Artemin stimulates oncogenicity and invasiveness of endometrial carcinoma cells

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Endometriosis and endometrial carcinoma

The condition of endometriosis has similar features to endometrial carcinoma, such as enhanced proliferation, decreased apoptosis, cell invasion and compromised function of various organs and it is associated with a heightened risk for malignant transformation. According to Virchow’s theory, inflammation-driven carcinoma may well apply to carcinomas developing in endometriosis [27]. The association between endometriosis and ovarian carcinomas in epidemiologic studies suggest the malignant potential of endometriosis [28]. Endometriosis may be the precursor for the majority of endometrioid and clear-cell ovarian carcinomas [28]. Molecular events such as deregulation of PTEN, TP53, oestrogen, progesterone, and androgen receptors during malignant transformation and development of endometriosis are closely associated [25]. Involvement of pro-apoptotic, anti-apoptotic, and signal transduction genes in endometriosis share similar genetic signatures as carcinomas [25].

FIGO surgicopathological staging of endometrial carcinoma

Generally, endometrial carcinomas which are diagnosed at an early stage (I/II) of the disease are treated with surgery followed by radiation, which results in good prognosis [1]. Surgery and chemotherapy are not sufficient to produce long-lasting tumor regression in patients who are at high risk for recurrence and/or metastasis including those with deep-myometrial invasion, in higher-stage (III/IV) disease, or in high-risk cellular histologic types of endometrial carcinoma (see Table 2 for surgical staging) [1].

Hormonal therapy or cytotoxic chemotherapy

Hormonal therapy or cytotoxic chemotherapy remains a mainstay systemic therapy for recurrent and metastatic endometrial carcinoma [29]. Patients with lowgrade disease with estrogen receptor (ER)-positive and progesterone receptor (PR)- positive carcinoma have a tendency to respond well to hormonal therapy as to cytotoxic chemotherapy, with minimal side effects [29]. Hormonal therapy may also be prioritised in patients with poor prognosis status and/or multiple medical comorbidities
[29]. Cytotoxic chemotherapy is more appropriate as an initial therapy for patients with high grade disease [29]. However, the response rates with progression free intervals are approximately 4 to 6 months with median overall survival in the range of 12 months [30]. Anthracyclines, platinum compounds, and taxanes are the most active classes of chemotherapy agents in metastatic endometrial carcinoma, which produce response rates of greater than 20% [31]. Furthermore, the response range of progression free intervals was increased from 33% to 57% with treatment in combination of these cytotoxic chemotherapeutic agents, with enhanced side effects (Table 3 ) [1].

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Chapter 1. General introduction
1.1. Endometrium
1.2. Growth factors
1.3. Growth hormone
1.4. Artemin
1.5. Hypothesis and aims
Chapter 2. Materials and methods
2.1. Chemicals and reagents
2.2. Cell culture‐
2.3. Molecular biology methods
2.4. Protein methods
2.5. Dialysis and concentrating antibodies
2.6. Xenograft analyses:
2.7. Patients and specimens analysis
2.8. Bioinformatics tools
Chapter 3. Autocrine human growth hormone stimulates oncogenicity of endometrial carcinoma cells
3.1. Introduction .
3.2. Material and methods
3.3. Results
3.4. Discussion .
Chapter 4. Artemin stimulates oncogenicity and invasiveness of endometrial carcinoma cells
4.1. Introduction
4.2. Materials and methods
4.4. Discussion
Chapter 5. Artemin reduces sensitivity to doxorubicin and paclitaxel in endometrial carcinoma cells through specific regulation of CD24 .
5.1. Introduction
5.2. Materials and methods
5.3. Results
Chapter 6. Conclusion and future directions
References
Appendices .