Tumors treatment

Imaging the effects of treatment targeted to a particular signaling pathway is described earlier, and it can be applied to tumors or xenografts that have been transduced with the appropriate reporter construct or to transgenic reporter animal models of cancer. A more widely used variant of this application, particularly in the pharmaceutical industry, is the monitoring of tumor or 

An alternative to reporter imaging, is to image the target of dmg treatment directly. For example, the cell surface RTK HER2 is overexpressed in many 

Ichikawa T, Hogemann D, Saeki Y, Tyminski E, Teiada K, Weissleder R, Chiocca EA, Basilion JP. MRI of transgene expression crarelation to therapeutic gene expression. Neoplasia 2002 4 523 530. 

Blasberg RG, Gelovani J. Molecular-based imaging a nuclear based perspective. (Review) Mol Imaging 2002 1 280-300. 

Edinger M, Cao YA, Homig YS, Jenkins DE, Vemeris MR, Bachmann MH, Negrin RS, Contag CH. Advancing animal models of neoplasia through in vivo bioluminescence imaging. Eur J Cancer 2002 38 2128 2136. 

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Amino-2,3,6-trideoxy-L-hexoses (A-D in Scheme 3.9) occur naturally, forming the gly-cone part of anthracyclinone antibiotics, important in anti-tumor treatment.104... 

Fowler JF. Rapid repopulation in radiotherapy a debate on mechanism. The phantom of tumor treatment—continually rapid proliferation unmasked. Radiother Oncol 1991 22(3) 156-158. 

In animals, the first in vivo experiments were performed with bacterial extracts in a guinea pig sarcoma model by Gratia and Linz [88], and with LPS in mouse primary subcutaneous tumors by Shear and Turner [4], The antitumoral effect of LPS on the growth of subcutaneous or intramuscular tumors has been extensively investigated [61,147-153], On ascitic tumors, treatment with LPS was shown to be efficient in some cases [153-155] while failing in others [61,156],... 

Earlier data with both Oil Red-0 staining and diO-labeled LCM indicated that 9L tumor cells have a much slower LCM uptake than do C6 tumor cells, both in vivo and in vitro (ref. 531). That difference might be a factor in how fast the paclitaxel is consumed and internalized by the tumor cells. A study by Sharma et al- (ref-605) also suggests that 9L tumor is somewhat paclitaxel-resistant. Accordingly, the daily dose of paclitaxel-LCM was adjusted to 960 pg/kg for subsequent 9L tumor-treatment experiments (ref. 532) (see below). 

We applied the similar strategy for ultrasensitive quantification of a clinically important anticancer drug, paclitaxel. Although conventional high-dose therapeutic regiments of paclitaxel has been widely used for solid tumors treatment, severe side effects and acquired drug resistance are becoming major issue in clinical. Numerous... 

Following the results of these two pivotal studies, trastuzumab was approved by the FDA in 1998, the first mAh approved for solid tumor treatment. Its indicated use is in patients with metastatic breast cancer whose tumors overexpress HER2, either as a single agent for patients previously treated with chemotherapy or in combination with paclitaxel as first-line therapy. Thorough baseline cardiac assessment and extreme caution in patient with preexisting cardiac dysfunction is recommended. 

Table 21.3 shows the clinical studies that have been conducted worldwide, with their different applications, showing that therapies intended for monogenic disease treatment are the second most assessed group, after therapies for tumor treatment. The most used vectors in gene therapy clinical studies are viral vectors (68%), and among those, retroviruses and adenoviruses are the viruses of choice. Synthetic vectors were used in 25% of the studies performed, and about 16% correspond to the use of naked plasmid DNA (Table 21.4). 

Electroporation efficiency depends on the parameters of electric pulses that are delivered to the treated cells using specially designed electrodes and electronic devices. In vitro experiments usually employ parallel plate types of electrodes made of inert metals like stainless steel or platinum but needle types of electrodes are also used for tissue electroporation [24,25,27,28] as well as for tumor treatment apphcations [29-32]. There are two types of electroporator devices available devices with voltage output and those with current output. However, a voltage output device seems to be preferable, which is widely used for diverse applications. 

Fig. 3.6 Nanoparticle siRNA delivery for tumor treatment, a N2Atumor-beaiing mice received a single intravenous injection of 40 mg pLuc in RPP-nanoplexes only, with control siRNA or with Luc-specific siRNA. 24 h following administration, tissues were assayed for luciferase activity (n = 5). b Mice were inoculated withN2Atumor cells and left untreated (open squares) or treated every 3 days by tail vein injection with RPP-nanoplexes with control siRNA or VEGF R2-spedflc siRNA at a dose of 40 mg per mouse. Treatment was started when the tumors became palpable (>20mm ). Only VEGF R2-sequence-speciflc siRNA inhibited tumor growth, whereas treatment with control siRNA did not affect tumor growth rate when compared with untreated controls n = 5)...

Brem H, Piantadosi S, Burger PC, et al. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet 1995 345 1008-1012. 

J. L. Sessler, G. Hemmi, B. G. Maiyo, and A. Harriman, SPIE Corf. on Optical Methods for Tumor Treatment and Early Diagnosis Mechanisms and Techniques 1426, 318 (1991). 

Induction of humoral, cellular, and mucosal immunity. For prophylactic vaccination, all three types of immune response should be addressed. Vaccination against diseases caused by viruses or other intracellular pathogens essentially requires a strong induction of cellular immunity, whereas bacteria-borne diseases need a strong induction of the humoral immune response. For therapeutic vaccination, and especially for tumor treatment, a strong induction of cellular immunity is desirable [6]. 

Tumor Treatment group Mean tumor diameter [cm] Median survivai time... 

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