Peritoneal metastasis mostly originates from the tumors in the neighboring digestive system and organs, such as intestine, stomach, liver, pancreas, etc. Tumor cells accumulate and adhere abundantly on the peritoneum through blood or the lymph node after falling into peritoneal cavity, but do not invade other substantial organs (such as spleen, uterus and ovaries) directly. These tumor cells adhere on the surfaces of these organs, and will proliferate to invade these organs directly for a long time. This is a common phenomenon for cancers in the digestive tract of the peritoneal cavity. For instance, cancers include gastric cancer, small intestine cancer, colon cancer, rectal cancer, appendiceal cancer and pancreatic cancer. Certainly, there are few cancer cells originated from the peritoneum, and this situation is named primary peritoneal surface cancer.
Metastasis in the peritoneal cavity was deemed as an expression manner of the late-stage cancer in the past. Therefore, most of doctors in oncology only administrated an assistant or a remissive treatment, such as radiotherapy, anti-cancer chemotherapy and immunotherapy, etc. However, immunotherapy dose not yet have a concrete result acceptable for everybody. Most of patients appear the phenomena of ascites accumulation and intestinal obstruction, so as to lead to extreme pain and starvation.
If active treatment is not administrated, these patients diagnosed the peritoneal metastasis in the peritoneal cavity only have several months to live (average survival rate is 5 to 6 months). Among this, colorectal peritoneal carcinomatosis is deemed as a disease treated with relaxation therapy before death.
In the past decade, some new therapies, including active cyto-reductive surgery combining with hyperthermic intraperitoneal chemotherapy, have shown that these therapies can improve the average post-operative survival rate to 32.4 months (Glehen et al., J. Clin. Oncol., 2004). This strategy seems to bring a hope to the late-stage cancer patients with peritoneal metastasis. However, with regard to the researches of the active cyto-reductive surgery supplemented with hyperthermic intraperitoneal chemotherapy, more than 50% researches are still shown that the post-operative mortality of this strategy is 5% high (Glehen et al., Lancet Oncol., 2004; Koppe et al., 2006; Yan et al., 2006), and the incidence is ranged between 25% and 35% (Glehen et al., J. Clin. Oncol., 2004; Glehen et al., Lancet Oncol., 2004; Koppe et al., 2006; Yan et al., 2006; Verwaal et al., 2003; Glehen et al., 2003). This strategy only has effect on the early-stage cancer patients. Therefore, researching the mechanism of peritoneal metastasis and developing new therapies are urgently needed to the late-stage cancer patients with peritoneal metastasis.
In the progress of the peritoneal cavity cancer patients (including colorectal cancer, gastric cancer and ovary cancer, etc.), in order to absorb more nutrients, cancer cells usually proceed the peritoneal metastasis. At this time, cancer cells must adhere and invade the mesothelial layer, proliferate and begin angiogenesis. Therefore, the behavior that cancer cells adhere on the surface of peritoneum can be deemed as the key point in the beginning of peritoneal metastasis.
The adhesion ability of cancer cells can be regulated by the amount of connective tissue growth factor (CTGF). CTGF is an extracellular matrix-associated molecule (Rocnik et al., 2006; Bornstein et al., 2000; Bornstein et al., 2002), and CTGF has been proved to influence various important cellular functions, such as regulation of mitosis, apoptosis, generation of extracellular matrix, angiogenesis and metastasis (Lau et al., 1999; Bork et al., 1993; Moussad et al., 2000; Brigstock et al., 1999; Perbal 2001; Babic et al., 1999; Planque et al., 2003). Recently, many researches are also shown that CTGF can enhance the adhesion of different normal cells, such as fibroblasts, platelets, endothelia cells and rat hepatic stellate cells (Babic et al., 1999; Gao et al., 2004; Chen et al., 2001; Jedsadayanmata et al., 1999). However, the regulation mechanism of CTGF adhering to cancer cells are not completely clarified.
Taiwanese Patent No. 1282419 has been disclosed that the amount of CTGF represents the inverse correlation with the possibility of invasion or metastasis in the lung cancer patients. U.S. Patent Application No. 2005/0147986 is further disclosed that the truncation of the constructed CTGF plasmid is performed to identify the active fragment of CTGF, and is further founded that the inhibition effect of the C-terminal (CT) domain-lacked CTGF to the cancer cells will decrease enormously.
Therefore, in order to clarify whether CTGF can change the activity of peritoneal dissemination of cancer cells, the possible regulation mechanism of CTGF to the cancer cell adhesion is further researched in the present invention. Furthermore, the possible relationship between CTGF and peritoneal metastasis recurrence is further researched in the present invention.
It is therefore attempted by the applicant to deal with the above situation encountered in the prior art.
USPTO Backgrounds
USPTO Backgrounds