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Biomedical subjects

Louis W C Chow

Publications and source records attributed to Louis W C Chow.

At least 19 recordsLinked to original sources
PubMed2025

Neoadjuvant palbociclib in women with operable, hormone receptor-positive breast cancer.

The addition of a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor to endocrine therapy augments biological response in breast cancer. This phase III randomized, double-blind study evaluated the efficacy of adding palbociclib to neoadjuvant endocrine therapy (NET) for operable, hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Patients randomly received 16 weeks of endocrine therapy (letrozole for postmenopausal and tamoxifen plus ovarian function suppression for pre-/perimenopausal patients) plus palbociclib or placebo. The co-primary endpoints included preoperative endocrine prognostic index (PEPI) score and EndoPredict (EPclin) risk score according to the gatekeeping procedure. Of 141 randomized patients, 130 completed the treatment with surgical samples evaluable for endpoints in 126 patients. The proportion of patients with a low, moderate, and high PEPI score was 15.2, 50.0, and 34.8% in the palbociclib arm and 13.3, 55.0, and 31.7% in the placebo arm, respectively, with no statistical difference (one-sided P = 0.563). Statistical analysis was not performed on EPclin risk score. No new safety signals were reported. Permanent treatment discontinuation by adverse events was reported for seven (9.7%) and zero patients in the palbociclib and placebo arms, respectively. In conclusion, the addition of palbociclib to NET did not improve the efficacy. ClinicalTrials.gov NCT03969121.

Humans↗
PubMed2006

Clinical experience with docetaxel for Chinese breast cancer patients: hematological toxicity profiles.

BACKGROUND: Asians are generally regarded to tolerate cytotoxic drugs less well than their Caucasian counterpart. A substantial proportion of patients receive suboptimal doses of chemotherapy for fear of severe toxicity. This retrospective study aims to evaluate the adverse events, especially hematological, of docetaxel in Chinese patients with breast cancer. PATIENTS AND METHODS: Fifty-nine patients, age ranged from 33 to 70 (median=47) years, were assigned to receive 3 to 6 (median=4) cycles of Docetaxel 100 mg/m2 every 21 days as neoadjuvant (n=3), adjuvant (n=26), neoadjuvant plus adjuvant (n=3), or active therapy for metastatic or relapsed breast cancer (n=27). RESULTS: A total of 56 (95%) patients completed the assigned whole regimen and only 3 (5%) patients discontinued due to either poor tolerance to the drug's side effects or worsening of disease leading to death. On average, the received dose intensity (RDI) was 0.86 for docetaxel 100 mg/m2 in this study. Among all the clinical adverse events, hematological toxicities were not excessively higher. Of the total 59 patients, major adverse events of all grades were leukopenia (22%), neutropenia (20%), fever (19%), and febrile neutropenia (14%). Only 12% and 14% of patients experienced grade 3 or 4 leukopenia and neutropenia, respectively. CONCLUSION: In view of the increasing breast cancer incidence and the acceptable toxicity profile of docetaxel among Chinese patients, a dosage of 100 mg/m2 can be recommended for use among Asians.

Adult↗
PubMed2006

Possible predictive markers related to micro-metastasis in breast cancer patients.

Despite significant advances in micro-metastasis detection methods, little is known about the relationship between micro-metastasis and primary tumors. The purpose of this study was to assess the ability of expression of the breast cancer-related markers, HER-2/neu, COX-2, VEGF and PDGF-B, as a predictor for micro-metastasis. As destination sites for micro-metastasis, we examined the peripheral blood (BD), bone marrow (BM) and sentinel lymph node (SLN) from 53 breast cancer patients. Protein and gene expression of the markers at the primary site were determined by immunohistochemistry (IHC) and quantitative RT-PCR. BD and BM samples were processed using magnetic-activated cell separation and immunocytochemistry. SLNs were examined by hematoxylin and eosin (H&E) staining and IHC. The percentages of patients with micro-metastasis were 24.5% in BD, 56.6% in BM, 26.4% in SLN by H&E and 41.5% in SLN by IHC. COX-2 gene amplification was significantly associated with SLN micro-metastasis by H&E (P=0.03). Overexpression of HER-2/neu predicts the presence of SLN micro-metastasis as detected by H&E (P=0.005) and COX-2 overexpression predicts the presence of micro-metastasis in BM (P=0.005) and SLN by H&E (P<0.001) and IHC (P<0.001). Similarly, PDGF-B overexpression predicts micro-metastasis in BD (P=0.002), BM (P=0.003) and SLN by H&E (P=0.017), whereas VEGF overexpression predicts only the presence of SLN micro-metastasis by IHC (P=0.001). Our results indicate the possible value of using these markers to predict the risk of micro-metastasis in breast cancer.

Biomarkers, Tumor↗
PubMed2005

The cell cycle checkpoint gene Rad9 is a novel oncogene activated by 11q13 amplification and DNA methylation in breast cancer.

Human Rad9 (hRad9), a structural homologue of yeast Schizosaccharomyces pombe rad9, is involved in cell cycle checkpoints and apoptosis. hRad9 can serve as a corepressor of androgen receptor in prostate cancer cells, but little is known about its role in the development of breast or other cancers. In the present study, semiquantitative reverse transcription-PCR showed that Rad9 mRNA levels were up-regulated in 52.1% (25 of 48) of breast tumors, and this up-regulation correlated with tumor size (P = 0.037) and local recurrence (P = 0.033). Overexpression of Rad9 mRNA was partly due to an increase in Rad9 gene number as measured by quantitative PCR. In other breast tumors with Rad9 mRNA overexpression but without increase in gene number, there was differential methylation of two putative Sp1/3 binding sites within the first and second introns of the Rad9 gene, which was similarly found in MCF-7 breast cancer cell line with increased Rad9 mRNA. Silencing Rad9 expression by RNA interference in MCF-7 cell line inhibited its proliferation in vitro. Promoter assays indicated that the Sp1/3 site in intron 2 may act as a silencer. In vivo binding of Sp3 to intron 2 was shown by chromatin immunoprecipitation assays. Treatment of MCF-7 cell line with 5'-aza-2'-deoxycytidine reduced Rad9 mRNA expression and also increased binding of Sp3 to the demethylated intron 2 region. Collectively, these findings suggest that Rad9 is a novel oncogene candidate activated by 11q13 amplification and DNA hypermethylation in breast cancer and may play a role in tumor proliferation and local invasion.

Azacitidine↗
PubMed2005

Phase II study of an 'all-oral' regimen of capecitabine, idarubicin and cyclophosphamide for metastatic breast cancer--safety, efficacy and quality of life.

OBJECTIVE: Patients with metastatic breast cancer (MBC) generally have a poor prognosis. Many of these patients have a good performance status. A new all-oral regimen (XIC) was evaluated in a phase II trial. The impact of the regimen on the safety and efficacy of the drug, as well as quality of life (QOL) of the patients was assessed. PATIENTS AND METHODS: From September 2000 to September 2001, informed consent was obtained from 20 heavily pretreated women with MBC. They were placed on a 6-week cycle regimen comprising capecitabine (X; 2,000 mg/m2/day in two divided doses for 2 weeks then 1 week rest), idarubicin (I; 10 mg/m2/day, days 1, 3 and 5) and cyclophosphamide (C; 100 mg/m2/day for 2 weeks then 1 week rest). RESULTS: Toxicities were generally tolerable. One patient had grade III neutropenia, which was reversible on cessation of treatment. One patient (5%) had a complete response and 4 patients (20%) achieved partial responses, yielding an overall response rate of 25%. Eight patients (40%) had stable disease. Median time to disease progression and median survival time were 13.4 and 23.7 months, respectively. Global and physical EORTC QLQ-30 scores showed no significant decrease in QOL. CONCLUSION: This is a small-scale study. XIC was generally well tolerated and favoured by the patients. This moderately active and convenient 'all-oral' regimen deserves clinical trials at a wider scale.

Administration, Oral↗
PubMed2005

Trastuzumab: updates and future issues.

Trastuzumab has had an enormous impact on the clinical management of breast cancer: the survival of Her-2-positive metastatic breast cancer patients has improved significantly and tumor Her-2 status has been built into the decision-making tree for primary breast cancer patients. Several pioneering studies have shown that trastuzumab-combined chemotherapy elicits high levels of pathological complete response in the neoadjuvant setting. Currently, therefore, a more precise understanding of the mechanisms of therapeutic response is needed so that trastuzumab-based therapies can be optimized more individually. It might also be important to investigate, with greater depth, the interaction between the Her-axis and the hormone-axis. This short review describes and discusses these topics.

Antibodies, Monoclonal↗
PubMed2005

Association between body mass index and risk of formation of breast cancer in Chinese women.

OBJECTIVE: To analyse the association between body mass index (BMI) and breast cancer risk among Chinese women in Hong Kong. METHODS: We conducted a population-based case control study of breast cancer in June 2002. Standardized questionnaires concerning BMI and other anthropometric data were completed by patients at the Queen Mary Hospital (QMH). The cases were 198 women aged 24-85 years who had documented breast cancer in 1995-2000 by triple assessment criteria, and the controls were 353 women who were followed up at QMH for benign breast disease after breast cancer had been excluded by triple assessment. The controls were frequency-matched to the cases by age. RESULTS: BMI at diagnosis was positively correlated with the risk of breast cancer among postmenopausal women (p < 0.001 for trend). Also, when compared with women with a low BMI (< 19), women with a BMI of 23-27 and 27-31 had a 1.73-fold (95% confidence interval, CI, 1.04-2.86) and 2.06-fold (95% CI, 1.08-3.93) increased risk of breast cancer, respectively, after adjustment for non-anthropometric risk factors. BMI at diagnosis, however, was not related to the risk of breast cancer among premenopausal women. The odds ratios for premenopausal women with a BMI of 23-27 and 27-31 were 1.5 (95% CI, 0.82-2.71) and 1.32 (95% CI, 0.39-4.43), respectively. Furthermore, present BMI and BMI 5 years before diagnosis were poorly associated with breast cancer risk among both pre- and postmenopausal women. CONCLUSION: Weight control in obese women may be an effective measure for breast cancer prevention in postmenopausal women.

Adult↗
PubMed2005

Thymidine phosphorylase (platelet-derived endothelial-cell growth factor) in cancer biology and treatment.

Thymidine phosphorylase (TP) is often induced in the tumour microenvironment by physiological and chemical stress. Its induction protects cells from apoptosis and helps cell survival by stimulating nucleoside metabolism and angiogenesis. Chemotherapy often upregulates TP, which acts in cell rescue; this result indicates that TP is a crucial therapeutic target. Clinical trials for metastatic diseases have shown that TP-targeting chemotherapy with fluorouracil derivatives greatly improves the effectiveness of conventional chemotherapy for not only response but also prognosis. This new idea, the improvement of TP-inducible therapy with TP-targeting therapy, should be further investigated for early disease states, and inhibitors of TP warrant extensive investigation.

Apoptosis↗
PubMed2004

Production of matrix metalloproteinases in specific subpopulations of human-patient breast cancer invading in three dimensional culture system.

This article aims at investigating the effect of production of matrix metalloproteinases (MMP) in human breast cancer tissues by means of three dimensional culture system. Thirty-nine tumour samples were taken from breast cancer patients. The tumour blocks were cultured on sponge gel using the three dimensional culture system. Breast cancer cells began shedding into the culture medium after 24 hours of culture. The cells were stained with trypan blue dye to assess viability on days 2, 4, 6 and 8. The culture medium was collected at these time points and tested for matrix metalloproteinases (MMP) 1,2,3 and 9 activities. There was a progressive increase in migration of cancer cells into the gel and culture medium from day 2 to day 8 and the interval difference was statistically significant (F ratio=4.06; p=0.008). The levels of all the MMPs tested were also significantly raised (P<0.05 for all the MMPs tested). When the levels of MMPs were correlated with the metabolic activities in the gel, medium and tumour block, cells in block show no correlation whereas cells in gel correlated significantly with MMP-1 and MMP-3. Cancer cells in the culture medium correlated with MMP-9. In conclusion, there is a progressive migration of cancer cells outside the tumour block. The migration into the gel and culture medium is associated with progressive and differential production of MMPs. It is likely that the three dimensional culture model assists in the selection of different subpopulations of cancer cells with different invasion properties as exemplified by the differential production of MMP.

Adenosine Triphosphate↗
PubMed2004

Arimidex inhibition on proliferation of human breast solid tumors measured by ATP bioluminescence.

To determine the degree of Arimidex (Anastrozole) inhibition on proliferation of human breast solid tumors in vitro by ATP bioluminescence assay. Breast cancer solid tumors with different hormone receptors and grading were collected from 38 Chinese women with invasive breast cancers. Tumors were treated with three concentrations of Arimidex (1.5 mM, 15 mM and 150 mM). ATP bioluminescence assay was used to measure the metabolic rate in order to determine the degree of inhibition of Arimidex on the breast cancer tumors by comparing to the untreated tumors. 15 mM Arimidex shows greatest inhibitory effect on the proliferation of solid tumors with ER-postive/PR-positive. It can also inhibit the growth of metastatic tumors and tumors with HER-2/neu expression. It shows greater inhibitory effect in lower grading of tumors then higher. Arimidex may effectively inhibit the growth of breast tumors in in vitro system by inhibiting aromatase and block estrogen dependent tumor growth.

Adenosine Triphosphatases↗
PubMed2004

The inhibitory effect of a herbal formula comprising ginseng and carthamus tinctorius on breast cancer.

A compound (Zhu-xiang) from herbal extracts containing ginseng and carthamus tinctorius was used to treat the MDA-MB-231 breast cancer cell and normal human mammary gland cell lines. The inhibition of cell proliferation by Zhu-xiang, epirubicin, 5-fluorouracil and cyclophosphamide was determined by WST-1 assays. The apoptotic effect was studied by flow cytometry analysis of DNA strand breaks and ApopTag Peroxidase In Situ Apoptosis kit by the TUNEL assay. The proliferation index as well as cell cycle progression were also evaluated by flow cytometry using Ki-67 and propidium iodide respectively as markers. The Zhu-xiang showed significantly inhibition in cell proliferation and the inhibition was dose dependent. The inhibitory effect of Zhu-xiang was significantly greater than commonly used cytotoxic drugs. The inhibitory effect is a result of the induction of apoptosis, which is concentration- and time-dependent. DNA histograms indicate that the compound causes accumulation of cells mainly in the S phase. The viability of cells in breast solid tumours was measured by ATP bioluminescence assay to determine the drug-induced cytotoxicity of Zhu-xiang. The three different concentrations of Zhu-xiang all exhibited the ability to inhibit proliferation in solid tumour. Zhu-xiang could be a useful anti-cancer compound against breast cancer.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Her2/neu expression predicts the response to antiaromatase neoadjuvant therapy in primary breast cancer: subgroup analysis from celecoxib antiaromatase neoadjuvant trial.

PURPOSE: Many studies suggest that Her2/neu play an important role in neoadjuvant endocrine therapy. This study aimed to determine whether the level of Her2/neu expression in advanced breast cancer changes after antiaromatase neoadjuvant treatment, as well as to identify the relationship between Her2/neu expression and response to this kind of therapy. EXPERIMENTAL DESIGN: Thirty-six postmenopausal patients with hormonal receptor-positive primary breast cancer were included in a study of three monthly cycles of neoadjuvant endocrine therapy with either Aromasin (25 mg daily) or Femara (2.5 mg daily). Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for Her2/neu were conducted both on pretreatment biopsies and surgical tumors. RESULTS: Using IHC, 5 of 36 (13.9%) of the patients had a Her2/neu overexpression after treatment, as compared with 16 of 36 (44.4%) before. Meanwhile, there was no change in 21 (58.3%) patients, and through FISH, there was a change from amplification to no amplification in 15 (41.7%) patients. The response rate to the treatment was 75% for Her2/neu (+) tumors and 35% for Her2/neu (-) tumors (P = 0.017) while FISH was performed. The response rate was also significantly affected by the decrease in Her2/neu status after the treatment, with 73% of the tumors showing decreased Her2/neu expression and with 38% of the tumors showing no change of Her2/neu expression (P = 0.037). CONCLUSIONS: Using both IHC and FISH, advanced breast cancers show statistical evidence of decreasing incidence of Her2/neu expression after antiaromatase neoadjuvant treatment. Our data also suggest that Her2/neu expression and its change during the treatment might be predictive markers for this kind of therapy.

Aged↗
PubMed2004

Sentinel lymph node biopsy or detection of micrometastasis in bone marrow: which might be an alternative to axillary lymph node dissection in breast cancer patients?

Axillary lymph node status has limited prognostic significance in breast cancer patients and much improvement can be made. Sentinel lymph node biopsy is emerging as an alternative to axillary lymph node dissection for staging, but its prognostic relevance is still uncertain. Detection of micrometastases in sentinel nodes and bone marrow may provide more information, but the clinical significance still needs to be confirmed by ongoing large trials. In this review, we focus on the possibility of sentinel lymph node biopsy or detection of bone marrow micrometastasis replacing traditional axillary lymph node dissection.

Axilla↗
PubMed2004

Sentinel lymph node technique for breast cancer: radiation safety issues.

The radiation safety issues in the application of radioguided sentinel lymph node (SLN) biopsy are discussed, particularly the effective dose (ED) for patients undergoing lymphoscintigraphy by taking into account both the internal emission and the external transmission dose. The quantitative result can be compared with other common radiological examinations. Whole body and finger doses of surgical and pathology staff were determined by direct measurement using high-sensitivity thermoluminescent dosimeters (TLDs) and compared with the annual dose limits recommended by the International Commission on Radiological Protection (ICRP). These dosimetric observations for personnel also provide reference information to implement guidelines for the safe handling, storage, and transport of radioactive specimens at all stages of the radioguided surgery effort in order to maintain good work practices while dealing with unsealed radioactive substances.

Breast Neoplasms↗
PubMed2004

Radix bupleuri containing compound (KY88 liver-livo) induces apoptosis and production of interleukin-4 and tumor necrosis factor-alpha in liver cancer cells in vitro.

Hepatocellular carcinoma is an important health problem in Asia. A blend of herbal extracts containing radix bupleuri (KY88) was tested for its effects on liver cancer cells. A hepatocellular carcinoma cell line (HB8064) was cultured with methanol extract of KY88. We were able to produce a dose-dependent inhibition of cancer cell proliferation. At IC50 and IC100, KY88 induces a DNA ladder pattern, indicating the presence of apoptosis. We also checked the changes of the levels of interleukin (IL)-2, -4 and -6, interferon (INF)-gamma and tumor necrosis factor (TNF)-alpha by ELISA kits. After 24 hours of culture, there was activation of IL-2 and -4 and TNF-alpha. However, significant changes were observed only for IL-4 and TNF-alpha. Therefore, we concluded that KY88 is able to induce apoptosis, which may be regulated through changes in IL-4 and TNF-alpha.

Apoptosis↗
PubMed2003

A rat cell line derived from DMBA-induced mammary carcinoma.

A new cell line, designated UHKBR-01, was successfully established from a 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumour. DMBA was administered orally at a dose of 4 mg/ml per rat on the first day of the experiment and thereafter at weekly intervals of same dosage, until the rats have reached a weight of around 150-200 g. The tumours grew rapidly after the injection, and were transplanted into nude mice one the harvest size (2.5 x 2 x 1 mm(3)) was reached, it was transplanted onto nude mice. We have developed a cell line from a portion of the DMBA-induced carcinoma of the nude mice. The UHKBR-01 cell exhibited a slow increase in growth rate during the time of culture and was highly tumourigenic in nude mice. The cells have been grown in culture for over 40 passages. Characterization of the cell line was performed. This included morphology by light and transmission electron microscopy, karyotype, growth rate, tumour antigen expression and xenograft implantation into nude mice. These cells exhibit ultrastructural and immunohistochemical features of epithelial cells of mammary origin. The above analyses also demonstrated that UHKBR-01 cells were oestrogen- and progesterone-receptor positive, in likeness to other established breast cancer cell lines such as MDA-MB-231 and MCF-7. The cell line grows as monolayers of oval-shaped cells with large folded nuclei accompanied by a rich supply of mitochondria. This report describes the first in vitro cell line from transplantable DMBA-induced mammary carcinoma of nude mice, which presents unique characteristics that may prove to be a good experimental model for investigating breast cancer biology.

9,10-Dimethyl-1,2-benzanthracene↗