing system is not a passive entity; it is the locus of purposefully expanding meanings. Two modes of sustainability with regard to the hybrid car marketing system can be distinguished: the content of communication that denotes enacted meanings of sustainability and the form of communication that indicates how sustainable these sustainability enactments are. The content/form distinction implies that the sustainability of the hybrid car marketing system is a matter of interactive meaning-creation between system agents. The sustainable development process, in at least a mobility domain, is driven by purposeful social interaction rather than static product attributes.
This investigation is innovative because it a) offers a conceptualisation of a marketing system as a meaning flow; b) synthesises and compiles a methodology and method for interpreting communication in a marketing system; c) reveals systemic insights into the hybrid car marketing system; d) characterises the sustainability dimension of the hybrid car marketing system; e) explains a conceptual ground for reconciling the marketing system and society; f) provides a general macromarketing perspective to scrutinise recent conceptual developments in the marketing discipline; g) unifies marketing systems thinking with recent advancements in the marketing discipline, such as the service-dominant logic, and consumer culture theory; and, also, h) provides recommendations for a number of micro-managerial situations from a holistic perspective
