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J M Jessup

Publications and source records attributed to J M Jessup.

At least 37 records · Page 2Linked to original sources
PubMed1997

Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines.

Somatic mutations in DNA mismatch repair genes have been observed in sporadic tumors as well as cell lines and xenografts derived from such tumors implicating genetic defects of mismatch repair genes in the development of such tumors. However, the proportion of sporadic tumors in which mismatch repair genes have been inactivated has not been determined accurately. We have analyzed 66 sporadic colorectal tumors for the expression of hMLH1 by immunohistochemistry and identified 4 tumors that do not express hMLH1. These four colorectal tumors, a colon tumor cell line (SW48) and an endometrial tumor cell line (AN3CA), did not express hMLH1, despite the absence of mutations in its coding sequence. Cytosine methylation of the hMLH1 promoter region was found in these four colorectal tumors, whereas cytosine methylation of the hMLH1 promoter region was absent in adjacent normal tissue or in nine tumors that expressed hMLH1. In addition, cytosine methylation of the hMLH1 promoter region was observed in the SW48 and AN3CA cell lines that do not express hMLH1 but not in four tumor cell lines known to express hMLH1 mRNA. Our data indicate that DNA methylation is likely to be a common mode of mismatch repair gene inactivation in sporadic tumors.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Prospective evaluation of local excision for small rectal cancers.

OBJECTIVE: Most data on local excisions for rectal cancer are based on retrospective studies. We review the results of a prospective registry of patients eligible for local excision of rectal cancer using a transanal, transsphincteric, or transcoccygeal technique combined with multimodality therapy for lesions penetrating the muscularis propria (T2) or perirectal fat (T3). METHODS: Patients with lesions less than 4 cm in diameter and less than 10 cm from the dentate line, with no evidence of distant metastases or invasion into the perirectal fat, were eligible for local excision. Patients with invasion into the muscularis propria (T2) or greater (T3) received adjuvant chemoradiation therapy. RESULTS: Forty-eight patients have been followed prospectively. Average age is 63 years. Thirty-three patients underwent a transanal excision. Fifteen patients underwent either a transsphincteric or technique excision. There was no perioperative mortality. Pathology revealed 1 Tis, 21 T1, 21 T2, and 5 T3 cancers. Mean follow-up is 40.5 months. Cancer-related overall mortality was 4 percent. Overall local or distant recurrence rate was 8 percent (4/48). Recurrence appeared to be related to presence of a positive margin or aggressive histology (lymphatic invasion). Local recurrences were treated with salvage therapy. CONCLUSION: Local excision can be used selectively for small rectal cancers, with minimum morbidity. Recurrence rates are low (8 percent). Patients with either a positive margin or lymphatic invasion need to be considered for further therapy, including abdominoperineal resection, even with T1 lesions. Adjuvant chemoradiation appears to be a benefit for all T2 or T3 cancers.

Adenocarcinoma↗
PubMed1997

Association between sucrase-isomaltase and p53 expression in colorectal cancer.

BACKGROUND: Sucrase-isomaltase (SI) is a tissue-based phenotypic marker that is an independent prognostic factor in colorectal cancer (CRC). DF3 and galectin 3 are two other tissue-based markers that are upregulated during neoplastic transformation. Because p53 mutations are acquired during neoplastic progression, we reasoned that alterations in SI and p53 may be associated despite an apparent lack of biological interaction. METHODS: Paraffin sections from 183 patients who underwent surgery at New England Deaconess Hospital (NEDH) between 1965 and 1977 were analyzed first by immunohistochemistry (IHC) for the expression of the markers SI, DF3, and galectin 3, which were scored as absent or present. Paraffin sections from a second group of 59 patients who underwent surgery at NEDH between 1985 and 1992 were analyzed by IHC for the expression of p53 as well as SI, DF3, and galectin 3. p53 nuclear staining was scored as absent or present. Previous work has shown that p53 is mutated in all cells with nuclear staining and in 10% of tumors that are unstained. RESULTS: SI expression was not associated with the expression of either DF3 or galectin 3, and neither DF3 nor galectin 3 were prognostic factors in CRC. None of the phenotypic markers were associated with any of the clinicopathologic variables. However, 21 of 24 p53-positive cases (88%) expressed SI, whereas 15 of 35 p53-negative cases (43%) were also SI negative (p = 0.02, Fisher exact test). p53 expression was not associated with expression of DF3 or galectin 3. CONCLUSIONS: SI expression and p53 mutation are associated significantly in CRC. Although the mechanism underlying such an association in presently unknown, the association may define a subset of patients with a worse prognosis.

Antigens, Differentiation↗
PubMed1997

Induction of carcinoembryonic antigen expression in a three-dimensional culture system.

MIP-101 is a poorly differentiated human colon carcinoma cell line established from ascites that produces minimal amounts of carcinoembryonic antigen (CEA), a 180 kDa glycoprotein tumor marker, and nonspecific cross-reacting antigen (NCA), a related protein that has 50 and 90 kDa isoforms, in monolayer culture. However, MIP-101 produces CEA when implanted into the peritoneum of nude mice but not when implanted into subcutaneous tissue. We tested whether three-dimensional (3D) growth was a sufficient stimulus to produce CEA and NCA 50/90 in MIP-101 cells, because cells grow in 3D in vivo rather than in two-dimensions (2D) as occurs in monolayer cultures. To do this, MIP-101 cells were cultured on microcarrier beads in 3D cultures, either in static cultures as nonadherent aggregates or under dynamic conditions in a NASA-designed low shear stress bioreactor. MIP-101 cells proliferated well under all three conditions and increased CEA and NCA production three- to four-fold when grown in 3D cultures compared to MIP-101 cells growing logarithmically in monolayers. These results suggest that 3D growth in vitro simulates tumor function in vivo and that 3D growth by itself may enhance production of molecules that are associated with the metastatic process.

Animals↗
PubMed1997

Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas.

The cell-cycle inhibitor p27 is a potential tumor suppressor, but its gene has never been found inactivated in human tumors. Because cell-cycle regulation of p27 cellular abundance occurs at the post-transcriptional level, we analyzed p27 protein expression and degradation in human colorectal carcinomas. Proteasome-mediated degradation activity of p27 was compared with its protein levels in a subset of tumor samples. We found that carcinomas with low or absent p27 protein displayed enhanced proteolytic activity specific for p27, suggesting that low p27 expression can result from increased proteasome-mediated degradation rather than altered gene expression. Patients whose tumors expressed p27 had a median survival of 151 months, whereas patients who lacked p27 (10%) had a median survival of 69 months. By multivariate analysis, p27 was found to be an independent prognostic marker. Lack of p27 was associated with poor prognosis (2.9 risk ratio for death; P = 0.003). The absence of p27 protein expression is thus a powerful negative prognostic marker in colorectal carcinomas, particularly in stage II tumors, and thereby may help in the selection of patients who will benefit from adjuvant therapy. These data suggest that aggressive tumors may result from the selection of a clone or clones that lack p27 due to increased proteasome-mediated degradation.

Adenocarcinoma↗
PubMed1997

Gastric cancer surgical practice guidelines. Gastric Cancer Practice Guideline Committee.

The data described above suggest that the current management of gastric carcinoma requires a surgical resection. Identification of the number of lymph nodes that may be involved with cancer is an important prognosticator. Resection of involved lymph nodes is likely to decrease the morbidity of locoregional recurrence. However, this has not been adequately addressed in the studies performed to date. Nonetheless, accurate staging is an essential goal of the primary therapy of gastric carcinoma. The limits of resection for a gastric cancer are outlined in the guidelines (see page 1068). Administration of adjuvant therapy, such as chemotherapy or radiation therapy, remains controversial and is the subject of ongoing clinical research. Until a prospective, randomized trial demonstrates a significant improvement in survival, there remains little or no basis for the addition of adjuvant therapy outside the context of a clinical trial.

Carcinoma↗
PubMed1996

The DCC protein and prognosis in colorectal cancer.

BACKGROUND: Allelic loss of chromosome 18q predicts a poor outcome in patients with stage II colorectal cancer. Although the specific gene inactivated by this allelic loss has not been elucidated, the DCC (deleted in colorectal cancer) gene is a candidate. We investigated whether the expression of the DCC protein in tumor cells is a prognostic marker in colorectal carcinoma. METHODS: The expression of DCC was evaluated immunohistochemically in 132 paraffin-embedded samples from patients with curatively resected stage II and III colorectal carcinomas. The Cox proportional-hazards model was used to adjust for covariates including age, sex, tumor site, degree of tumor differentiation, and use of adjuvant therapy. RESULTS: The expression of DCC was a strong positive predictive factor for survival in both stage II and stage III colorectal carcinomas. In patients with stage II disease whose tumors expressed DCC, the five-year survival rate was 94.3 percent, whereas in patients with DCC-negative tumors, the survival rate was 61.6 percent (P<0.001). In patients with stage III disease, the respective survival rates were 59.3 percent and 33.2 percent (P=0.03). CONCLUSIONS: DCC is a prognostic marker in patients with stage II or stage III colorectal cancer. In stage II colorectal carcinomas, the absence of DCC identifies a subgroup of patients with lesions that behave like stage III cancers. These findings may thus have therapeutic implications in this group of patients.

Aged↗
PubMed1996

Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers.

Introduction of tumor markers into routine clinical practice has been poorly controlled, with few criteria or guidelines as to how such markers should be used. We propose a Tumor Marker Utility Grading System (TMUGS) to evaluate the clinical utility of tumor markers and to establish an investigational agenda for evaluation of new tumor markers. A Tumor Marker Utility Grading Worksheet has been designed. The initial portion of this worksheet is used to clarify the precise characteristics of the marker in question. These characteristics include the marker designation, the molecule and/or substance and the relevant alteration from normalcy, the assay format and reagents, the specimen type, and the neoplastic disease for which the marker is being evaluated. To determine the clinical utility of each marker, one of several potential uses must be designated, including risk assessment, screening, differential diagnosis, prognosis, and monitoring clinical course. For each of these uses, associations between marker assay results and expected biologic process and end points must be determined. However, knowledge of tumor marker data should contribute to a decision in practice that results in a more favorable clinical outcome for the patient, including increased overall survival, increased disease-free survival, improvement in quality of life, or reduction in cost of care. Semiquantitative utility scales have been developed for each end point. The only markers recommended for use in routine clinical practice are those that are assigned utility scores of "++" or " " on a 6-point scale (ranging from 0 to ) in the categories relative to more favorable clinical outcomes. Each utility score assignment should be supported by documentation of the level of evidence used to evaluate the marker. TMUGS will establish a standardized analytic technique to evaluate clinical utility of known and future tumor markers. It should result in improved patient outcomes and more cost-efficient investigation and application of tumor markers.

Biomarkers, Tumor↗
PubMed1996

The National Cancer Data Base report on patterns of hospital reporting.

BACKGROUND: Previous Commission on Cancer data from the National Cancer Data Base (NCDB) have examined time trends in stage of disease, treatment patterns, and survival for selected cancers. The most current (1993) data are described here. METHODS: Five calls for data have yielded a total of 3,700,000 cases for the years 1985 through 1993, including 477,679 cases for 1988, and 608,593 cases for 1993, from hospital cancer registries across the U.S. RESULTS: The most recent call for data for 1993 comprised 52% of the estimated new cases of cancer in the U.S. The country was comprised of 6 regions, with the Mountain and Southeast regions having the highest regional reporting of new cases of cancer (69% and 55%, respectively) and the Northeast and Pacific regions having the lowest (47% each). Approximately 96% of patients received their treatment at the reporting hospital. The 4 most common carcinomas were breast (15.7%), lung (14.6%), prostate (14.2%), and colon (7.5%) and comprised the majority of new cases. Trends in patterns of care for breast carcinoma were analyzed for possible bias in the 1988 and 1993 periods. When hospitals reporting only in 1988 or in 1993 were compared with hospitals reporting at both time points, the only differences were small differences in ethnic participation. These differences were less than 1.5% in the proportion of African Americans reported in the different time periods. There were no significant differences in the downstaging of breast carcinoma, or the role of conservative surgery or adjuvant radiation therapy. CONCLUSIONS: The NCDB is a cancer management and outcomes data base for health care organizations that presently comprises 52% of the estimated new cases in the U.S. This will increase to 80% as the approved hospitals of the Commission on Cancer are required to report to the NCDB. Comparison of breast carcinoma findings at two time periods appeared similar regardless of hospital reporting set (i.e., set of hospitals reporting for one period versus both periods).

Adolescent↗
PubMed1996

The National Cancer Data Base. Report on colon cancer.

BACKGROUND: Commission on Cancer data from the National Cancer Data Base (NCDB) report time trends in stage of disease, treatment patterns, and survival for patients with selected cancers. The most current data (1993) for patients with colon cancer are described. METHODS: Five calls for data yielded 3,700,000 cases of cancer for the years 1985 through 1993 from hospital cancer registeries across the U.S., including 36,937 cases of colon cancer from 1988 and 44,812 from 1993. RESULTS: Interesting trends are as follows: (1) the elderly ( > 80 years) present with earlier stage disease than younger patients; (2) the National Cancer Institute recognized cancer centers have more patients with advanced disease than other types of hospitals; (3) all ethnic groups have generally similar stages of disease at presentation, except for African-Americans who have a slightly higher incidence of Stage IV disease; (4) the proximal migration of the primary cancer continues with 54.7% of primary colon cancer arising in the right colon in 1993 compared with 50.9% in 1988; (5) an interaction between grade and stage of cancer seems present; and (6) patients with Stage III colon cancer who received adjuvant chemotherapy had a 5% improvement in 5-year relative survival. CONCLUSIONS: The NCDB data are useful for reporting what cancer treatments are being administered and what outcomes are occurring in the U.S. The data suggest an important biologic role for grade of cancer. They also suggest that African-Americans and other ethnic groups have the same outcome as non-Hispanic whites but that access to medical care may still be less. Finally, the utility of adjuvant therapy for Stage III colon cancer may just be beginning to be appreciated.

Aged↗
PubMed1996

Implantation of human colorectal carcinoma cells in the liver studied by in vivo fluorescence videomicroscopy.

In vivo fluorescence videomicroscopy (IVFM) was used to analyse the behavior of weakly and highly metastatic human colorectal carcinoma (CRC) cells during implantation in the liver. A highly metastatic human CRC cell line, CX-1, and a weakly metastatic line, Clone A, were double-labeled with rhodamine B isothiocyanate-dextran (Rd-Dx) to locate cells and with calcein AM to assess cell metabolic activity in an experimental metastasis model. Double-labeled CRC cells (2.0 x 10(6)) were injected into the spleens of groups of nude mice and the livers observed by IVFM over the next 72 h. CRC cells were implanted within 30 s after injection into either portal venules or the proximal third of hepatic sinusoids. Approximately 0.5% of CRC cells traversed the liver through portal-central venous shunts and implanted in the lung. The number of CX-1 cells in the liver was similar to that of Clone A cells during the first 12 h. However, more CX-1 cells than Clone A cells remained in the liver at 4 h and were in groups of 8-12 cells whereas only a few, single Clone A cells were detected in the liver at 72 h. Not all Clone A cells are committed to die within 4 h of implantation because cells harvested 4 h after hepatic implantation proliferated normally in vitro when removed from the hepatic microenvironment. Since the stress of mechanical deformation during implantation may cause differences in cell survival, CX-1 and Clone A cells were passed through filters with 8 microM pores in vitro at 10-15 cm of water pressure to recreate the trauma of hepatic implantation. Approximately 50% of both CX-1 and Clone A cells were lysed. Furthermore, both CRC lines remained metabolically active when co-cultivated with liver cells for at least 24 h in vitro. Thus, the difference in metastatic potential between the two CRC lines may reside in their response to the combination of mechanical implantation and subsequent growth in the liver parenchyma.

Animals↗
PubMed1996

n-3 fatty acids decrease colonic epithelial cell proliferation in high-risk bowel mucosa.

The n-3 fatty acids (C20:5, eicosapentaenoic acid; c22:6, docosahexaenoic acid) may be important in the development, growth, and metastasis of colon cancer, a leading cause of death in North America. Patients who have had a bowel neoplasm have a high risk of developing a second neoplasm, and this risk is associated with a high percentage of cells correspond to the S phase of bromodeoxyuridine (BrdUrd) labeling in mucosal epithelial cells. To determine the effect of n-3 fatty acid supplementation on DNA synthesis of rectal mucosa, patients with stage 1 or stage 2 colon carcinoma or adenomatous polyps were randomized to consume either 9 g/d n-3 fatty acid capsules or 9 g/d placebo capsules. Plasma phospholipid fatty acid analysis and proctoscopic mucosal biopsies were performed at baseline, 3, and 6 mon. Colonic crypts were isolated from the mucosa, disassociated with enzymes, and incubated with BrdUrd, and %S phase was measured by flow cytometry. The plasma phospholipid n-6/n-3 ratio was determined by gas chromatography. Supplement compliance was assessed by plasma phospholipid n-6/n-3 ratio. Mean capsule consumption in these two group was 82%. Prior to supplementation, there were no significant differences in the %S phase and the plasma n-6/n-3 ratio between these groups. Patients whose colonic epithelial cells indicated hyperproliferation at baseline showed a strongly positive correlation to the %S phase of BrdUrd uptake and the n-6/n-3 ratio. There was no significant change after n-3 treatment in patients with low baseline. Those in the placebo group showed no significant difference in n-6/n-3 ratio, although there was an increase in the %S phase of BrdUrd uptake at 6 mon. The n-3 group did not have significant side effects, and polyps were not found after completing 12 mon of n-3 fatty acid supplementation. This study suggests that n-3 fatty acid may be a useful chemopreventive agent in some patients as reflected in a plasma biomarker of colon tumor growth and metastasis. A low plasma phospholipid n-6/n-3 fatty acid ratio may serve as a nutritional marker that is associated with colonic epithelial cell hyperproliferation in the n-3-supplemented group as compared with the placebo group. Characteristics of mucosal proliferation at baseline may be a crucial factor for the effect of n-3 fatty acid supplementation.

Cell Division↗
PubMed1995

The effect of transfection of the CEA gene on the metastatic behavior of the human colorectal cancer cell line MIP-101.

Carcinoembryonic antigen (CEA) has been shown to increase the metastatic potential of some human colorectal cancer cell lines. To investigate further the mechanisms involved we have produced three clones (6, 8 and 17) from the poorly differentiated human colorectal cancer cell line MIP-101 that have been transfected with the full length cDNA encoding for human carcinoembryonic antigen (CEA). They produce CEA with a mol. wt. of 180000 by Western blotting and secrete it into the culture medium. Clone 6 is a high CEA producer, clones 8 and 17 are intermediate producers. The doubling time for clone 8 was similar to that of the parent cell line while clones 6 and 17 had doubling times nearly twice that of the parent cells. These clones are tumorigenic when injected subcutaneously in nude mice are positive for CEA by immunoperoxidase staining and the mice have elevated blood levels of CEA. Clone 6 formed large aggregates in culture while clone 17 formed smaller aggregates. Clone 8 behaved like the parent cell line with rare cell/cell contact. Clones 6 and 17 also adhered to CEA coated plastic while clone 8, a neo-transfected control and the parent cell line did not. A significant increase in the incidence of hepatic tumors was observed with clone 6 (P < 0.01) and clone 17 (P < 0.02) following intrasplenic injection into nude mice. Immunohistopathology of the hepatic tumors showed strong CEA staining from clones 6 and 17 with weak staining from clone 8. The parent cell line was negative for CEA as were the neo-transfected controls. Of the neo controls none of 10 had liver colonies. Mice injected with clone 6 which developed liver metastasis had the highest plasma levels of CEA (37.3 +/- 8.8 ng/ml). We observed strong CEA staining in Kupffer cells in the normal liver adjacent to the CEA producing tumors. This study provides further evidence for the involvement of CEA in the metastatic process.

Adenocarcinoma↗
PubMed1995

Carcinoembryonic antigen and other glycoconjugates act as ligands for galectin-3 in human colon carcinoma cells.

Galectin-1 and galectin-3, galactoside-binding lectins with molecular weights of M(r) 14,500 and 31,000, respectively, are expressed in normal and malignant cells and have been implicated in regulation of cell growth, adhesion, and metastasis. We analyzed the expression of galectins in 21 cultured human colon carcinoma cell lines by immunoblotting. Galectin-1 was detected in only 7, whereas galectin-3 was found in 20 of the cell lines. KM12 cells, which express only galectin-3, were used to isolate this lectin by affinity chromatography, and the purified lectin was used to identify complementary glycoconjugates by blotting. Galectin-3 was shown to bind to human laminin, carcinoembryonic antigen, and lysosome-associated membrane glycoproteins, which are involved in cell adhesion. Galectin-3 was localized on the KM12 cell surface and colocalized with carcinoembryonic antigen. Several endogenous glycoproteins and cell surface proteins of molecular weights in the range M(r) 58,000 to > 200,000, including carcinoembryonic antigen and lysosome-associated membrane glycoproteins, were identified as galectin-3 ligands by coimmunoprecipitation with and affinity chromatography on immobilized galectin-3. These data demonstrate that galectin-3 interacts with several adhesion molecules and suggest that this lectin may have a role in human colon carcinoma cell adhesion.

Antigens, CD↗
PubMed1995

Sucrase-isomaltase is an independent prognostic marker for colorectal carcinoma.

PURPOSE: Expression of disaccharidase sucrase-isomaltase (SI) is significantly enhanced during neoplastic transformation of colonic epithelium. Our study was designed to determine whether expression of SI within primary tumors was significantly associated with survival in patients with colorectal carcinoma (CRC). METHODS: SI expression was analyzed by immunohistochemistry in paraffin sections from 182 Stage I to III CRC that had been resected for cure at the New England Deaconess Hospital between 1965 and 1977. Expression was scored as absent or present in 1 to 50 percent or more than 50 percent of tumor cells. Associations were explored among SI expression, other clinical or pathologic variables, and overall survival. The data set is mature, with 91 (56 percent) patients who had died of CRC at a median follow-up of 96 months. RESULTS: Fifty-five percent of primary CRC expressed SI. When the multivariate Cox analysis was performed, nodal status, T stage, primary site, grade, and SI expression were independent covariates. SI expression was not associated with the expression of other clinicopathologic variables but increased the risk of death from colorectal carcinoma by 1.83-fold. DISCUSSION: These results indicate that SI is a prognostic marker for CRC that is independent of stage-related variables in patients who have undergone potentially curative resections.

Aged↗
PubMed1994

Intraoperative ultrasound imaging of the liver at the time of colorectal cancer resection.

OBJECTIVES: To evaluate the accuracy of intraoperative ultrasound (IOUS) liver imaging at the time of primary colorectal cancer resection, which might eliminate incurable patients from adjuvant chemotherapy trials or permit earlier resection of curable metastases. DESIGN: A prospective trial of routine IOUS liver imaging during resections of primary colorectal cancer. The rate of detection of occult metastases by IOUS imaging alone and the false-negative rate over 22.7 months of follow-up were determined. SETTING: A tertiary care referral center in Boston, Mass. PATIENTS: Fifty-five patients undergoing 56 operations for colorectal carcinoma between May 1990 and June 1992. MAIN OUTCOME MEASURES: The rate of detection, by IOUS imaging alone, of otherwise occult hepatic metastases, the total number of patients with metastases detected at any time during follow-up, and the rate of false-negative findings on IOUS imaging and direct examination. RESULTS: Occult hepatic metastases were detected by IOUS imaging alone in 5% of patients. Restriction of IOUS imaging to patients with T3 or T4 lesions or recurrent cancers would have identified all metastases and increased the detection rate to 10%. Occult metastases were detected by IOUS imaging alone in 12.5% of patients with T3, N0 lesions. The rate of false-negative findings on IOUS imaging was 13% overall, 0% for patients with T1 or T2 lesions, 3% for patients with node-negative findings, and 7% for patients with T3, N0 lesions. CONCLUSIONS: The small increment in the detection of occult metastases by IOUS liver imaging does not warrant its use in all patients with colorectal cancer. Selective use in patients with T3 or T4 lesions or recurrent cancers increased the incremental gain in detection. The observed frequency of occult metastases in patients with T3, N0 lesions is sufficient to impact on results of adjuvant chemotherapy trials. Longer follow-up in more patients is needed to determine whether a negative IOUS study is an additional favorable prognosticator in patients with T1 and T2 lesions and node-negative findings.

Adult↗