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L Kan

Publications and source records attributed to L Kan.

At least 19 recordsLinked to original sources
PubMed1997

Post screen-detected breast cancer within the Screening Mammography Program of British Columbia.

The histological characteristics and extent of mammographic density were compared between 170 post screen-detected (PSD) breast cancers and 466 screen-detected (SD) breast cancers in women attending the Screening Mammography Program of British Columbia. In addition, methods of detection and clinical presentation for the PSD cancers were examined. Invasive ductal, comedo, and medullary carcinoma were significantly more common in PSD cancer in women under age 50 years, and invasive ductal carcinoma in women over age 50 years. Mammographic density was more common in PSD cancers for all age groups under 70 years. The majority of PSD cancers were node negative with no evidence of metastases; however, they tended to be of more advanced stage than SD cancer. Most PSD cancers regardless of age were initially found by the woman herself, presenting as a palpable mass, and the likelihood of being detected within 12 months of the last screening mammogram was higher at younger ages.

Age Factors↗
PubMed1995

Effect of selective cytosine methylation and hydration on the conformations of DNA triple helices containing a TTTT loop structure by FT-IR spectroscopy.

5-Methylcytosines have been introduced into triplex-forming-oligonucleotides and shown to extend the pH range over which a triplex forms with a homopurine-homopyrimidine tract of duplex DNA. As a host strand, an oligodeoxypyrimidine with a base sequence of 5'-d(TC)3T4(CT)3 ([CC]) was designed to form a hairpin triplex with a 5'-d-A(GA)2G ([AG6]) purine strand at acidic pH (Tsay, et al., (1995) J. Biomol. Str. Dyn., 13, 1235-1245). We here present results obtained by FT-IR spectroscopy concerning the conformation of the hairpin triplex as a function of the selective substitution of cytosines by 5-methylcytosines in the host strand. Namely, cytosines are substituted by 5-methylcytosines in either the 3'-pyrimidine portion ([CM]) or the 5'-pyrimidine portion ([MC]) or in both ([MM]) of the host strand. The acidic-induced transitions of the equimolar mixtures of the purine target with either of the four pyrimidine oligomers gives rise to different apparent pK values, i.e., [MM].[AG6] (6.2) > [MC].[AG6] (6.0) > [CM].[AG6] (5.7) > [CC].[AG6] (5.2) > single-stranded oligopyrimidines (4.6 +/- 0.2), indicating that cytosine methylation expands the pH range compatible with the hairpin triplex formation regardless of whether the substitution is in the 5'-pyrimidine (Hoogsteen) portion or in the 3'-pyrimidine (Watson-Crick) portion. Thermal denaturation profiles indicated that all the triplexes denatured in a monophasic manner in the pH range of 4.0 to 7.0, and that cytosine methylations in any position of the 16-base pyrimidine oligomer increase the stability of the hairpin triplex DNA. IR spectra recorded in D2O and H2O solutions revealed that cytosine methylation does not significantly influence the conformation of triplex DNA in solution, i.e., all the four triplexes accept a similar sugar conformation, and predominately take on a S-type sugar pucker with a relative proportion of two S-type sugars for one N-type. Furthermore, we also investigated the effect of relative humidity (RH) on the conformation of triplex MC.AG6 in hydrated films, and found that the conformational change induced by the decrease of RH, from predominant S-type to primary N-type sugar pucker, might first occur in the purine strand at 86% RH.

Absorption↗
PubMed1995

Quality-oriented mass mammography screening.

PURPOSE: To demonstrate the ability of a mass mammography screening program to provide consistently high-quality mammography screening, while at the same time sustain a large volume of patients to keep the cost of mammography low. MATERIALS AND METHODS: A public-funded, mass mammography screening program, begun in 1988, is currently being conducted in five Canadian provinces. For the Screening Mammography Program of British Columbia, complete follow-up data are available for the first 57 months of operation. During that time, the program expanded from one center with five radiologist screeners to 14 centers with 30 radiologist screeners. There were 201,937 examinations performed on 128,325 women, 35% of whom were younger than 50 years. RESULTS: There were 802 cancers detected at an overall rate of 6.2 per 1,000 women (2.8 per 1,000 in women younger than 50 years and 8.1 per 1,000 in women older than 50 years). In the women younger than 50 years, 90 (72%) of the cancers were stage 0 or stage I, and the axillary lymph nodes were involved in 14 (11%). In the women 50 years or older, 496 (73%) of the cancers were stage 0 or stage 1, and the axillary lymph nodes were involved in 97 (14%). CONCLUSION: If quality is carefully controlled, the results of a mass screening program can be either maintained or improved. For both age groups, the prognostic characteristics are similar.

Breast Neoplasms↗
PubMed1994

Screening mammography in British Columbia: 1988-1993.

Breast carcinoma continues to be the most common cause of death due to malignancy for women in Canada. The Screening Mammography Program of British Columbia, the first provincial screening program in Canada, was established in 1988 with funding from the Ministry of Health to diagnose the disease as early as possible. The program has grown rapidly, increasing from 7,100 examinations in a pilot project in 1988 to 89,390 examinations between April 1, 1992 and March 31, 1993 for a cumulative total of 201,937 examinations of 128,325 women, and it now offers free screening mammography throughout the province. The program has maintained quality control standards and low cost per mammogram while developing different operational models for the differing requirements of the various areas of the province. Similar proportions of women older or younger than age 50 have favourable characteristics such as small size of tumor (median: 15 to 16 mm) and negative lymph nodes (86% to 89%).

Breast Neoplasms↗
PubMed1994

Interval breast cancers in the Screening Mammography Program of British Columbia: analysis and classification.

OBJECTIVE: Interval cancers in an annual mammography screening program are defined as cancers detected within 12 months after a mammographic screening in which findings are considered normal. Our objective was to analyze interval cancers for histologic type, tumor size, staging, and histologic grade. A classification for interval cancers is presented. Detection of interval cancers is an integral part of quality control and is required for the establishment of sensitivity rates for screening mammography, a necessary part of implementing the recommendations for breast cancer screening. MATERIALS AND METHODS: A total of 47,583 mammographic screening examinations of 38,219 women were available for review for the period of July 1988 to March 1991. Linkage with the provincial population-based cancer registry provided identification of all interval cancers of the breast. Histologic analysis of breast cancers was provided by an internationally recognized breast cancer pathologist who interpreted the specimens twice. RESULTS: A total of 207 breast cancers were detected at mammographic screening (true-positive cancers) during the first 33 months of the program, and 37 interval cancers were identified during the 33 months of screening plus a 12-month interval. Blinded review by three radiologists experienced in screening mammography resulted in classification of 21 of 37 cases as true interval cancers and 16 cases as misses. No interval cancers were missed because of poor mammographic technique. The sensitivity of screening mammography was 85%, 63% for patients less than 50 years old and 89% for patients more than 50 years old. The specificity was 93% for all patients (both younger and older than 50 years). CONCLUSION: The availability of a population-based cancer registry in the province of British Columbia makes an accurate determination of interval cancers and sensitivity rates possible. These data are essential for quality analysis, program planning, and education of radiologists in screening mammography. There were more true interval cancers than misses, and histologic analysis demonstrated that the majority of interval cancers were in stages I and II.

Adult↗
PubMed1992

P-glycoprotein expression and multidrug resistance in adrenocortical carcinoma.

BACKGROUND: The response of adrenocortical carcinoma (ACC) to adjuvant chemotherapy has been disappointing with no significant impact on survival. The normal adrenal cortex has very high levels of P-glycoprotein, an energy-dependent efflux pump of a variety of structurally unrelated chemotherapeutic agents. P-glycoprotein has been implicated as a cause of multidrug resistance in a variety of neoplasms. The purpose of this study was to evaluate P-glycoprotein expression in ACC. METHODS: Eleven patients with ACC had paraffin-embedded tumor evaluated for P-glycoprotein expression. These were analyzed by immunohistochemistry assay with a battery of four anti-P-glycoprotein antibodies (MRK-16, JSB-1, UIC-2, MDR). RESULTS: All eleven cases showed intense, predominantly membrane immunoreactivity for P-glycoprotein. In 10 of the cases, most tumor cells were immunoreactive with at least three antibodies, and six of 11 cases were positive for all four antibodies. In this small series no correlation existed between P-glycoprotein expression and tumor grade, stage of disease, or survival. CONCLUSIONS: All 11 cases of ACC studied showed P-glycoprotein expression, which was similar to the normal adrenal cortex. This possible mechanism of multidrug resistance may help explain the significant chemoresistance seen in ACC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Effects of social relationships on survival for women with breast cancer: a prospective study.

In this study we examine the relationship between a woman's social contexts at the time of diagnosis and her chances of having survived breast cancer four years later. A cohort of 133 women were followed prospectively after initial diagnosis and treatment and data were obtained from a questionnaire mailed soon after diagnosis and from hospital charts. Using multivariate methods to examine predictors of survival, two clinical factors, pathologic nodal status and clinical stage of disease, were significantly associated with survival. In addition we found significant and independent effects on survival of: number of supportive friends, number of supportive persons, whether the woman worked, whether she was unmarried, the extent of contact with friends and the size of her social network. Thus, the woman's social context, particularly contexts of friendship and work outside the home, are statistically important for survival. Using existing literature, further data analyses and interviews with some survivors, we speculate on the ways in which social contexts may influence survival and suggest research methods suitable to this question.

Adult↗
PubMed1990

Activation of human T cell clones through the UM4D4/CDw60 surface antigen.

UM4D4 is a recently defined antigen that is expressed on approximately 25% of peripheral blood T cells, but on the majority of T cells in inflammatory synovial fluid. Anti-UM4D4 activates peripheral blood T cells in the presence of accessory cells and/or phorbol ester. UM4D4 has been assigned to a new antigen cluster termed CDw60. The present study examined the ability of anti-UM4D4 to activate T cell clones derived from the synovial fluid of patients with rheumatoid arthritis. UM4D4 was expressed at varying levels on both lectin-generated and antigen-specific clones, including clones of CD4+, CD8+, and CD4-CD8- phenotypes. Anti-UM4D4 used in soluble form as a single stimulus was typically mitogenic for the CD4+ and some of the CD8+ clones, but not for the CD4-CD8- clones. Phorbol ester boosted the response to anti-UM4D4 in some clones, had no effect in others, and diminished the responses in some cases. In contrast to anti-UM4D4, anti-CD3 was generally not mitogenic in soluble form, although it was mitogenic when conjugated to beads. The data show that T cell clones derived from an inflammatory T cell infiltrate can be readily activated through the UM4D4/CDw60 antigen.

Antibodies, Monoclonal↗
PubMed1990

Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen.

Accumulating evidence implicates a central role for synovial T cells in the pathogenesis of rheumatoid arthritis, but the activation pathways that drive proliferation and effector function of these cells are not known. We have recently generated a novel monoclonal antibody against a rheumatoid synovial T cell line that recognizes an antigen termed UM4D4 (CDw60). This antigen is expressed on a minority of peripheral blood T cells, and represents the surface component of a distinct pathway of human T cell activation. The current studies were performed to examine the expression and function of UM4D4 on T cells obtained from synovial fluid and synovial membranes of patients with rheumatoid arthritis and other forms of inflammatory joint disease. The UM4D4 antigen is expressed at high surface density on about three-fourths of synovial fluid T cells and on a small subset of synovial fluid natural killer cells; in synovial tissue it is present on more than 90% of T cells in lymphoid aggregates, and on approximately 50% of T cells in stromal infiltrates In addition, UM4D4 is expressed in synovial tissue on a previously undescribed population of HLA-DR/DP-negative non-T cells with a dendritic morphology. Anti-UM4D4 was co-mitogenic for both RA and non-RA synovial fluid mononuclear cells, and induced IL-2 receptor expression. The UM4D4/CDw60 antigen may represent a functional activation pathway for synovial compartment T cells, which could play an important role in the pathogenesis of inflammatory arthritis.

Adult↗
PubMed1989

Expression and function of the UM4D4 antigen in human thymus.

UM4D4 is a newly identified T cell surface molecule, distinct from the Ag receptor and CD2, which is expressed on 25% of peripheral blood T cells, resting or activated. Monoclonal anti-UM4D4 is mitogenic for T cells and T cell clones. Since alternative activation pathways independent of Ag/MHC recognition may be important in thymic differentiation, the expression and function of UM4D4 was examined in human thymus. UM4D4 was found on the surface of 6% of thymocytes. All thymocyte subsets contained UM4D4+ cells but expression was greatest on thymocytes that were CD1- (12%), CD3+ (11%) and especially CD4-CD8- (18%). CD3+CD4- CD8- cells, most of which bear the gamma delta-receptor, were greater than or equal to 50% + for UM4D4. Moreover, anti-UM4D4 was comitogenic for thymocytes together with PMA or IL-2. Anti-UM4D4 also reacted strongly with a subset of thymic epithelial cells in both cortex and medulla. Dual color fluorescence microscopy, with anti-UM4D4 and antibodies to other thymic epithelial Ag, showed UM4D4 expression on neuroendocrine thymic epithelium but not on thymic fibrous stroma. Thus, UM4D4 is expressed on, and represents an activation pathway for, a subset of thymic T cells. In addition, this determinant, initially identified as a novel T cell activating molecule, is broadly expressed by neuroendocrine thymic epithelium. Although the function of UM4D4 on the thymic epithelial cells is not yet clear, it is possible that UM4D4 represents a pathway for the functional activation of a subset of the thymic epithelium as well as a subset of thymocytes, thus playing a dual role in T cell differentiation.

Antibodies, Monoclonal↗
PubMed1989

Clonal heterogeneity of synovial fluid T lymphocytes from patients with rheumatoid arthritis.

Although substantial evidence suggests that synovial T lymphocytes are critical in the pathogenesis of rheumatoid arthritis (RA), little is known regarding their antigenic specificities, antigen receptor gene rearrangements, and mechanisms of activation. To assess the extent of expansion of specific clones among RA synovial fluid T cells, Southern blot analyses of T-cell receptor (TCR) gene rearrangements were performed on 40 RA synovial fluid T-cell clones, as well as on both fresh and polyclonally activated T cells from RA synovial fluid, RA peripheral blood, and normal peripheral blood. Two of the clones had identical TCR rearrangement patterns, but the remainder were unique. The nonclonal RA T-cell samples showed the same pattern of TCR beta-chain rearrangement that was observed among normal peripheral blood T cells, indicating no dominant clonal T-cell population in these samples. It was noted that with sufficient exposure of autoradiograms of the Southern blots, discrete TCR gene rearrangements, representing in some cases common D beta J beta (D, diversity; J, joining) rearrangements, were evident in T cells from peripheral blood of normal individuals and patients with RA, as well as T cells from RA synovial fluid. Taken together, the findings indicate that only a minor degree of oligoclonality can be demonstrated among T lymphocytes from RA synovial fluid.

Arthritis, Rheumatoid↗
PubMed1988

Nuclear magnetic resonance studies of cis-syn, trans-syn, and 6-4 photodimers of thymidylyl(3'-5')thymidine monophosphate and cis-syn photodimers of thymidylyl(3'-5')thymidine cyanoethyl phosphotriester.

Three out of four possible photodimers of thymidylyl(3'-5')thymidine monophosphates (i.e., cis-syn, 6-4, and one of the trans-syn) and two structural isomers (i.e., R and S forms) of cis-syn-thymidylyl(3'-5')thymidine cyanoethyl phosphotriester have been isolated and purified from the reaction mixtures after UV irradiation and studied by multinuclear magnetic resonance Spectroscopy. All five inter thymine base linked photodimers have grossly similar structures which are quite different from those of the parent thymidylyl(3'-5')thymidine. The base of Tp- is in the syn conformation, and that of -pT it is in the anti conformation. The sugar puckering of Tp- is dominated by the 2E conformer, but in -pT it is in 4E; except for the conformer around C5'-O5' bond, the 6-4 isomer is very similar to those of cis-syn and trans-syn conformation. As expected, there are sugar-phosphate backbone distortions in the phosphotriesters, due to the neutralization of the negative charge of the phosphate. In general the structures of all five photodimers are very close to those of the cis-syn photodimer of thymidylyl(3'-5')thymidine monophosphate cyanoethyl ester as studied by X-ray diffraction [Cadet, J., Voituriez, L., Hruska, F. E., & Grand, A. (1985) Biopolymers 24, 897-903; Hruska, F. E., Voituriez, L., Grand, A., & Cadet, J. (1986) Biopolymers 25, 1401-1417]. While the trans-syn photodimer has two structural isomers, only one [C6(of Tp-)-R] was produced by the UV irradiation and studied.

Dinucleoside Phosphates↗
PubMed1988

A novel pathway of human T lymphocyte activation. Identification by a monoclonal antibody generated against a rheumatoid synovial T cell line.

Substantial evidence indicates that compartmentalized infiltrates of T lymphocytes are central to the pathogenesis of autoimmune diseases such as rheumatoid arthritis, but the mechanisms by which such cells become activated remain unknown. To define surface components of activation pathways important in the function of these cells, we have generated mAb against a rheumatoid synovial T cell line. One such antibody, termed anti-UM4D4, reacts with an Ag, termed UM4D4, which is strongly expressed on most rheumatoid synovial T cell lines and clones, and on a subset of peripheral blood T cells, resting or activated. Anti-UM4D4 is mitogenic in soluble form for PBMC and certain T cell clones, and is comitogenic with the phorbol ester PMA for purified resting T lymphocytes. These functional effects are similar to those previously observed with antibodies to epitopes of CD2 and CD3, surface Ag involved in two well defined pathways of human T cell activation. Binding of anti-UM4D4 to T cells is not, however, blocked by antibodies directed at various epitopes of CD2 and CD3. Moreover, UM4D4 does not comodulate with CD3, and is expressed on a T cell line that lacks CD2, CD3, and CD28. The data, therefore, indicate that anti-UM4D4 identifies a T cell activation pathway, distinct from those previously described, that could play a role in the pathogenesis of T cell-mediated autoimmune diseases.

Animals↗
PubMed1988

Influence of estrogen receptor status on dietary risk factors for breast cancer.

It has been suggested that the relation between diet and breast cancer may depend on estrogen receptor (ER) status. We examined the responses to a self-administered questionnaire on frequency of consumption of various foods by 493 women with breast cancer (160 with ER-negative tumours and 333 with ER-positive tumours) and 527 controls whose menopausal status was known. Analysis of the reported consumption of foods selected for their fat or carotene content showed no clear distinction in dietary factors between the ER-negative and ER-positive groups. Frequent consumption of meat fats generally increased the risk of both ER-negative and ER-positive tumours; there were no clear trends in risk associated with vegetable consumption for either ER group. Fish was the only item affecting the risk for ER-negative and ER-positive tumours differently, frequent consumption reducing the risk for the former (p = 0.02). The results do not support the hypothesis that ER status influences the relation between dietary fat consumption and risk of breast cancer.

Adult↗
PubMed1987

The prognostic significance of psychosocial factors in women with breast cancer.

One hundred and thirty three recently diagnosed breast cancer patients completed a self-administered questionnaire which measured 16 psychosocial variables. After 4 years, three variables (expressive activities at home, extroversion, low anger) were significant prognostic factors for overall survival independent of clinical and other psychosocial factors; likewise three variables (expressive activities at home, expressive activities away from home, low cognitive disturbance) were significant independent prognostic factors for disease-free survival. These findings support the prognostic importance of the social emotional network.

Adult↗
PubMed1986

Relationship between risk factors for breast cancer and hormonal status.

A total of 512 breast cancer patients and 540 controls were compared to examine the risk factors for different categories of breast cancer as defined by age, menopausal status and estrogen receptor (ER) tumor status. Significant differences were found by menopausal status, for age at first birth and age at menarche for all women, and for age at first birth and family history for women between 45 and 54 years old. No significant differences were found with ER status alone; however there was a significant difference between ER status and body weight in premenopausal women; the above significant differences with menopausal status were not found when stratified by ER tumour status. These findings support the hypothesis for aetiological differences for pre- and postmenopausal breast cancer and suggest that ER tumour status may influence the risk associated with body weight.

Adult↗
PubMed1986

Childhood and recent eating patterns and risk of breast cancer.

A case-control study was done to examine the relationship between childhood and recent eating practices and risk of breast cancer. Eight hundred forty-six cases and 862 controls returned questionnaires indicating their menopausal status. In premenopausal women, breast cancer risk was increased with recent consumption of foods high in fat content (gravy, beef, pork) and reduced with foods low in fat content (fish); in postmenopausal women, risk was increased with pork consumption only. Regarding carotene sources, risk was reduced with carrot consumption in postmenopausal women only. Similar trends in risk were not found for childhood eating practices. Body weight influenced the breast cancer risk differently for pre- and postmenopausal women: Heavier weight in childhood and teens reduced the risk of premenopausal breast cancer, and heavier weight in adulthood increased the risk of postmenopausal breast cancer. We conclude that fat consumption is associated with breast cancer, especially in premenopausal women.

Adult↗