Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-metastatic efficacy of MMI-166, which is a selective matrix metalloproteinase (MMP) inhibitor, in combination with CPT-11 was examined using two metastasis models of human gastrointestinal cancer cells. In the liver metastasis model, C-IH human colon cancer cells were injected into the spleen of athymic BALB/c nude mice. Daily oral (p.o.) dosing of MMI-166 at 200 mg/kg starting 1 day after tumor inoculation led to a significantly prolonged survival effect by inhibiting liver metastasis of C-1H tumor cells. CPT-11 (5 or 20 mg/kg) was administered intraperitoneally (i.p.) three times on day 3, day 7 and day 11 and also improved the survival of tumor-inoculated mice compared with the vehicle control. When MMI-166 was combined with CPT-11, the anti-metastatic efficacy was significantly augmented. Moreover, long tumor-free survival was noted in two of eight mice that were given the combination therapy but not either MMI-166 or CPT-11 monotherapy. In the peritoneal dissemination model, TMK-1 human gastric cancer cells were injected i.p. into nude mice. While both MMI-166, administered daily p.o. from day 1 at 200 mg/kg, and CPT-11, administered intravenously (i.v.) three times, inhibited the tumor dissemination and growth, the combination therapy of MMI-166 plus CPT-11 showed a greater inhibitory effect than each monotherapy. A hematotoxicity study demonstrated that CPT-11 alone significantly decreased the number of white blood cells (WBC) and bone marrow cells (BMC) in the mice during treatment, while the daily administration of MMI-166 alone had no such effect. More importantly, the combination therapy of MMI-166 with CPT-11 did not augment the hematotoxicity caused by CPT-11. An in vitro cytotoxicity study showed that MMI-166 itself neither has direct cytotoxicity in C-1H and TMK-1 tumor cells, nor does it augment the cytotoxicity of SN-38, an active form of CPT-11. The findings indicate that the augmented anti-metastatic efficacy in combination treatment was not simply due to the augmentation of direct cytotoxic activity, but was rather an additive or synergistic effect of anti-metastatic activities with different mechanisms. In conclusion, we demonstrated that the anti-metastatic efficacy against C-1H colon cancer and TMK-1 gastric cancer were augmented by the combination therapy of MMI-166, an orally active MMP inhibitor, with CPT-11. However, the hematotoxicity caused by CPT-11 was not augmented in the combination with MMI-166. Thus, the combination therapy of MMI-166 and CPT-11 exhibited potent anti-metastatic efficacy without increased hematotoxicity. These results point to the clinical advantage of using MMI-166 in combination with CPT-11.
Clin Exp Metastasis 2002
PMID:Augmented anti-metastatic efficacy of a selective matrix metalloproteinase inhibitor, MMI-166, in combination with CPT-11. 1240 89

Sentinel node navigation surgery (SNNS) for gastrointestinal cancer has been examined using various methods, but the SN concept has not been established. For 18 patients who had colorectal cancer without macroscopic nodal metastases, we had attempted to detect sentinel lymph nodes (SNs) with activated carbon particles and investigate the existence of nodal metastases histologically. SNs were detected in 17 of 18 patients. Thus activated carbon particles are a useful tracer for SN detection. Three patients had microscopic nodal metastases, and two had nodal metastases in SNs. Although the remaining patient was a false negative case which had nodal metastases in non-SNs only, the nodal metastases were within the sentinel lymphatic region (SLR) which includes SNs. It is considered possible to safely perform minimally invasive lymphadenectomy for colorectal cancer without macroscopic nodal metastases, by means of SLR dissection using activated carbon particles.
 ...
PMID:[Detection of sentinel lymphatic region with activated carbon particles in lymph node dissection for colorectal cancer]. 1248 57

Tumor progression after curative resection of gastrointestinal cancer is probably caused by disseminated tumor cells that can be detected in different body compartments, e.g. the peritoneum. The clinical importance and prognostic significance of gross peritoneal metastasis is well known whereas the prognostic relevance of disseminated tumor cells in the peritoneum of patients with gastrointestinal cancer is still unclear. Disseminated tumor cells in the peritoneal cavity are generally detected by cytology, immunohistochemistry or polymerase chain reaction-based molecular methods. A consensus on the most adequate detection method has not yet been found making the comparison of different data difficult. The prognostic relevance of tumor cell dissemination has, at least in part, been shown for gastric, pancreatic and colon cancer, and the prognostic data regarding gastric cancer are most convincing. Peritoneal "micrometastases" are obviously not equivalent to distant metastases as the evidence for their prognostic significance is clearly less than that for gross peritoneal metastases. This article gives a critical review of the detection and prognostic significance of disseminated tumor cells in the peritoneum of patients with gastrointestinal cancer.
 ...
PMID:Are "micrometastases" of the peritoneum equivalent to distant metastases? 1249 36

The cure of a tumor patient with gastrointestinal cancer is dependent on the extension of the primary tumor (TNM-classification) and the option of curative resection (R0-resection) at the time of operation. The additional application of multimodal therapy approaches has lead to an improvement of prognosis in different advanced tumor stages. Nevertheless, despite curative tumor resection about 50% of patients with locally advanced gastrointestinal cancer develop recurrent tumor disease or distant metastases and die tumor-related. A possible explanation is the seed of disseminated tumor cells in blood, bone marrow or lymph nodes pre-, intra- or postoperatively, but also during diagnostic procedures. Several studies have shown in the last years that the presence of minimal residual disease (MRD) influences the course of disease and the patient's prognosis after curative tumor resection. Although several groups have reported the prognostic impact of disseminated tumor cells in the different compartments of bone marrow, lymph nodes and blood, the phenomenon of minimal residual disease is not acknowledged as an established prognostic factor and is not integrated into the classification of the UICC. Therefore, no therapeutic consequences were drawn at present from the detection of disseminated tumor cells in patients with gastrointestinal cancer. A possible explanation are missing multi-center-studies, which confirm the results of the several single-center-studies. Standardization of study designs and methodical procedures and the evidence of reproduction are mandatory in order to value and interpret the multitude of studies and the available data in this field. Only these results will allow to decide if the presence and detection of disseminated tumor cells can alter the tumor staging and individualize or possibly minimize further oncological therapy strategies.
 ...
PMID:[Minimal residual disease in gastrointestinal tumors: tumor detection in bone marrow, blood and lymph nodes]. 1250 60

The current status of lymphatic mapping and sentinel node biopsy in patients with selected carcinomas of the digestive tract is described. The possible future use of the method in patients with gastric, small bowel and colorectal malignancies is considered. Preoperative lymphatic mapping and reliable identification of sentinel node (nodes) in patients with gastrointestinal cancers may lead to tailored resections or limited surgical procedures. On the other hand, extended lymph node dissection may be performed in those patients in whom the sentinel node(s) contains tumour cells or in cases where skip lymphatic nodes metastases appear. The method offers the opportunity of improving staging (ultrastaging) by identification of patients with early dissemination in lymphatic nodes where conventional methods are not sensitive enough. These patients should be considered for traditional adjuvant treatment or be included in trials with more effective adjuvants regimens. Large prospective multicenter studies are needed to find out if the sentinel node concept is valid in gastrointestinal cancer. If the answer is yes, several basic diagnostic and therapeutic measures may be changed in favour of cancer patients.
 ...
PMID:[Lymphatic mapping and sentinel lymph node biopsy in selected carcinomas of the digestive tract]. 1251 1

Colorectal Cancer (CRC) is the most frequent digestive cancer in France and a major public health problem. The benefits of adjuvant chemotherapy after curative resection of Stage III CRC has been clearly demonstrated. For metastatic CRC, palliative chemotherapy allows an improvement in survival duration and quality of life compared with symptomatic treatment. 5-FU/Leucovorin chemotherapy (Mayo Clinic protocol and LV5FU2) is the standard adjuvant therapy. The addition of irinotecan (FOLFIRI) or oxyplatin (FOLFOX) to this regimen may improve response in palliative situations. These two regimens have shown their superiority to 5FU/Leucovorin in both tumor response and survival. A good objective response to palliative chemotherapy may allow for a secondary resection of hepatic metastases as part of a multidisciplinary approach. Current studies aim to define: 1) optimal treatment strategies (which drug protocols? in what order?) as they apply to tumor spread, drug toxicity profiles, the general state of the patient, and the desired therapeutic effect; 2) evaluation of new drugs and novel therapeutic approaches. Despite notable progress, the prognosis still remains grim with a survival of only 40% at 5 years. Any improvement in results will require not only an improvement in chemotherapy but also an improvement in methods of early diagnosis (systematic mass screening) which would permit the diagnosis of CRC at earlier stages where curative resection is feasible.
 ...
PMID:[Chemotherapy for colorectal cancers]. 1270 55

Chemosensitivity testing is considered by some to be a useful method for predicting drug sensitivity of tumor tissues after surgery for gastrointestinal cancer. Although survival benefit is not fully established, several chemosensitivity testing methods have been used clinically, both in the selection of adjuvant therapy and in the treatment of metastatic disease. Chemosensitivity testing is used not only for determination of drug resistance, but also for determination of drug sensitivity conferring a potential survival benefit. Previous retrospective correlation studies showed survival of patients treated with a 'tested' drug to be superior to that of patients treated with a standard drug, but the clinical benefit of chemosensitivity testing in comparison to surgical therapy alone or standard chemotherapy has not been documented in a randomized controlled trial. The clinical usefulness of individualized versus standard therapy needs to be determined. Here we discuss the potential survival benefit and current limitations of chemosensitivity testing in patients with gastrointestinal cancer.
 ...
PMID:Chemosensitivity testing for gastrointestinal cancer: survival benefit potential and limitations. 1455 4

Although peritoneal metastasis is an important factor determining the prognosis of patients with gastrointestinal cancer, the mechanisms have not yet been clearly defined. Human peritoneal mesothelial cells (HPMC) are the first line against disseminated tumor cells. Recent reports have shown that mesothelial cells are capable of secreting various cytokines and growth factors. In this study, we isolated human mesothelial cells from surgically resected omental tissue and examined the production and interaction of two major angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2). Quiescent HPMC produced a considerable amount of VEGF at almost the same level as tumor cells. Interestingly, addition of FGF-2 to the culture significantly increased the mRNA synthesis and protein secretion of VEGF in a dose-dependent manner, as determined by Northern blot and ELISA. The addition of 0.5 ng/mL FGF-2 was enough to stimulate VEGF production, and the effect reached a plateau at 5 ng/mL. Reverse-transcribed polymerase chain reaction (RT-PCR) method clarified that the HPMC-derived VEGF consisted mostly of VEGF(121) and VEGF(165), which are both predominantly soluble forms. These data suggest that HPMC contribute to the development of metastases and the accumulation of malignant ascites due to the production of VEGF, especially in cancers that do not express enough amount of VEGF.
 ...
PMID:Vascular endothelial growth factor synthesis by human omental mesothelial cells is augmented by fibroblast growth factor-2: possible role of mesothelial cell on the development of peritoneal metastasis. 1457 81

The clinical significance of micrometastasis in sentinel nodes (SNs) may differ in various organs. In particular, the prognostic value of SN micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) is still controversial. We investigated the diagnostic and therapeutic significance of nodal molecular metastasis detected by nested RT-PCR for cytokeratin (CK) 19 mRNA in gastrointestinal cancer. In 51 cases with GI tract cancer treated by standard curative resection, SNs were identified by a radio-guided method. In 10 of 51 patients, 25 SNs and 3 non-SNs were histologically negative and RT-PCR positive. Three non-SNs with positive CK19 mRNA were randomly sampled from the same basin where histologically positive SNs were identified. Immunohistochemical analysis of six additional step sections obtained at 30- micro m intervals with use of an anticytokeratin antibody showed clearly recognizable histological metastases in 4 of 25 histologically negative/RT-PCR-positive SNs (16%). In one case of esophageal squamous cell carcinoma with nodal micrometastasis identified by CK19 RT-PCR, extranodal local recurrence in the SN basin (left supraclavicular basin) was observed 6 months postoperatively. These findings suggest that nodal micrometastasis detected by nested RT-PCR has some clinical significance in GI cancer. Molecular assessment of the SN may be a valuable tool to complement routine histological examination for GI cancers.
 ...
PMID:Significance of metastasis detected by molecular techniques in sentinel nodes of patients with gastrointestinal cancer. 1502 62

Colorectal cancer is leading digestive cancer in western countries and United States and second fatal malignance, after lung cancer. 190,000 people die from colonic cancer in Europe every year. By the time of diagnosis, 25% patients are presented with metastases. Overall surveilance is low, 20-25%. That number is influenced by disease extension in the time of diagnosis, comorbidity, age of patient. The worst prognosis is in patients with diseases presented with urgent complications (bowel perforation or bowel obstruction). Colonoscopy is method of greatest potential in decreasing the mortality of colorectal cancer.
 ...
PMID:[Carcinoma of the anus, rectum and colon]. 1513 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>