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Bing Lam,
Sui Y Lam, Maria P Wong,
Clara G C Ooi,
Daniel Y T Fong,
David C L Lam,
Agnes Y K Lai,
Cheuk-Ming Tam,
Clara B Y Pang,
Mary S M Ip,
Wah-Kit Lam
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ABSTRACT: The prognosis of early stage lung cancer was superior to that of late stages. We hypothesize that by using sputum cytology as the first screening method followed by autofluorescence bronchoscopy could detect early stage lung cancer in the central airway.
During 18-month recruitment period, subjects at high risk for lung cancer (ever smoker accumulated more than 20 pack-year and above 40 years) followed up at Chest Clinics were invited to submit sputum for cytological examination. Subjects with sputum atypia were invited to have bronchoscopy, and CT thorax. After a mean follow-up of 39+/-14 months, the characteristics of lung cancers detected in the group with sputum atypia and the group with normal sputum at baseline were assessed.
181 subjects submitted sputum and primary lung cancer were diagnosed in 13. 46.2% of the lung cancers were in early stages. Bronchoscopy were performed in 85, and seven were confirmed to have lung cancer (six were in early stages). 81 had CT done and 92.6% had radiological abnormalities, though three lung cancers (all stage 0) were missed by CT. Five more primary lung cancers were diagnosed during the follow-up period: one in sputum atypia group and the other four (three were advanced adenocarcinoma) in normal sputum group. The overall sensitivity of sputum cytology in detecting lung cancer was 71.4% for all histology and 100% for squamous cell lung cancer.
Sputum cytology examination followed by bronchoscopy was a practical way of detecting early stage lung cancer in central airway.
Lung cancer (Amsterdam, Netherlands) 12/2008; 64(3):289-94. · 3.14 Impact Factor
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ABSTRACT: This single-center, phase II study assessed the safety/tolerability and initial efficacy of gefitinib in patients with nasopharyngeal carcinoma (NPC) pretreated with platinum-based chemotherapy.
Patients with recurrent and metastatic NPC who had treatment failure with at least 2 lines of chemotherapy including platinum were given gefitinib at a fixed dose of 250 mg daily. Treatment was continued until the patient experienced unacceptable side effects or disease progression.
Nineteen patients were enrolled, having had treatment failure with a median of 2 chemotherapy regimens. Treatment was well tolerated, and only grades 1 to 2 adverse events were observed. None of the patients achieved partial or complete response. Median time-to-progression was 4 months, and median overall survival was 16 months.
Gefitinib was well tolerated, but the response rate was poor in this heavily pretreated study population, and its use in NPC is not recommended outside the context of clinical trial.
Head & Neck 08/2008; 30(7):863-7. · 2.40 Impact Factor
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Matthew K Wong, Maria P Wong,
David C Lam,
Alan Sihoe,
L C Cheng,
B Lam,
Mary S Ip,
T Nakajima,
K Yasufuku,
W K Lam,
James C Ho
[show abstract]
[hide abstract]
ABSTRACT: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has recently been shown to be accurate in diagnosis and staging of mediastinal lymph node metastases. We report a case of squamous cell carcinoma diagnosed by endobronchial biopsy with concomitant contralateral hilar lymph node metastasis from small cell carcinoma being confirmed by EBUS-TBNA. The diagnosis of synchronous primary lung cancers in this case, which altered the treatment strategy, would not be made if pathological staging of intrathoracic lymph node was not pursued. The unique role of EBUS-TBNA in diagnosis of hilar lymphadenopathy was underscored. The potential pitfall of missing synchronous lung tumour if the diagnosis is based either on sampling from intrathoracic lymph node or from endobronchial lesion alone is discussed.
Lung Cancer 07/2008; 63(1):154-7. · 3.43 Impact Factor
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David Chi-Leung Lam,
Luc Girard,
Ruben Ramirez,
Wing-Shun Chau,
Wai-sing Suen,
Shelley Sheridan,
Vicky P C Tin,
Lap-ping Chung, Maria P Wong,
Jerry W Shay,
Adi F Gazdar,
Wah-kit Lam,
John D Minna
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ABSTRACT: Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChR) on bronchial epithelial cells, can regulate cellular proliferation and apoptosis via activating the Akt pathway. Delineation of nAChR subtypes in non-small-cell lung cancers (NSCLC) may provide information for prevention or therapeutic targeting. Expression of nAChR subunit genes in 66 resected primary NSCLCs, 7 histologically non-involved lung tissues, 13 NSCLC cell lines, and 6 human bronchial epithelial cell lines (HBEC) was analyzed with quantitative PCR and microarray analysis. Five nonmalignant HBECs were exposed to nicotine in vitro to study the variation of nAChR subunit gene expression with nicotine exposure and removal. NSCLCs from nonsmokers showed higher expression of nAChR alpha6 (P < 0.001) and beta3 (P = 0.007) subunit genes than those from smokers, adjusted for gender. In addition, nAChR alpha4 (P < 0.001) and beta4 (P = 0.029) subunit gene expression showed significant difference between NSCLCs and normal lung. Using Affymetrix GeneChip U133 Sets, 65 differentially expressed genes associated with NSCLC nonsmoking nAChR alpha6beta3 phenotype were identified, which gave high sensitivity and specificity of prediction. nAChR alpha1, alpha5, and alpha7 showed significant reversible changes in expression levels in HBECs upon nicotine exposure. We conclude that between NSCLCs from smokers and nonsmokers, different nAChR subunit gene expression patterns were found, and a 65-gene expression signature was associated with nonsmoking nAChR alpha6beta3 expression. Finally, nicotine exposure in HBECs resulted in reversible differences in nAChR subunit gene expression. These results further implicate nicotine in bronchial carcinogenesis and suggest targeting nAChRs for prevention and therapy in lung cancer.
Cancer Research 05/2007; 67(10):4638-47. · 7.86 Impact Factor
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ABSTRACT: Bronchogenic adenocarcinoma is the predominant histologic subtype of lung cancer, which ranks top in the cancer mortality in both men and women. Female nonsmokers and adenocarcinoma have emerged as a distinct combination in patients with lung cancer in recent decades. Lung cancer cell lines established from patients with known clinical characteristics such as gender and smoking habit would be useful for future research on lung cancer.
Four new lung adenocarcinoma cell lines (HKULC 1-4) were established from Chinese patients with primary lung adenocarcinomas and with different clinical characteristics with respect to age, gender, smoking habits, tumor staging, and previous therapy. They were characterized by immunohistochemical and growth kinetic studies, tests for tumorigenicity in nude mice, epidermal growth factor receptor (EGFR) gene mutation analysis, and in situ hybridization, and gene expression profiling with Affymetrix GeneChip HG-U133A.
The newly established HKULC lung adenocarcinoma cell lines were maintained for over 70 passages and demonstrated morphologic and immunohistochemical features and growth kinetics of tumor cell lines. One of the four HKULC cell lines, HKULC 3 (derived from a female nonsmoking patient with lung adenocarcinoma), was found to have a deletion at exon 19 of the EGFR gene. EGFR in situ hybridization showed no EGFR gene amplification in these cell lines. HKULC 1 and 4 formed tumor xenografts after inoculation in nude mice. A list of 71 genes that were differentially expressed or showing class predictive significance was identified. These genes included putative tumor suppressor genes (DKK3, SERPINF1, CDH11, DSC3, and KLF6), genes involved in or related to the EGFR pathways (ERBB3, MUC1, VAV1), genes involved in regulation of cell cycle and proliferation (CDKN1A and CDKN2A), a putative oncogene (EEF1A2), and a gene related to metastasis (MTSS1).
Four new lung adenocarcinoma cell lines were established from patients with different clinical characteristics. These characterized cell lines and their gene expression profiles will provide resources for studies of lung cancer biology and in vitro chemotherapeutic drug study.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2006; 1(9):932-42. · 4.55 Impact Factor
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ABSTRACT: Lymphoepithelioma-like carcinoma (LELC) of the lung was first reported in 1987. In the past two decades, there have been just more than 150 cases reported in the literature. This uncommon but distinct form of non-small cell lung carcinoma has a predilection for young non-smoking Asians, without gender distinction. Histologically, it is indistinguishable from undifferentiated nasopharyngeal carcinoma. The carcinogenic role of latent Epstein-Barr virus infection in causing LELC of the lung has been evident almost exclusively in Asians compared with Caucasians. Among the reported cases, more than half were in early resectable stages (I or II) and there was a tendency for peribronchovascular spread with vascular encasement in advanced diseases. In order to establish the diagnosis of LELC of the lung, both nasopharyngeal carcinoma and lymphoma have to be excluded by endoscopic biopsy (with or without magnetic resonance imaging of the nasopharynx) and immunohistochemical staining of the biopsy samples. The mainstay of treatment for early-stage disease is curative surgical resection, whereas multimodality treatment (surgery, chemotherapy, radiotherapy) has been adopted in advanced or metastatic diseases. The overall survival is more favourable in LELC of the lung compared with non-LELC type of non-small cell lung carcinoma. Future collaborative studies especially on optimizing treatment for this uncommon malignancy are clearly warranted.
Respirology 10/2006; 11(5):539-45. · 2.42 Impact Factor
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Issan Yee San Tam,
Lap Ping Chung,
Wai Sing Suen,
Elaine Wang,
May C M Wong,
Kok Keung Ho,
Wah Kit Lam,
Shui Wah Chiu,
Luc Girard,
John D Minna,
Adi F Gazdar, Maria P Wong
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ABSTRACT: This study evaluated the mutational profile of epidermal growth factor receptor (EGFR) and KRAS in non-small cell lung cancers in Hong Kong and determined their relation with smoking history and other clinicopathologic features.
Mutational profile of exons 18 to 21 of EGFR and codons 12, 13, and 61 of KRAS were determined in 215 adenocarcinomas, 15 squamous cell (SCC), and 11 EBV-associated lymphoepithelioma-like carcinomas (LELC).
EGFR mutations were prevalent in adenocarcinomas (115 of 215), uncommon in LELC (1 of 11), and not found in SCC (P < 0.001). Among adenocarcinomas, mutations were associated with nonsmokers (83 of 111; P < 0.001), female gender (87 of 131; P < 0.001), and well-differentiated (55 of 86) compared with poorly differentiated (11 of 41) tumors (P < 0.001). Decreasing mutation rates with increasing direct tobacco exposure was observed, with 74.8% (83 of 111) in nonsmokers, 61.1% (11 of 18) in passive, 35.7% (10 of 28) in previous, and 19.0% (11 of 58) in current smokers. There were 53% amino acid substitutions, 43% in-frame deletions, and 4% insertions. Complex patterns with 13% double mutations, including five novel substitutions, were observed. For KRAS, mutations occurred in adenocarcinoma only (21 of 215) and were associated with smokers (11 of 58; P = 0.003), men (14 of 84; P = 0.009) and poorly differentiated (7 of 41) compared with well-differentiated (4 of 86) tumors (P = 0.037). EGFR and KRAS mutations occurred in mutually exclusive tumors. Regression analysis showed smoking history was the significant determinant for both mutations, whereas gender was a confounding factor.
This study shows EGFR mutations are prevalent in lung adenocarcinoma and suggests that it plays an increasing oncogenic role with decreasing direct tobacco damage.
Clinical Cancer Research 04/2006; 12(5):1647-53. · 7.74 Impact Factor
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Yee Leng Yap,
David C L Lam,
Girard Luc,
Xue Wu Zhang,
David Hernandez,
Robin Gras,
Elaine Wang,
S W Chiu,
Lap Ping Chung,
W K Lam,
David K Smith,
John D Minna,
Antoine Danchin, Maria P Wong
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ABSTRACT: Gene transcription in a set of 49 human primary lung adenocarcinomas and 9 normal lung tissue samples was examined using Affymetrix GeneChip technology. A total of 3442 genes, called the set M AD, were found to be either up- or down-regulated by at least 2-fold between the two phenotypes. Genes assigned to a particular gene ontology term were found, in many cases, to be significantly unevenly distributed between the genes in and outside M AD. Terms that were overrepresented in M AD included functions directly implicated in the cancer cell metabolism. Based on their functional roles and expression profiles, genes in M AD were grouped into likely co-regulated gene sets. Highly conserved sequences in the 5 kb region upstream of the genes in these sets were identified with the motif discovery tool, MoDEL. Potential oncogenic transcription factors and their corresponding binding sites were identified in these conserved regions using the TRANSFAC 8.3 database. Several of the transcription factors identified in this study have been shown elsewhere to be involved in oncogenic processes. This study searched beyond phenotypic gene expression profiles in cancer cells, in order to identify the more important regulatory transcription factors that caused these aberrations in gene expression.
Nucleic Acids Research 02/2005; 33(1):409-21. · 8.03 Impact Factor
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ABSTRACT: Lymphangioleiomyomatosis (LAM) is a rare parenchymal lung disease, which affects young women of childbearing age and is characterized pathologically by proliferation of interstitial smooth muscle and formation of cysts in the lung. While LAM is usually predominantly a respiratory disorder, it can also initially involve other extrapulmonary organs. We report the case of a 35-year-old Chinese woman, who presented with a 4-week history of left thigh swelling which was found to be secondary to compression of pelvic veins by a mass lesion. The latter was found histologically to show LAM. Despite the patient being asymptomatic and displaying normal lung function, a thoracic high resolution CT scan showed typical features of early LAM. This case further illustrates that LAM can have multisystem involvement, and demonstrates the importance of being aware of the diagnosis in cases presenting with extrapulmonary manifestation, in order that patients are diagnosed and managed appropriately.
Respirology 01/2004; 8(4):544-7. · 2.42 Impact Factor
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ABSTRACT: Lung carcinoma is a common malignancy, and tobacco carcinogenesis is the major cause. Studies on individual genes or loci have suggested, that in tumors from nonsmokers, different genetic alterations are present compared with tumors from smokers. It is possible that distinct genetic pathways may be involved. However, the targets remain largely unknown; and, to the authors' knowledge, molecular cytogenetics studies on lung carcinomas from nonsmokers have not been reported.
Comparative genomic hybridization (CGH) analysis was performed on primary lung adenocarcinoma samples from 32 patients who never smoked to identify loci of frequent aberrations.
Different extents of aberration were found in 31 of the 32 samples studied. The most frequently altered locus was gain of 16p (59% of samples) followed by gain of 20q (44% of samples), with the minimal overlapping regions at 16p13.1-p13.2 and 20q13.2, respectively. Other over-represented loci with > 30% frequency were observed at 5p (34% of samples), 7p (41% of samples), 8q (31% of samples), 17q (34% of samples), and 19q (34% of samples); and high-level DNA amplifications were detected at 1q, 7p, 12q, 19q, and 20q. DNA under-representation was observed less commonly and included 8p (28% of samples), 9p (22% of samples), 13q (28% of samples), and 18q (38% of samples).
The current study identified targets of frequent genetic aberration in primary adenocarcinomas from nonsmokers. Compared with reported CGH findings in the literature, the current findings suggest that DNA gain at 16p is the distinct aberration involved in these tumors. Other frequently altered loci involve commonly reported oncogenic and tumor suppressor loci, suggesting an overlap with the genetic pathways of tobacco-induced lung carcinogenesis.
Cancer 04/2003; 97(5):1263-70. · 4.77 Impact Factor
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Maria P. Wong M.D,
Lai-Fan Fung M.Sc,
Elaine Wang M.D,
Wing-Shun Chow M.D,
Shui-Wah Chiu M.D,
Wah-Kit Lam M.D,
Kwok-Keung Ho M.D,
Edmond S. K. Ma M.D,
Thomas S. K. Wan Ph.D,
Lap-Ping Chung D.Phil, Maria P. Wong,
Lai‐Fan Fung,
Elaine Wang,
Wing‐Shun Chow,
Shui‐Wah Chiu,
Wah‐Kit Lam,
Kwok‐Keung Ho,
Edmond S. K. Ma,
Thomas S. K. Wan,
Lap‐Ping Chung
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ABSTRACT: BACKGROUND
Lung carcinoma is a common malignancy, and tobacco carcinogenesis is the major cause. Studies on individual genes or loci have suggested, that in tumors from nonsmokers, different genetic alterations are present compared with tumors from smokers. It is possible that distinct genetic pathways may be involved. However, the targets remain largely unknown; and, to the authors' knowledge, molecular cytogenetics studies on lung carcinomas from nonsmokers have not been reported.METHODS
Comparative genomic hybridization (CGH) analysis was performed on primary lung adenocarcinoma samples from 32 patients who never smoked to identify loci of frequent aberrations.RESULTSDifferent extents of aberration were found in 31 of the 32 samples studied. The most frequently altered locus was gain of 16p (59% of samples) followed by gain of 20q (44% of samples), with the minimal overlapping regions at 16p13.1-p13.2 and 20q13.2, respectively. Other over-represented loci with > 30% frequency were observed at 5p (34% of samples), 7p (41% of samples), 8q (31% of samples), 17q (34% of samples), and 19q (34% of samples); and high-level DNA amplifications were detected at 1q, 7p, 12q, 19q, and 20q. DNA under-representation was observed less commonly and included 8p (28% of samples), 9p (22% of samples), 13q (28% of samples), and 18q (38% of samples).CONCLUSIONS
The current study identified targets of frequent genetic aberration in primary adenocarcinomas from nonsmokers. Compared with reported CGH findings in the literature, the current findings suggest that DNA gain at 16p is the distinct aberration involved in these tumors. Other frequently altered loci involve commonly reported oncogenic and tumor suppressor loci, suggesting an overlap with the genetic pathways of tobacco-induced lung carcinogenesis. Cancer 2003;97:1263–70. © 2003 American Cancer Society.DOI 10.1002/cncr.11183
Cancer 02/2003; 97(5):1263 - 1270. · 4.77 Impact Factor
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ABSTRACT: Pulmonary cryptococcosis is a very rare form of pneumonia, which is seldom seen among immunocompetent patients. We report the case of a 36-year-old man who presented with indolent pneumonia that was subsequently diagnosed to be pulmonary cryptococcosis without other systemic involvement. Contrary to formal belief, there was evidence of residual lung fibrosis 12 months after initial presentation. The features of pulmonary cryptococcosis reported in the Asian Pacific region are also reviewed.
Respirology 02/2002; 6(4):351 - 355. · 2.42 Impact Factor
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Matthew K. Wong, Maria P. Wong,
David C. Lam,
Alan Sihoe,
L.C. Cheng,
B. Lam,
Mary S. Ip,
T. Nakajima,
K. Yasufuku,
W.K. Lam,
James C. Ho
[show abstract]
[hide abstract]
ABSTRACT: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has recently been shown to be accurate in diagnosis and staging of mediastinal lymph node metastases. We report a case of squamous cell carcinoma diagnosed by endobronchial biopsy with concomitant contralateral hilar lymph node metastasis from small cell carcinoma being confirmed by EBUS-TBNA. The diagnosis of synchronous primary lung cancers in this case, which altered the treatment strategy, would not be made if pathological staging of intrathoracic lymph node was not pursued. The unique role of EBUS-TBNA in diagnosis of hilar lymphadenopathy was underscored. The potential pitfall of missing synchronous lung tumour if the diagnosis is based either on sampling from intrathoracic lymph node or from endobronchial lesion alone is discussed.
Lung Cancer.
