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PubMed2002

[Effectiveness of continuous hyperthermic peritoneal perfusion for the peritoneal dissemination of gastric cancer].

We investigated the effectiveness of continuous hyperthermic peritoneal perfusion (CHPP) for the peritoneal dissemination of gastric cancer. A total 124 patients with advanced gastric cancer were enrolled in this study. Prophylactic CHPP (P-CHPP) was performed in 45 patients who had macroscopic serosal invasion without peritoneal dissemination, and 79 patients without CHPP were a control group. Therapeutic CHPP (T-CHPP) was performed in 21 patients with peritoneal dissemination, and 52 patients without CHPP were a control group. There was no significant difference in 5 year survival between patients treated and not treated with P-CHPP. Univariate analysis showed that location of tumor, tumor diameter, and lymph node metastasis influenced prognosis, but there was no prognostic factor in the Cox proportional regression hazard model. There was no significant difference in 5-year survival between patients treated and not treated with T-CHPP. Univariate analysis showed that degree of peritoneal dissemination and adjuvant chemotherapy influenced prognosis, and the Cox proportional regression hazard model showed that the macroscopic types and degree of peritoneal dissemination affected prognosis. In the patients with CHPP, the incidences of respiratory failure and renal failure were each statistically greater than in the patients undergoing CHPP.

Aged↗

PubMed2002

[Detection, quantification and characterization of disseminated tumor cells].

There are different reasons why the detection of disseminated tumor cells (DTCs) in the hematopoetic system is important. On the one hand the detection of disseminated tumor cells can provide vital information about a tumor's tendency to develop metastases. In some localized epithelial but also in embryonic tumors, for example a correlation between disseminated tumor cells and unfavorable outcome was observed (6, 14). These studies are based on the assumption that those tumor cells which appear in the hematopoetic system at a very early stage are responsible for the development of metastases. Another important aspect is the monitoring of the disease response to cytotoxic drugs by quantifying DTCs. During and after therapy there is no other possibility (except for an operation) to either directly analyze the effects the therapy has on the tumor cells or to determine their biological characteristics. The dissemination in the hematopoetic system, however, reveals the response to therapy and the biological features of the tumor cells. The prerequisites for such bone-marrow diagnosis, however, is the unequivocal identification of disseminated tumor cells. So in order to avoid false positive results (which are a risk in bone-marrow diagnostics), a system was developed to distinguish tumor cells from non-neoplastic cells and to facilitate insights into the biological make-up of tumor cells (2, 11).

Antineoplastic Agents↗

PubMed2003

Patients with localized and disseminated tumors have reduced but measurable levels of ADAMTS-13 (von Willebrand factor cleaving protease).

BACKGROUND AND OBJECTIVES: Patients with disseminated malignancies have been noted to have a deficiency of von Willebrand factor (VWF) cleaving protease, ADAMTS-13. The very low or undetectable plasma levels of this protease are said to be similar to those found in patients with thrombotic thrombocytopenic purpura (TTP). This observation, which challenges the paradigm that severe ADAMTS-13 deficiency is a specific diagnostic marker for TTP, remains so far unconfirmed. DESIGN AND METHODS: We measured the protease and VWF antigen (VWF:Ag) in parallel in 49 Iranian patients with solid tumors, which in 29 cases were localized (stages I and II) and in 20 disseminated (stage IV). Forty-nine healthy individuals matched with cases for sex, age and smoking habits were taken as controls. RESULTS: Patients with disseminated tumors had lower mean plasma levels of ADAMTS-13 than those with localized tumors, but these differences did not reach the level of statistical significance (p=0.059). However, in no patient was the level of ADAMTS-13 below 18% of normal, at variance with previous findings of lower or unmeasurable levels (<15%). The level of ADAMTS-13 was significantly lower in patients with localized tumors than in controls ( p = 0.0003 ), but higher than in patients with disseminated disease (p=0.0001 vs controls). INTERPRETATION AND CONCLUSIONS: Malignancy, whether localized or disseminated, is another condition associated with low ADAMTS-13 levels not accompanied by signs and symptoms of TTP and other thrombotic microangiopathies.

ADAM Proteins↗

PubMed2003

Diffuse ulcerations due to disseminated histoplasmosis in a patient with HIV.

Disseminated histoplasmosis is a serious disease that affects the skin, lungs, and internal organs. It is one of the diseases that characterize acquired immunodeficiency syndrome (AIDS), and in endemic areas is one of the more commonly observed infections in AIDS patients. The mortality rate in patients with AIDS and histoplasmosis is high if untreated. Disseminated histoplasmosis may have a variety of dermatological manifestations. In this article, we provide the first report of diffuse ulcerations due to disseminated histoplasmosis. These ulcers developed while the patient was on stavudine, lamivudine, and indinavir, and had a CD-4 count of 525 mm3. The patient's histoplasmosis resolved with itraconazole monotherapy. Histoplasmosis is a well-described opportunistic infection that accompanies human-immunodeficiency virus (HIV) infection. We report an unlikely victim of disseminated histoplasmosis who suffered this infection while on antiretroviral therapy and with a CD-4 count of 525/mm3. Notably, he had a normal chest x-ray and disseminated cutaneous ulcers. The diagnosis was made by skin biopsy, and his infection responded promptly to itraconazole therapy. This case serves as a reminder that the immunological derangements and cutaneous alterations wrought by HIV remain unpredictable in nature and extent.

Adult↗

PubMed2003

Magnetic resonance imaging of meningoradiculomyelitis in early disseminated Lyme disease.

Lyme disease, a multisystem illness caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. There are 3 clinical stages of Lyme disease: early localized, early disseminated, and late persistent disease. Neuroborreliosis, infection of the nervous system by B. burgdorferi, may occur during early disseminated or late persistent disease. Spinal cord involvement in early disseminated disease is extremely rare. In patients with early disseminated neuroborreliosis, treatment with antibiotics often leads to rapid recovery and may prevent further complications of Lyme disease. The authors present the clinical and radiographic findings, both before and after treatment, in a patient with meningoradiculomyelitis due to early disseminated Lyme disease.

Adult↗

PubMed2003

Prolonged dormancy and site-specific growth potential of cancer cells spontaneously disseminated from nonmetastatic breast tumors as revealed by labeling with green fluorescent protein.

This study used an isogenic pair of metastatic (M4A4) and nonmetastatic (NM2C5), green fluorescent protein-labeled human breast cancer cell lines derived from the same patient and inoculated into the mammary glands of nude mice to investigate the dissemination patterns and fate of cells that escaped spontaneously from the resulting tumors. After tumors appeared, fluorescing single tumor cells were regularly seen in the lungs, even in animals inoculated with NM2C5, which fails to form secondary tumors in other organs. The sensitivity of the technique confirmed the continuing presence of scattered NM2C5 cells after primary tumor resection, although they formed no metastases by 6 months. These self-disseminated human tumor cells were retrievable from the tissues and were still viable and malignant, manifested by indefinite proliferation in vitro and green fluorescence and local tumorigenicity in vivo. Therefore, these scattered tumor cells were still immortal but rendered indefinitely quiescent by the microenvironmental conditions in the lung tissue. This is the first unequivocal demonstration of spontaneous distant dissemination of human cancer cells by undisturbed nonmetastatic tumors and comprises a valuable system for the analysis of tumor dormancy. In contrast, although many of the cells disseminating from M4A4 tumors grew into fluorescing metastases in the lungs, others remained solitary and quiescent. Therefore, even in a clonally derived cell population with metastatic properties, many cells do not, or cannot, mobilize the organ-specific growth properties needed to generate metastases. This experimental approach, by using self-disseminating, green fluorescent protein-labeled, sister cell lines of opposing metastatic phenotypes, opens new avenues for investigating topics of clinical relevance, including tumor cell dormancy, anatomical distribution of metastases, and host factors influencing the metastatic process.

Animals↗

PubMed2003

[Possible involvement of inositol 1, 4, 5-trisphosphate receptor type 3 (IP3R3) in the peritoneal dissemination of gastric cancers].

Our previous study using a cDNA microarray demonstrated that positive identification of differently expressed genes among gastric cancer cells involved in peritoneal dissemination could be accomplished. One of these genes with overexpression is inositol 1, 4, 5-trisphosphate receptor type 3 (IP3R3). IP3R3 is an intracellular Ca2+ release channel responsible for mobilizing stored Ca2+. Three different receptor types have been molecularly cloned, and their genes have been classified into a family. But the role of the IP3 signaling pathway in the peritoneal dissemination of gastric cancers is still unclear. In this study, IP3R3 is overexpressed in gastric cancer cell lines established from malignant ascites, but weakly expressed in gastric cancer cell lines established from primary tumor as well as in normal gastric epithelial cells. IP3R1 and 2 are expressed only weakly or not at all in these cells. The antagonist of IP3R, 2-APB, inhibited cell proliferation and induced apoptosis of gastric cancer cells from malignant ascites at concentrations of 100 nM to 100 microM in a dose dependent manner. Conversely, 2-APB showed a weak effect on other gastric cancer cells established from primary tumors (SNU1), lymph node metastases or liver metastases (MKN1 or 74), methothelial cell lines Met5A and myeloid leukemia cell HL60 cells. This suggests that this inhibitory effect depends on the level of IP3R3 expression. As cells that express IP3R3 mRNA (i.e., pancreatic aciner cells) are known to have a secretory function in which IP3/Ca2+ signaling has been shown to be involved, IP3R3 may be a prerequisite for secretion in gastric cancer cells. These results indicate that IP3R3 may be specifically involved in gastric cancer peritoneal dissemination and that IP3R3 may be a molecular target of the peritoneal dissemination of gastric cancer. Its antagonist, 2-APB, may thus be useful for the treatment of gastric cancer, especially for peritoneal dissemination.

Apoptosis↗

PubMedDate not supplied

Possible involvement of inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) in the peritoneal dissemination of gastric cancers.

Our previous study using cDNA microarray showed that differentially expressed genes among gastric cancer cells involved in peritoneal dissemination could be positively identified. One of these genes, which is overexpressed, is inositol 1,4,5-trisphosphate receptor type 3 (IP3R3). IP3R3 is responsible for the intracellular Ca2+ release channel and for mobilizing stored Ca2+. Three different receptor types have been molecularly cloned and their genes have been classified into a family. However, the role of the IP3 signaling pathway in the peritoneal dissemination of gastric cancer is still unclear. In the study presented here, the IP3R3 is showed to be overexpressed in gastric cancer cell lines established from malignant ascites, but weakly expressed in a gastric cancer cell line established from primary tumor as well as normal gastric epithelial cells. IP3R1 and 2 are only weakly or not expressed in these cells. The antagonist of IP3R, 2APB, inhibited cell proliferation and induced apoptosis in gastric cancer cells from malignant ascites at concentrations of 100 nM to 100 microM in a dose-dependent manner. On the other hand, 2APB showed a weak effect on other gastric cancer cells established from primary tumors (SNU1), lymph node metastases or liver metastases (MKN1 or 74), methothelial cell lines Met5A and myeloid leukemia HL60 cells. This suggests that this inhibitory effect depends on the level of IP3R3 expression. As cells which express IP3R3 mRNA (i.e. pancreas ascinar cells) are known to have a secretory function in which IP3/Ca2+ signaling has been shown to be involved, IP3R3 may be a prerequisite for secretion of an enzyme, such as protease, in gastric cancer cells. These results indicate that IP3R3 may be specifically involved in gastric cancer peritoneal dissemination and that IP3R3 may be a molecular target of the peritoneal dissemination of gastric cancer. Its antagonist, 2APB, may thus be useful for the specific treatment of peritoneal dissemination of gastric cancer.

Apoptosis↗

PubMed2003

[Two resected cases of advanced gastric cancer with peritoneal dissemination after successful treatment with TS-1 plus low-dose CDDP].

We report two resected cases of advanced gastric cancer with peritoneal dissemination after successful treatment with TS-1 plus low-dose CDDP. Patient 1 presented with right hypochondralgia and underwent laparotomy with diagnosis of type 4 gastric cancer by gastrointestinal fiberscopy. However, the tumor was judged to be unresectable due to peritoneal dissemination, and chemotherapy was performed. At the completion of course 1, he underwent laparotomy again. Although the tumor involved the body of the pancreas and transverse colon, there was no peritoneal dissemination. Therefore, a total gastrectomy was performed with distal pancreatectomy, partial colectomy, cholecystectomy, and D2 lymph node dissection. Patient 2 presented with anorexia and was diagnosed with type 3 gastric cancer by gastrointestinal fiberscopy. CT revealed the tumor was unresectable due to peritoneal dissemination, and so chemotherapy was performed. He underwent laparotomy at the completion of course 3. There was no peritoneal dissemination, so a total gastrectomy was performed with cholecystectomy and D2 lymph node dissection. Both patients remain alive and in good condition without any signs of recurrence after surgery.

Aged↗

PubMed2004

[Over expression of Reg IV in peritoneal dissemination of gastric cancer].

We previously performed a global analysis of the gene expression of gastric cancer cell lines established from peritoneal dissemination (SNU-5, SNU-16, SNU-719, KATO-III and GT3TKB) with the cDNA microarray method to identify the novel markers for the detection of micro-metastasis in peritoneal cavity. One of the up-regulated genes is Reg IV, which is a member of the Reg gene family belonging to calcium dependent lectin (C-type lectin) gene superfamily. We have examined Reg IV potential as a novel marker for the detection of peritoneal micro-metastases of gastric cancer. Reg IV expression was examined in five gastric cancer cell lines established from peritoneal dissemination and compared with myeloid leukemia cell (HL60), methothelial cell lines Met5A and the other gastric cell line established from primary tumor (SNU-1) by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Reg IV was highly overexpressed in 4 gastric cancer cell lines established from peritoneal dissemination, but weakly expressed in other cell lines. According to Reg IV mRNA expression levels in surgically resected specimens, the quantity of Reg IV correlated with wall penetration. Furthermore, Reg IV mRNA expression level in the peritoneal wash from 35 gastric cancer patients was also prone to correlation with wall penetration. These results suggest that Reg IV may be involved in peritoneal dissemination of gastric cancers and Reg IV may be a potential novel marker for peritoneal dissemination of gastric cancers.

Biomarkers, Tumor↗

PubMedDate not supplied

Influence of tumor biological factors on tumor cell dissemination in primary breast cancer.

BACKGROUND: The presence of disseminated tumor cells in the bone marrow (BM) of breast cancer patients is associated with poor prognosis and may therefore be related to aggressive breast cancer as indicated by tumor biological and clinicopathological factors. The aim of this study was to identify those features of the primary tumor related to the presence of disseminated tumor cells in the BM. PATIENTS AND METHODS: Clinical data from 508 primary breast cancer patients were analyzed. Tumor biological features of the primary tumor including HER2, p53, Ki-67, bcl-2 and hormone receptor status, as well as clinicopathological factors including histology, menopausal status, lymph node status, tumor size and grade, were studied for their association with BM involvement by univariate and multivariate analysis. RESULTS: Two-hundred and two out of 508 (40%) primary breast cancer patients had disseminated tumor cells in the BM. p53 expression, hormone receptor status, HER2 and Ki-67 were significantly related to BM involvement. The multivariate analysis revealed that p53 expression (OR: 1.9, 95% CI: 1.2 - 3.0) followed by progesterone receptor status (OR: 1.5, 95% CI: 1.0 - 2.2) were the only independent determinants for BM involvement. CONCLUSION: The presence of disseminated tumor cells in the BM was not influenced by tumor load as reflected by tumor size and lymph node involvement, whereas tumor biological factors were independently correlated to BM involvement. The results substantiate the important role of tumor biological factors of the primary tumor for tumor cell dissemination.

Bone Marrow↗

PubMedDate not supplied

Tyrosine kinase inhibitor SU6668 inhibits peritoneal dissemination of gastric cancer via suppression of tumor angiogenesis.

BACKGROUND: Peritoneal dissemination of cancer involves several steps, including tumor cell attachment, invasion and growth in the peritoneum. Tumor angiogenesis is a prerequisite for the growth of disseminated tumor. Vascular endothelial growth factor (VEGF) and its receptor are major regulators of angiogenesis. PURPOSE: We examined the cytotoxic effects of SU6668, an inhibitor of VEGF tyrosine kinase receptors, on in vitro gastric cancer cell lines and human umbilical vascular endothelial cells (HUVEC); we also examined the antitumor effects of SU6668 on human gastric cancer cells administered intraperitoneally into nude mice. MATERIALS AND METHODS: Direct cytotoxicity to gastric cancer cells (TMK-1, MKN-45 and MKN-74) and normal cells (HUVEC) was determined by the MTT assay and the bromodeoxyuridine (BrdU) incorporation assay, with and without VEGF-evoked growth stimulation in vitro. TMK-1 cells were transplanted intraperitoneally into nude mice, followed by twice daily oral administration of SU6668 (200 mg/kg/day) for two weeks starting on the first day after transplantation. Both the number and the wet weight of disseminated peritoneal tumor nodules were assessed. RESULTS: In the MTT assay, SU6668 demonstrated low-grade cytotoxicity to the cell growth of three gastric cancer cells, with a 50% inhibitory concentration (IC50) of 22.6 microg/ml for TMK-1, 31.8 microg/ml for MKN-45 and 26.7 microg/ml for MKN-74; HUVEC was sensitive to SU6668 with an IC50 of 8.9 microg/ml. In the BrdU assay, VEGF stimulated DNA synthesis in HUVEC, while the incorporation of BrdU was not affected by VEGF in gastric cancer cell lines. SU6668 inhibited VEGF-induced DNA synthesis in HUVEC, while BrdU incorporation of gastric cancer cell lines was inhibited by SU6668 without correlation to VEGF stimulation. Peritoneal dissemination of cancer in nude mice was significantly suppressed by SU6668 compared with a control group at the p<0.05 level. CONCLUSION: The mechanism of the antitumor activity of SU6668 may not involve direct toxicity to cancer cells, but may rather be an inhibitory effect on tumor angiogenesis, resulting in the inhibition of tumor dissemination in the peritoneum.

Adult↗

PubMed2005

[A rare case of disseminated Mycobacterium kansasii infection].

Mycobacterium kansasii infection has been reported to be about 20 percent of non-tuberculous mycobacteriosis, and its disseminated type is uncommon and the prognosis is reported to be generally poor. We experienced one case of disseminated Mycobacterium kansasii infection. A 81 year-old man who had been short-bowel syndrome due to the operation for superior mesenteric artery occlusion since 1998 was admitted on April 24th, 2001 to our hospital because of slowly progressive consciousness disturbance and anorexia. He had shown progressive productive cough and respiratory failure and laboratory findings were C-reactive protein elevation and pancytopenia. Human immunodeficiency virus (HIV) antibody was negative. Chest X-ray and computed tomography showed diffuse miliary nodules and infiltrative shadow. Sputum examination was positive for mycobacteria. The cultured isolate was identified as Mycobacterium kansasii. Bone marrow aspirations revealed inflammatory granuloma with necrosis. He was diagnosed as disseminated Mycobacterium kansasii infection and heart failure, and was treated by anti-tuberculosis drugs and diuretics. Treatment was very effective and Chest X-ray findings and respiratory failure had been completely improved. In this case we speculated that the malnutrition due to short-bowel syndrome could be one of the most suspected reasons of Mycobacterium kansasii dissemination. Disseminated Mycobacterium kansasii infection has been rarely reported comparing with the other mycobacterial infections in Japan. However, due to the increasing numbers of immunocompromised hosts with aging, HIV infection, cancer, and steroid therapy, this type of infection will become more common and its earlier diagnosis and adequate treatment will be important to improve the prognosis.

Aged↗

PubMed2006

HRCT shows variations in appearance in disseminated tuberculosis in adults.

OBJECTIVE: To examine patterns of high resolution computed tomography (HRCT) of lungs of adults with disseminated tuberculosis (TB). DESIGN: Disseminated TB was defined as radiological involvement of all lung lobes. RESULTS: The case series illustrated wide variation in HRCT of disseminated TB. Patterns identified on HRCT included (1) miliary TB (haematogenous dissemination), (2) miliary TB with exudative reaction, (3) bronchogenic spread, (4) miliary TB mixed with bronchogenic spread, and (5) bronchogenic spread with multiple cavity formation. CONCLUSION: The HRCT patterns described allow classification of disseminated TB according to the mechanism of spread (haematogenous and/or bronchogenic) and the degree of local lung involvement (reaction or cavitation).

Aged↗

PubMed2003

[From single disseminated tumor cells to metastasis insights from molecular genetic analyses of single cells].

The prevailing models of cancer metastasis postulate that, after a series of accumulating genetic and epigenetic changes during transformation and invasive growth, the most advanced clone within a primary tumour acquires the critical cellular phenotype enabling dissemination and metastasis. This postulate is particularly based on observations that metastases usually display more genetic changes than the primary tumour. The development of several novel techniques is now enabling experimental testing of the model: The detection of single disseminated cancer cells by epithelial specific antibodies directed against cytokeratin in mesenchymal tissues has become possible even before manifestation of metastasis. After their isolation by micromanipulation comprehensive amplification of the single cell genomes allows the application of several molecular genetic methods for further characterisation. Our first data from single cytokeratin-positive cells that were isolated from the bone marrow of breast cancer patients indicate that the model of cancer progression should be revised. Cancer cells already disseminate in an early stage of genomic development and still have to acquire the critical chromosomal aberrations needed for metastatic outgrowth and full malignant potential. These observations apparently imply consequences for the development of novel adjuvant therapies. The early diversification of primary tumours and disseminated cancer cells precludes a simple extrapolation from local to systemic disease eventually necessitating increasing efforts for the direct analysis of single disseminated cancer cells as the cellular targets of adjuvant therapies.

Bone Marrow↗

PubMed2006

[X-ray features of disseminated pulmonary tuberculosis at late stages of HIV infection].

The paper analyzes the results of a study of X-ray features of disseminated pulmonary tuberculosis in HIV infection on the basis of a retrospective analysis of the case histories of 65 HIV-infected patients with disseminated pulmonary tuberculosis and 60 patients with disseminated tuberculosis without HIV infection, who have been followed up in the Krasnodar Territory. X-ray changes characteristic for patients with disseminated tuberculosis in HIV infection and their difference from those with disseminated tuberculosis without HIV infection have been ascertained, which assists in timely establishing the diagnosis of tuberculosis in HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed2006

[A case of advanced gastric cancer with peritoneal dissemination responding remarkably to TS-1/CDDP combination chemotherapy].

A 57-year-old woman visited a physician with complaints of anorexia and pollakiuria. Because a pelvic tumor and ascites were detected, she was referred to our department. Douglas pouch puncture revealed adenocarcinoma cells. Further examination showed an advanced gastric cancer with peritoneal dissemination. The cancer was judged to be unresectable. Chemotherapy with a combination of TS-1 and CDDP was performed before the operation. After 2 courses of the chemotherapy, her complaints disappeared, although abdominal CT confirmed remaining peritoneal dissemination. After 7 courses of chemotherapy, abdominal CT showed that the peritoneal dissemination had disappeared. Total gastrectomy and lymph node dissection were performed. Histological findings of the stomach revealed complete disappearance of cancer cells in the stomach and the regional lymph nodes. We confirmed that the TS-1/CDDP therapy resulted in a complete response to advanced gastric cancer and peritoneal dissemination. We recommend that chemotherapy be continued until the peritoneal dissemination disappears.

Adenocarcinoma↗

PubMed1991

[Differential diagnosis of disseminated processes in the lungs in adolescents].

The paper deals with the data of follow-up of adolescents with disseminated pulmonary processes of different etiology. Among the patients who were treated in the department during the last 10 years disseminated processes amounted to 3.3%, with disseminated pulmonary tuberculosis being recorded in 1.3% and dissemination of the nontuberculous etiology in 2% of the patients. Mucoviscidosis, metastasis, of the thyroid cancer, histiocytosis X, toxoplasmosis and echinococcosis were among the disseminations of the nontuberculous etiology. Basic diagnostic criteria have been determined.

Adolescent↗