Cancer log-kill revisited.

نویسنده

  • Larry Norton
چکیده

At the root of science lie basic rules, if we can discover or deduce them. This is not an abstract project but practical; if we can understand the why then perhaps we can rationally intervene. One of the unifying unsolved problems in physics is the hypothetical "Theory of Everything." In a similar vein, we can ask whether our own field contains such hidden fundamental truths and, if so, how we can use them to develop better therapies and outcomes for our patients. Modern oncology has developed as drugs and translational science have matured over the 50 years since ASCO's founding, but almost from that beginning tumor modeling has been a key tool. Through this general approach Norton and Simon changed our understanding of cancer biology and response to therapy when they described the fit of Gompertzian curves to both clinical and animal observations of tumor growth. The practical relevance of these insights has only grown with the development of DNA sequencing promising a raft of new targets (and drugs). In that regard, Larry Norton's contribution to this year's Educational Book reminds us to always think creatively about the fundamental problems of tumor growth and metastases as well as therapeutic response. Demonstrating the creativity and thoughtfulness that have marked his remarkable career, he now incorporates a newer concept of self-seeding to further explain why Gompertzian growth occurs and, in the process, provides a novel potential therapeutic target. As you read his elegantly presented discussion, consider how this understanding, wisely applied to the modern era of targeted therapies, might speed the availability of better treatments. But even more instructive is his personal model-not only the Norton-Simon Hypothesis-of how to live and approach science, biology, patients and their families, as well as the broader community. He shows that with energy, enthusiasm, optimism, intellect, and hard work we can make the world better. Clifford A. Hudis, MD, FACP, 2013-2014 ASCO President.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Theoretical concepts and the emerging role of taxanes in adjuvant therapy.

The proven benefits of adjuvant chemotherapy on disease-free and overall survival in breast cancer can be explained by concepts of cell kill. Interventions which result in greater log kill can be expected to produce improved clinical results. The application of log-kill concepts to human breast cancer growth, which appears to follow Gompertzian kinetics, suggests not only that the use of non-cr...

متن کامل

Therapeutic synergy of oral taxane BMS-275183 and cetuximab versus human tumor xenografts.

PURPOSE Combination therapy consisting of an oral taxane, BMS-275183, and the anti-epidermal growth factor receptor monoclonal antibody, cetuximab, was assessed for enhanced therapeutic benefit in preclinical tumor models. EXPERIMENTAL DESIGN Mice bearing human tumor xenografts, either L2987 lung or GEO colon carcinoma, were administered the aforementioned treatments singly or in combination ...

متن کامل

Improved therapeutic index with high-dose methotrexate: comparison of thymidine-purine rescue with citrovorum factor rescue in mice.

Two biochemically different rescue agents, citrovorum factor (CF) and thymidine-inosine-allopurinol (TIA), were compared in an attempt to identify the mechanism for the increased therapeutic index achieved with high-dose methotrexate (MTX) plus rescue. Both CF and TIA were capable of protecting mice from MTX dosages up to 2000 mg/kg. Treatment of L1210-bearing mice with 2000 mg/kg MTX plus CF o...

متن کامل

Impact of Glycopeptide Resistance in Staphylococcus aureus on the Dalbavancin In Vivo Pharmacodynamic Target.

Dalbavancin is a novel lipoglycopeptide with activity against Staphylococcus aureus, including glycopeptide-resistant isolates. The in vivo investigation reported here tested the effects of this antibiotic against seven S. aureus isolates with higher MICs, including several vancomycin-intermediate strains. Results of 1-log kill and 2-log kill were achieved against seven and six of the isolates,...

متن کامل

Cutting edge: the tumor counterattack hypothesis revisited: colon cancer cells do not induce T cell apoptosis via the Fas (CD95, APO-1) pathway.

The counterattack hypothesis, suggesting that cancer cells express Fas ligand (FasL) and are able to kill Fas-expressing tumor-infiltrating activated T cells, was supported by reports of the killing of Jurkat cells by FasL-expressing human colon cancer cell lines. Through the use of an improved cytotoxic assay in which soluble FasL and FasL-transfected KFL9 cells were used as positive controls,...

متن کامل

Comparison of hydrogen peroxide contact lens disinfection systems and solutions against Acanthamoeba polyphaga.

Acanthamoeba is a free-living amoeba causing a potentially blinding infection of the cornea. Contact lens wearers are most at risk and account for some 95% of cases. Hydrogen peroxide is used for contact lens disinfection due to its broad antimicrobial activity. Lenses must be neutralized before use to avoid pronounced stinging and possible corneal damage. Neutralization is achieved by adding a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Meeting

دوره   شماره 

صفحات  -

تاریخ انتشار 2014