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PubMed1975

Disseminated gonococcal infections caused by Neisseria gonorrhoeae with unique nutritional requirements.

Disseminated gonococcal infection occurs in 1%-3% of patients with gonorrhea in Seattle. Most strains of Neisseria gonorrhoeae recovered from patients with disseminated gonococcal infection are susceptible to less than or equal to 0.015 mug of penicillin G/ml. Strains susceptible to less than or equal to 0.015 mug/ml, whether isolated from patients with disseminated gonococcal infection or from those with uncomplicated infection, did not grow on chemically defined medium prepared with several lots of agar, whereas less susceptible isolates grew well. Use of methanol-extracted nontoxic agar permitted growth of the penicillin-susceptible strains and demonstrated that all of them required arginine, hypoxanthine, and uracil (Arg-Hyx-Ura-) for growth. These Arg-Hyx-Ura- strains accounted for 89% of the cases of disseminated gonococcal infection in Seattle, 38% of uncomplicated infections in Seattle, 18% of infections in Milwaukee, and none of 104 uncomplicated gonococcal infections acquired in the Philippines and Taiwan, where disseminated gonococcal infection is unusual. Regional variations in the prevalence of these Arg-Hyx-Ura- strains may correlate with regional variations in the incidence of disseminated gonococcal infection. The genetic, physiologic, and immunologic bases for concurrence of penicillin and agar susceptibility. Arg-Hyx-Ura- phenotype, and association with disseminated gonococcal infection remain undefined, as do host factors that determine whether or not disseminated gonococcal infection will result in patients infected by such strains.

Adult↗

PubMed1990

Effects of preventive, early, and late antifungal chemotherapy with fluconazole in different granulocytopenic models of experimental disseminated candidiasis.

To investigate the potential use of fluconazole for prevention and treatment of disseminated candidiasis in granulocytopenic patients, its in vivo antifungal activity was studied in three models of disseminated candidiasis in persistently granulocytopenic rabbits: acute, subacute, and chronic disseminated candidiasis. Fluconazole was compared with the combination of amphotericin B and flucytosine for preventive, early, and late treatment of disseminated candidiasis, depending on the model. Fluconazole was most effective when used for preventive or early treatment of acute and subacute disseminated candidiasis. When compared with the combination of amphotericin B plus flucytosine, fluconazole was similarly effective in early treatment of acute and subacute disseminated candidiasis. When treatment was delayed 6 days after established infection, fluconazole was less active in clearing tissues in comparison with its activity in preventive and early treatment. The combination of amphotericin B plus flucytosine, however, was significantly more active than fluconazole in treatment of chronic disseminated candidiasis in all tissues. In summary, fluconazole was most effective against disseminated candidiasis in persistently granulocytopenic rabbits when used for prevention or early treatment.

Acute Disease↗

PubMed1997

Disseminated Mycobacterium avium complex disease in the Swiss HIV Cohort Study: increasing incidence, unchanged prognosis.

OBJECTIVES: Disseminated disease due to Mycobacterium avium complex (MAC) bacteria is thought to occur less frequently in Europe than in the USA. This study investigated time trends in the occurrence of, and survival with, disseminated MAC disease in the Swiss HIV Cohort Study (SHCS). DESIGN, SETTING AND PARTICIPANTS: The SHCS participants who were free of disseminated MAC disease at registration were stratified by calendar period (1987-1989, 1990-1992, 1993-1995) in which the first recorded CD4 count was 0-49, 50-99, or 100-199 x 10(6)/l. Kaplan-Meier estimates of the probability of developing and surviving disseminated MAC disease were calculated for these nine independent groups. Multivariate analyses were performed using Cox proportional hazards regression. RESULTS: The analysis was based on 6052 participants enrolled between January 1987 and December 1995 and 202 incident episodes of disseminated MAC disease recorded during a mean follow-up time of 3.5 years. The cumulative probability of MAC disease at 2 years in individuals with CD4 counts of 0-49 x 10(6)/l in 1987-1989 was 9.8% [95% confidence interval (CI) 4.4-15.2%], increasing to 29.8% (95% CI, 20.8-38.8%) in 1993-1995. Amongst those with CD4 counts from 50-99 x 10(6)/l these probabilities were 11.9% (95% CI, 5.9-17.8%), and 21.6% (95% CI, 13.9-29.2%), respectively. After adjusting for CD4 count the relative hazard of developing disseminated MAC disease in 1993-1995, compared with 1987-1989, was 1.37 (95% CI, 0.92-2.04). Median survival following diagnosis was 7.9 months with no improvement over time. CONCLUSIONS: The incidence of disseminated MAC disease among SHCS participants has increased over time. More profound levels of immunosuppression amongst recent study entrants were found to explain this. When compared with US cohorts studied over the same calendar period the incidence of disseminated MAC disease in the SHCS appears to be lower. These findings are consistent with a secular effect of a more mature HIV epidemic in the US but direct comparison between the SHCS and a similar prospective cohort in the US should be undertaken to clarify this issue.

AIDS-Related Opportunistic Infections↗

PubMed2007

Recent advances in the treatment of peritoneal dissemination of gastrointestinal cancers by nucleoside antimetabolites.

Peritoneal dissemination is the most common cause of metastasis from malignancies in the abdominal cavity. There are no standard treatments for peritoneal dissemination and the results are poor. The reasons for this are as follows: (1) no effective chemotherapeutic agents have been identified or developed; (2) surgical cytoreduction has little effect on survival improvement; and (3) the molecular mechanisms of peritoneal dissemination have not been clarified and no therapy against the target molecules has been developed. However, studies on the molecular mechanisms of peritoneal dissemination have elucidated some of the target molecules and the development of new multimodal therapies has also improved survival. Early postoperative intraperitoneal chemotherapy, hyperthermic intraperitoneal perfusion chemotherapy and neoadjuvant intraperitoneal-systemic chemotherapy have been newly developed, and a novel surgical therapy named peritonectomy has been proposed to perform complete cytoreduction of peritoneal dissemination. At present, these approaches appear to be effective therapeutic modalities for peritoneal dissemination. However, TS-1 and capecitabine have shown worthwhile results in recent clinical trials for patients with advanced gastric cancer. We recently found that newly developed antitumor cytosine nucleoside analogs show a survival advantage in peritoneal dissemination models using human cancer cells. These non-fluoropyrimidine nucleosides may potentially help to improve the poor prognosis observed in patients with advanced cancers involving peritoneal dissemination.

Adenocarcinoma↗

PubMed2006

A group randomised trial of two methods for disseminating a smoking cessation programme to public antenatal clinics: effects on patient outcomes.

OBJECTIVE: To assess the differential effectiveness of two methods of disseminating a smoking cessation programme to public hospital antenatal clinics. DESIGN: Group randomised trial. SETTING: 22 antenatal clinics in New South Wales, Australia. INTERVENTION: Clinics were allocated to a simple dissemination (SD) condition (11 clinics) which received a mail-out of programme resources or to an intensive dissemination (ID) condition (11 clinics) which included the mail-out plus feedback, training, and ongoing support with midwife facilitator. MAIN OUTCOME MEASURES: Independent cross sectional surveys of women on a second or subsequent visit undertaken pre-dissemination and 18 months after dissemination. Outcomes were: (1) levels of smoking status assessment by clinic staff; (2) proportion of women identifying as having been smokers at their first visit who reported receiving cessation advice; (3) proportion of these women who had quit (self report and expired air carbon monoxide (CO)); and (4) smoking prevalence among all women (self report and CO). SUBJECTS: 5849 women pre-dissemination (2374 SD, 3475 ID) and weighted sample of 5145 women post-dissemination (2302 SD, 2843 ID). RESULTS: There were no significant differences between the groups on change on any outcome. Change in either group was minimal. In the post-dissemination survey, the cessation proportions were 6.4% (SD) and 10.5% (ID). CONCLUSIONS: Relatively modest strategies for encouraging incorporation of smoking cessation activities into antenatal care were not effective in the long term. Alternative strategies should be implemented and evaluated. The findings reinforce the importance of a whole population approach to tobacco control.

Adolescent↗

PubMedDate not supplied

A new approach to phenotyping disseminated tumor cells: methodological advances and clinical implications.

At the time of primary therapy (surgery, systemic chemotherapy and/or radiation), disseminated tumor cells in the bone marrow can be found in almost one-third of patients with cancer of the breast, ovary, esophagus, stomach, colon, and other solid tumors. Whereas the prognostic impact of the mere presence of these cells is still a matter of debate, it has been shown that expression of tumor-associated antigens in disseminated tumor cells is linked to more aggressive disease. Therefore, further characterization of disseminated tumor cells at the protein and gene level has become increasingly important. To date, the most common detection method for disseminated tumor cells in the bone marrow is an immunocytochemical approach using cytokeratin-directed antibodies for detection of epithelial cells and the APAAP system for their visualization. We have established a new double immunofluorescence technique enabling simultaneous detection, phenotyping, and antigen quantification of disseminated tumor cells. Mononuclear cells from bone marrow are enriched by Ficoll gradient centrifugation and cytospins are prepared. Double immunofluorescence is performed using antibodies against cytokeratins 8/18/19 (mAb A45B/B3) and the uPA receptor CD87 (pAb HU277). CD87 expression is recorded by confocal laser scanning microscopy (CLSM) using fluorescence labeled latex beads as the reference; staining intensities of all the scans are then summed and quantified (extended focus). This protocol, originally designed for disseminated tumor cells in bone marrow, can also be applied to disseminated tumor cells in blood, to leukapheresis cells or to cells present in malignant ascites or other malignant effusions. The tumor cells detected may be used for gene and mRNA analyses. Furthermore, disseminated tumor cells also represent interesting targets for clinical studies on patient prognosis or prediction of therapy response as well as for specific tumor-biological therapies.

Biomarkers, Tumor↗

PubMed2005

Epidermal growth factor receptor gene amplification and expression in disseminated pediatric low-grade gliomas.

OBJECT: Pediatric low-grade gliomas (LGGs) are the largest group of central nervous system neoplasms in children. Although these tumors are generally benign, 5 to 10% of patients with pediatric LGGs present with leptomeningeal dissemination. The genetic and biological nature of these tumors is poorly understood. The authors looked for certain molecular abnormalities that may differentiate disseminated gliomas from the other pediatric LGGs. METHODS: Comparative genomic hybridization (CGH) was applied to 18 pediatric LGGs. Six cases featuring disseminated pediatric LGGs were compared with 12 control cases involving nondisseminated pediatric LGGs. Fluorescence in situ hybridization (FISH) analysis and immunohistochemical analysis were used to highlight further specific genetic targets. The CGH revealed multiple chromosomal abnormalities in five of six cases with disseminated gliomas and in six of 12 control cases. No correlation was found between the number of chromosomal abnormalities and dissemination status. Amplification of chromosome 7 was noted in four of six cases with disseminated gliomas as opposed to one of 12 control cases (p = 0.02). The FISH analysis revealed epidermal growth factor receptor (EGFR) amplification in one case negative to chromosome 7 amplification by CGH, raising the amplification cases to five of six (p = 0.0038). Immunohistochemical analysis for EGFR was positive in six of six cases and in two of 12 control cases (p = 0.0015). At the end of a mean follow-up period of 7.2 years, all patients with disseminated gliomas are alive with variable but slow disease progression. CONCLUSIONS: The high rate of EGFR gene amplification and protein expression in disseminated pediatric LGGs is intriguing and may have implications for our understanding of the role of EGFR in glioma genesis. Targeted therapies may be available for these children. Larger-scale studies are needed to establish further these findings.

Central Nervous System Neoplasms↗

PubMed2000

Mucosa-associated lymphoid tissue lymphoma is a disseminated disease in one third of 158 patients analyzed.

Mucosa-associated lymphoid tissue-derived lymphoma (MALT lymphoma) is usually a very indolent lymphoma, described as localized at diagnosis and remaining localized for a prolonged period; dissemination occurs only after a long course of evolution. In our database, out of 158 patients with MALT lymphoma, 54 patients presented with a disseminated disease at diagnosis. Of these 54 patients, 17 patients (30%) presented with multiple involved mucosal sites; 37 patients (70%) presented with 1 involved mucosal site, but in 23 of these patients (44%), dissemination of the disease was due to bone marrow involvement; 12 patients (22%) had multiple lymph node involvement; and 2 patients (4%) had nonmucosal site involvement. No significant difference in clinical characteristics (sex, age, performance status, B symptoms) and biological parameters (hemoglobin [Hb] and lactate dehydrogenase levels) was observed between localized or disseminated MALT-lymphoma patients. Only beta2-microglobulin level was significantly more elevated in disseminated disease patients than in localized disease patients. Complete response after the first treatment was achieved in 74% of the patients, and there was no difference between the 2 groups. With a median follow-up of 4 years, the estimated 5- and 10-year overall survival rates were similar in the 2 groups, 86% and 80%, respectively. The median freedom-from-progression survival was 5.6 years for all patients, surprisingly without any difference between localized and disseminated MALT-lymphoma patients. In conclusion, MALT lymphoma is an indolent disease but presents as a disseminated disease in one-third of the cases at diagnosis. The dissemination does not change the outcome of the patients.

Adult↗

PubMed2005

[Intraperitoneal chemotherapy in gastric cancer patients with peritoneal dissemination].

Peritoneal dissemination is one of the non-curative factors in gastric cancer and colon cancer. Although many treatments have been conducted for peritoneal dissemination, no standard chemotherapy has yet been established. For sometime we had used continuous hyperthermic peritoneal perfusion (CHPP)for peritoneal dissemination in gastric cancer and colon cancer. CHPP has a marked survival benefit for scirrhous type gastric cancer patients without liver metastasis. Patients with prophylactic CHPP have significantly better prognoses than those without prophylactic CHPP, and therapeutic CHPP has a survival benefit for gastric cancer patients with slight to moderate peritoneal dissemination (P 1-2). But CHPP has no significant prognostic benefit for gastric cancer patients with severe peritoneal dissemination (P 3). Therefore, a new cancer treatment is needed for those patients. On the other hand, many kinds of anticancer agents, including cisplatin, via intraperitoneal (ip) administration have been tried thus far for peritoneal dissemination therapy. Especially, intraperitoneal taxane anticancer agent is very effective for the treatment and local control of severe peritoneal dissemination in gastric cancer. A phase I/II study of taxane anticancer agents via ip administration should be tried in gastric cancer patients with peritoneal dissemination.

Adenocarcinoma, Scirrhous↗

PubMed2006

Manipulation of the yellow fever virus non-structural genes 2A and 4B and the 3'non-coding region to evaluate genetic determinants of viral dissemination from the Aedes aegypti midgut.

Although much is known about the ecology, epidemiology, and molecular biology of mosquito-borne viruses, the viral factors that allow transmission by mosquitoes to humans or animals remain unknown. Using infectious clones of disseminating (Asibi) and non-disseminating (17D) yellow fever viruses (YFV), we produced chimeric viruses to evaluate the role of different viral genes in dissemination. Previously, we showed that virus produced from an infectious clone containing the structural genes of 17D in Asibi disseminated from the mosquito midgut at a rate of 31%, indicating that some genetic determinants of dissemination must lie within the non-structural (NS) protein genes or 3' non-coding region (NCR). We chose to investigate the roles of NS2A, NS4B, and the 3'NCR in YFV dissemination. Substitution of the 17D NS2A or NS4B into Asibi significantly attenuated YFV dissemination, demonstrating that this is a multigenic property. There was no difference in dissemination after substitution of the 17D 3'NCR.

Aedes↗

PubMed1989

Local reactivity, local resistance and systemic dissemination in Mycobacterium lepraemurium (MLM) infection.

Local reactivity measured as swelling of the infected footpad, local resistance to bacterial multiplication, and capacity to limit systemic dissemination were studied in C57BL, C3H/Bom, C3H/HeJ, and A/Sn mice inoculated with Mycobacterium lepraemurium. C57BL mice developed a strong local reaction with a sudden onset, and effectively limited local multiplication as well as systemic dissemination of bacteria to the liver and spleen as determined 19 weeks after the inoculation. C3H/Bom mice showed no local reaction, had high numbers of bacteria locally, and had extensive systemic dissemination of the infection. C3H/HeJ mice, on the other hand, developed a small local reaction and had less systemic dissemination of bacteria than C3H/Bom mice. In C57BL mice and in the two C3H substrains local reactivity, local resistance to infection, and resistance to systemic spread of the infection paralleled each other. In contrast, A/Sn mice showed a small local reaction, had the most extensive bacterial multiplication at the site of inoculation of the four mouse strains tested, and at the same time were the mice that most effectively restricted systemic dissemination of the infection. Thus, the mechanisms restricting local bacterial multiplication may be different from the mechanisms limiting bacterial dissemination. Neither bacterial growth locally at the site of subcutaneous inoculation in the footpad, nor systemic dissemination of the infection, followed a mouse strain pattern consistent with the Ity/Lsh/Bcg gene model. In experimental mycobacterial infection both local bacterial growth at the site of inoculation and systemic dissemination should be determined.

Animals↗

PubMed1995

Disseminated disease due to Mycobacterium avium complex in AIDS.

We retrospectively analysed 46 cases of disseminated infection with Mycobacterium avium complex (MAC) within a cohort of 702 HIV-infected patients in Edinburgh. Clinical features were compared with case-matched controls (AIDS cases without disseminated MAC), and survival and progression times were controlled for confounding variables that influence survival. Disseminated MAC was diagnosed antemortem in 18% of AIDS patients, and was the AIDS-defining diagnosis in 6% of all AIDS cases. Concomitant colonization of respiratory and gastrointestinal tracts was common (61% and 48%, respectively). In 58% of cases, CD4+ counts were < 10 cells/mm3 (median 6 cells/mm3). Weight loss, anaemia, leucopenia, and elevated liver transaminases and alkaline phosphatase were significantly more common among cases than controls. Therapy was given in 74%, and not tolerated in 32%. Following AIDS diagnosis, disseminated MAC incidence was 14% at one year, 25% at 2 years and 36% at 3 years. Median survival after disseminated MAC diagnosis was 6 months, with shorter survival in untreated cases. However, overall survival from AIDS diagnosis was not significantly different between patients who did or did not develop disseminated MAC. Disseminated MAC contributes significantly to AIDS morbidity, and its incidence increases with prolonged AIDS survival. Although survival following diagnosis is short, the development of disseminated MAC in AIDS probably does not affect overall survival. In cohorts with a low incidence, an alternative to prophylaxis might be surveillance and early diagnosis.

AIDS-Related Opportunistic Infections↗

PubMed1986

Disseminated intravascular coagulation.

Known variously as disseminated intravascular coagulation, defibrination consumption coagulopathy or, more simply, as defibrination, disseminated intravascular coagulation is a serious epiphenomenon that occurs most often as a complicating factor of an underlying disease process. Although frequently triggered by underlying disease such as infection or tumor, if not recognized and treated appropriately, disseminated intravascular coagulation alone may lead to the patient's death as a result of hemorrhage or thrombosis, or both, of vital organs. Frequently, it may only manifest itself as an abnormality of coagulation tests, causing no immediate problem for the patient, and potentially normalizing when the inciting cause is appropriately managed. The central process that marks disseminated intravascular coagulation is the generation of thrombin in the circulating blood by means of the activation of the coagulation mechanism, leading to the conversion of fibrinogen to fibrin, which, in turn, may lead to thrombosis mainly of the microcirculation. Because platelets and coagulation factors are consumed and fibrinolysis is enhanced during the coagulation process, hemorrhage may also ensue. Although disseminated intravascular coagulation is frequently encountered in medical and obstetric patients, the difficulty in diagnosis and controversy regarding optimal therapy are frustrating for both patient and physician. By understanding the pathophysiology of disseminated intravascular coagulation and combining clinical observation and laboratory data, one can arrive at the appropriate diagnosis. Therapy must be individualized, and assessment of the benefit versus risk ratio of intervention must be made. Early recognition of acute and life-threatening disseminated intravascular coagulation can be lifesaving with appropriate supportive measures.

Acute Disease↗

PubMed2002

Effective dissemination strategies.

Dissemination of research findings or other key messages is increasingly acknowledged as a vital yet complex process. In this paper, Philip Scullion sets out to explore and disentangle some of these complexities, examine examples of successful dissemination strategies and provide valuable insights. It is argued that the process of dissemination needs to be afforded greater emphasis by project-funding bodies, research supervisors, researchers, and those responsible for implementing changes in clinical practice. Important initiatives are acknowledged before the concept of dissemination is explored. The source, message, medium and target groups, all key elements in the dissemination process, are then examined. It is argued that dissemination needs to be carefully considered at the design stage of research projects in relation to each of these elements. This paper concludes that the current commitment to research and evidence-based practice will have limited impact on patient care until a similar commitment to dissemination is evident at both corporate and individual levels.

Databases as Topic↗

PubMedDate not supplied

Successful initial treatment with weekly 24-hour infusion of 5-fluorouracil and leucovorin in a rectal cancer patient with acute disseminated intravascular coagulation.

Cancer-associated acute disseminated intravascular coagulation is rare in colorectal cancer, but is rapidly fatal when present. We present a case of a 79-year-old male who developed acute disseminated intravascular coagulation one month after receiving Hartmann's procedure for his rectal cancer. Peripheral blood showed leucoerythroblastosis while marrow carcinomatosis was noted by bone marrow examination. Prompt chemotherapy with weekly 24-h infusion of 5-fluorouracil and leucovorin were administered and the acute disseminated intravascular coagulation gradually resolved after 2 cycles of treatment. A total of 10 cycles of weekly chemotherapy were administered. The patient died of pneumonia on the 83rd day after diagnosis of disseminated intravascular coagulation without evidence of acute disseminated intravascular coagulation and tumor progression. We suggest that if acute disseminated intravascular coagulation developed after surgery for rectal cancer, the cancer-related acute disseminated intravascular coagulation should be taken into consideration. The immediate administration of chemotherapy may save the patient in time.

Adenocarcinoma↗

PubMed2005

Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU-68).

SU6668 (TSU-68) is a small-molecule synthetic inhibitor of the angiogenic related receptor tyrosine kinases Flk-1/KDR, PDGFRbeta, and FGFR1. Using a mouse model of peritoneally disseminated ovarian cancer, we investigated whether SU6668 inhibits peritoneal dissemination and prolongs survival time. BALB/c nude mice were intraperitoneally (i.p.) inoculated with SHIN-3 (VEGF-hypersecretory) or KOC-2S (PDGF-hypersecretory) ovarian serous adenocarcinoma cells with marked peritoneal dissemination ability. From the day after i.p. inoculation of tumor cells, SU6668 was orally administered 6 times weekly at a daily dose of 100 mg/kg or 400 mg/kg. The SU6668-administered group and the vehicle-administered control group were compared for the number of tumor vascular endothelial cells, weight of peritoneally disseminated tumors, amount of ascitic fluid and survival time. As a result, these 3 parameters were significantly smaller in the SHIN-3-inoculated, SU6668-administered mice than in the control group (p = 0.03, p = 0.002, and p = 0.02, respectively). The mean survival time was significantly longer, at 58.1 +/- 11.2 days, in the SU6668-administered mice than that (34.5 +/- 8.8 days) in the control group (p = 0.002). Similarly, in the KOC-2S-inoculated mice, the oral administration of SU6668 significantly reduced these 3 parameters (p = 0.04, p = 0.04, and p = 0.03, respectively), and significantly prolonged survival (16.6 +/- 1.7 days vs. 11.0 +/- 0.7 days, p = 0.008). Thus, the oral administration of SU6668 inhibited angiogenesis and peritoneal dissemination and prolonged survival in mice with peritoneally disseminated ovarian cancer. These effects were observed with both the VEGF- and PDGF-hypersecretory cell lines. Our results suggest that molecular targeting with oral SU6668 will become a new therapeutic strategy targeting peritoneally disseminated ovarian cancer.

Adenocarcinoma↗

PubMed2000

Role of MMP-7 in the formation of peritoneal dissemination in gastric cancer.

BACKGROUND: Matrix metalloproteinase-7 (MMP-7) is an important matrix-degrading enzyme that has a large role in the invasion and metastasis of cancer. To discover the mechanism of the formation of peritoneal dissemination in gastric cancer, we studied the mRNA and protein expression of MMP-7 in primary gastric cancers and peritoneal dissemination.METHODS: MMP-7 expression in primary gastric cancers (136 patients) was studied by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), and the results were compared with chinicopathological parameters.RESULTS: MMP-7 mRNA was expressed in 28 (53%) of 53 primary gastric cancers, but not in normal gastric mucosa, fibroblasts, or mesothelial cells. An immunohistochemical method demonstrated that MMP-7 immunoreactivity was found on the cell membrane and cytoplasm of cancer cells. Among 136 primary tumors, 70 (53%) tumors overexpressed MMP-7, and MMP-7 tissue status had significant positive correlation with serosal involvement, lymph node metastasis, poor differentiation of cancer, and peritoneal dissemination. Patients with MMP-7-positive tumor had significantly poorer survival and more frequently died of peritoneal recurrence than did those with MMP-7-negative tumors. All 6 examined peritoneal disseminations expressed MMP-7 mRNA, and 13 of 14 peritoneal disseminations showed immunoreactivity to anti-human MMP-7 monoclonal antibody. Logistic regression analysis showed that MMP-7 immunohistological status was an independent risk factor for peritoneal dissemination, and patients with MMP-7 mRNA-positive tumors had a 9.9-fold higher relative risk for peritoneal metastasis.CONCLUSION: These results strongly suggest that MMP-7 may have a large role in the formation of peritoneal dissemination in gastric cancer, and that clonal selection of cancer cells with MMP-7 overexpression may occur during the invasion of intraperitoneal free cancer cells from the peritoneal surface into the subperitoneal tissue. MMP-7 tissue status in the primary tumor may be a good indicator of peritoneal dissemination.

Journal Article↗

PubMed2002

Detection of disseminated tumor cells in patients with cervical cancer.

PURPOSE: Detection of disseminated tumor cells in a cohort of patients presenting the entire spectrum of invasive cervical cancer. METHODS: Disseminated tumor cells were detected in blood samples taken at different times during surgery or in bone marrow aspirates by a HPV type-specific nested PCR enzyme immunoassay (n-PCR-EIA). A group of 24 patients with HPV-positive cervical cancers representing early and late stages were evaluated, and 15 patients with breast cancer and without HPV-related genital disease served as controls. RESULTS: Disseminated tumor cells were detected in blood samples and/or bone marrow aspirates of 6 of 24 patients. A significant association was found between detectable disseminated tumor cells and recurrent disease ( P=0.013) and between disseminated tumor cells and survival of the patients ( P=0.0054). There was also a clear association between the presence of disseminated tumor cells and tumor size and/or positive lymph node status which, however, was not statistically significant. There was no evidence of increased shedding of tumor cells during surgery. CONCLUSION: Detection of disseminated tumor cells in blood or bone marrow may prove to be of prognostic value, particularly for early-stage cervical cancers.

DNA, Viral↗