Biomedical subjects

Kun-Lin Tsai

Publications and source records attributed to Kun-Lin Tsai.

4 recordsLinked to original sources

PubMed2006

ErbB3-dependent motility and intravasation in breast cancer metastasis.

A better understanding of how epidermal growth factor receptor family members (ErbBs) contribute to metastasis is important for evaluating ErbB-directed therapies. Activation of ErbB3/ErbB2 heterodimers can affect both proliferation and motility. We find that increasing ErbB3-dependent signaling in orthotopic injection models of breast cancer can enhance intravasation and lung metastasis with no effect on primary tumor growth or microvessel density. Enhanced metastatic ability due to increased expression of ErbB2 or ErbB3 correlated with stronger chemotaxis and invasion responses to heregulin beta1. Suppression of ErbB3 expression reduced both intravasation and metastasis. A human breast cancer tumor tissue microarray showed a significant association between ErbB3 and ErbB2 expression and metastasis independent of tumor size. These results indicate that ErbB3-dependent signaling through ErbB3/ErbB2 heterodimers can contribute to metastasis through enhancing tumor cell invasion and intravasation in vivo and that ErbB-directed therapies may be useful for the inhibition of invasion independent of effects on tumor growth.

Animals↗

PubMed2006

Epidermal growth factor receptor overexpression results in increased tumor cell motility in vivo coordinately with enhanced intravasation and metastasis.

Although overexpression of the epidermal growth factor receptor (EGFR; ErbB1) has been correlated with poor prognosis in breast and other cancers, clinical trials of ErbB1 inhibitors have shown limited efficacy in inhibiting tumor proliferation. To evaluate other possible roles of ErbB1 in tumor malignancy besides proliferation, we have developed a series of tools for analysis of intravasation. Overexpression of ErbB1 in MTLn3 mammary adenocarcinoma cells results in increased intravasation and lung metastasis from tumors formed by injection of cells in the mammary fat pad. However, increased ErbB1 expression has no effect on primary tumor growth and lung seeding efficiency of cells injected i.v. Chemotactic responses to low concentrations of EGF in vitro and cell motility in vivo in the primary tumor measured using intravital imaging are significantly increased by ErbB1 overexpression. The increased cell motility is restricted to ErbB1-overexpressing cells in tumors containing mixtures of cells expressing different ErbB1 levels, arguing for a cell-autonomous effect of increased ErbB1 expression rather than alteration of the tumor microenvironment. In summary, we propose that ErbB1 overexpression makes more significant contributions to intravasation than growth in some tumors and present a novel model for studying ErbB1 contributions to tumor metastasis via chemotaxis and intravasation.

Adenocarcinoma↗

PubMed2004

Pulmonary atelectasis: a frequent alternative diagnosis in patients undergoing CT-PA for suspected pulmonary embolism.

The purpose of the study was to evaluate the prevalence of atelectasis as an alternative diagnosis in patients who underwent computed tomographic pulmonary angiography (CT-PA) for suspected pulmonary embolism (PE), and to contrast the pathophysiology of pulmonary atelectasis and PE, both of which are associated with dyspnea and hypoxemia. We retrospectively identified 144 consecutive emergency department patients (n=49) and inpatients (n=95) admitted between July 2001 and June 2002 who were evaluated with CT-PA for suspected PE. There were 98 women and 46 men with a mean age of 58 years (range 27-95 years). Each CT report was reviewed for PE, the words "atelectasis," "collapse," and/or "volume loss," findings known to predispose to atelectasis, and alternative diagnoses. CT scans of those with PE and those with atelectasis were reviewed. Each case was categorized into one of three groups, as follows: group 1, PE; group 2, atelectasis of three or more segments and no PE; group 3, neither PE nor atelectasis. PaO2 was documented, when available (n=115), with PaO2 >100 mmHg recorded as 100 mmHg. Reports for group 3 were reviewed for alternative diagnoses. Thirteen percent of the study population (19/144, group 1) had PE, and two of them had concomitant atelectasis; mean PaO2 was 69 mmHg (range 38-100 mmHg). Nineteen percent of the study population (27/144, group 2) had atelectasis of three or more segments without PE; mean PaO2 was 73 mmHg (range 45-100 mmHg). Sixty-eight percent of the study population (98/144, group 3) had neither PE nor atelectasis; mean PaO2 was 79 mmHg (range 36-100 mmHg). There was a significant difference in the PaO2 between groups 1 and 3 (Student's t-test), with group 2 intermediate. Seventy percent of group 2 (19/27) had at least one finding predisposing to atelectasis: central bronchial abnormality (n=6), moderate or larger pleural effusion (n=11), pleural mass, pneumothorax, elevated hemidiaphragm, and severe kyphosis (the last four all n=1 each), versus 16% (3/19) of group 1 ( P<0.05). Sixty-three percent of group 3 (62/98) had one or more alternative diagnoses on CT that explained the patient's symptoms as follows: pneumonia (28%, 27/98), other lung disease (18%, 18/98), congestive heart failure (13%, 13/98), and malignancy (13%, 13/98). Pulmonary atelectasis was common in patients undergoing CT-PA for suspected PE, equaling pneumonia as the most common alternative diagnosis. Most patients with atelectasis had predisposing findings on CT. Pulmonary atelectasis and PE cause similar symptoms by different mechanisms of ventilation-perfusion mismatch.

Adult↗

PubMed2002

Tuberculous meningitis in infancy.

The lack of specific symptoms and signs in patients with tuberculous meningitis makes early diagnosis difficult. To our knowledge, there has been no report in the literature focusing on tuberculous meningitis patients younger than 1 year of age. In this report, we reviewed the clinical features and laboratory findings of seven infants with tuberculous meningitis encountered during a 15-year period. All patients had fever, cough, and alternation of consciousness at presentation. Five patients had bulging anterior fontanel, and five had generalized tonic-clonic seizures. The purified protein derivative skin test was positive in six patients. Six patients had hyponatremia. All seven patients had abnormal cerebrospinal fluid findings, and six of them demonstrated cell counts less than 500 cells/mm(3) with lymphocytic predominance. Brain sonography examination revealed hydrocephalus in all seven patients. Therefore we conclude that antituberculosis therapy should be promptly initiated in any young infant with a clinical impression of meningitis in the context of cerebrospinal fluid white cell count of less than 500 cells/mm(3) and lymphocytic predominance, hyponatremia, and hydrocephalus.

Antitubercular Agents↗