Tumors treatment-induced

A particularly active area of research concerns the elucidation of the mechanisms of refractoriness or resistance to anti-VEGF therapy. Tumor cell-intrinsic or treatment-induced expression of angiogenic factors may be implicated Very recent studies have provided evidence that, at least is some murine models, refractor-inessm to anti-VEGF therapy is related to the ability of the tumor to recruit CDllb+Grl+ myeloid cells, which promote angiogenesis [5]. It remains to be established whether these findings also apply to human tumors. 

Three lipids A have been more intensively studied in animal models, all of them having indirect effects, mediated in vivo by the immune system. For two of them, DT-5461 and ONO-4007, TNF-a is an important mediator acting at the vascular level that provokes tumor necrosis. For the third one, OM-174, the treatment induces the accumulation of IFN-y and EL-1 P in tumors, which activate NOS II transcription in tumor cells that produce autotoxic NO, which then provokes the apoptosis of tumor cells. At the same time this treatment inhibits the production of TGF-pi by tumor cells which reduces the TGF-pi induced immunosuppression and enhances NO production. Acquired immune response, probably completes the tumor regression started by the apoptosis process and, most probably induces specific memory. 

Like patients with breast carcinoma, those with ovarian cancer may benefit from treatment with Herceptin in combination with chemotherapeutic drugs. Herceptin treatment is effective, in both early and advanced stages of ovarian cancer (when the majority of tumor cells express HER-2 protein), for eliminating the potentially more malignant HER-2-positive tumor cells. The effectiveness of Herceptin is based on the affinity of this monoclonal antibody for the extracellular domain of HER-2, which is common as ovarian carcinomas progress. However, a tumor vaccine inducing antibody and/or T-cell immunity to HER-2 epitopes will ultimately provide the most effective means to prevent the emergence of HER-2-positive cells. 

DEHP did not induce forestomach tumors in ICR mice administered approximately 1,171 mg DEHP/kg/ day 2 days/week for 4 weeks and sacrificed after 22 weeks of treatment (Lee et al. 1997). Also in this study, DEHP had no significant effect on the number of forestomach tumors/mouse induced by treatment with benzo[a]pyrene once per week for 4 weeks. Initiation-promotion studies and the role of promotion in the carcinogenicity of DEHP are discussed in Section 3. 5.2 Mechanisms of Toxicity. 

Treatment-induced tumors Since most antineoplastic agents are mutagens, neoplasms (for example, acute nonlymphocytic leukemia) may arise 10 or more years after the original cancer was cured. Treatment-induced neoplasms are especially a problem after therapy with alkylating agents (see p. 387). 

First, the highest appropriate unit cancer risk (UCR) is determined from the tumor data from the most sensitive species, strain, sex, and study (FDA, 2002). Tumor incidences not considered treatment related are omitted from analysis statistical significance is an important tool in evaluating the relationship of treatment to tumor induction. If only one dose was tested and only one type of tumor was induced, then the UCR is defined as the slope of the straight line of tumor incidence versus dose. 

T. Hamaoka. 2002. A pivotal role for CC chemokine receptor 5 in T-cell migration to tumor sites induced by interleukin 12 treatment in tumor-bearing mice. Cancer Res 62 3751. 

On the contrary, tumor cells produce NO in response to lipid A [167, 168], leading to tumor cells apoptosis and tumor regression [169]. In the same time the treatment induced desensitization of macrophages without further NO production, via alteration of NFtcB binding [170]. 

S. linuma, G. Wagnieres, K. Schomacker, M. Bamberg, T. Hasan (1995). The importance of fluence rate in photodynamic therapy with ALA-induced PPIX and BPD-MA in a rat bladder tumor model. In T.J. Dougherty (Ed.), Optical Methods for Tumor Treatment and Detection Mechanisms and Techniques in PDTIV (Proc SPIE., Vol. 2392, pp. 136-140). 

Radiotherapy has a vital role in the curative treatment of many common malignancies, including cancers of the head and neck, prostate, bladder, rectum, lung, cervix, uterus, and breast. There is a radiotherapy dose-response relationship for tumor control at most of these primaiy sites. There is also a steep dose response for normal tissue injury late onset, progressive atrophy, and fibrosis." For the individual patient, the prescribed dose aims to achieve the optimal balance between the risk of cancer recurrence and the risk of treatment-induced complications. Restrictions... 

III trial, the associated death rate was 5%, predominantly in elderly patients with concomitant leukopenia and bacteremia [87 ]. Among patients with colorectal cancer, the presence of the primary tumor and previous episodes of chemotherapy-related diarrhea are susceptibility factors for fluorouracil-associated diarrhea [88 ]. Algorithms have been proposed for assessing and managing treatment-induced diarrhea [70 ]. 

Data presented in Fig. 2a show that the untreated tumors doubled their size in 2-3 days. 3AB (449 mg/kg) alone did not influence the growth kinetics of the non-inadiated tumors. en a fiactionated dose of 16 Gy was given (4 times 4 Gy), a delay in growth of the tumors was induced and this effect was increased significantly by 3AB (Fig. 2a). In combined treatment, delay in the growth of the tumors was also dependent on the 3AB concentration (Fig. 2b). 

From three separate experiments, it was calculated that the specific growth delay (the time interval relative to control tumors which was required to double the volume of tumors measured at (he start of treatment) induced by X-rays and the combination of X-rays and 3AB (449 mg/kg) was about 1.5 and 4 days respectively. At fractionated dose levels of 4 times 8 Gy these figures were about 4 and 8.4 days respectively (Fig. 3). When the dose was increased to 4 times 12 Gy, the average size of the tumors fell to below its value on day zero, but the initial difference between the treatment with and without 3 AB was absent (Fig. 4). Due to severe damage of the skin of the X-irradiated animals examination beyond day 14 was not possible. 

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