• Journal of Pharmaceutical Investigation
• /
• v.36 no.4
• /
• pp.231-237
• /
• 2006

Hypoxia in solid tumors is known to contribute to intrinsic chemoresistance. Histocultures are in vitro 3 dimensional cultures of tumor tissues and maintain the characteristic microenvironment of human solid tumors in vivo including hypoxia and multicellular structure. In this study, we evaluated the pharmacodynamics of tirapazamine(TPZ), a hypoxia-selective cytotoxin, in human non small cell lung cancer(NSCLC) cells grown as monolayers and histocultures. Antiproliferative activity of TPZ was determined after various conditions of drug exposure, and cell cycle arrest and apoptosis were also measured using flow cytometry. In monolayers, hypoxia selectivity measured by hypoxic/normoxic cytotoxicity ratio was increased with longer exposure. Lower cytotoxicity of TPZ was observed in histocultures compared to monolayers, however, a similar level of cytotoxicity was obtained with longer exposure of 96 hr. TPZ induced $G_2/M$ arrest and apoptosis in both culture conditions, which were greatly enhanced under hypoxic condition. Our data clearly showed the different pharmacodynamics of TPZ in monolayers and histocultures. Antiproliferative activity of TPZ against human solid tumors can be improved with longer drug exposure by exploiting drug delivery systems or by combining angiogenesis inhibitors to maintain drug concentration in tumor tissues.

• Food Science and Biotechnology
• /
• v.15 no.3
• /
• pp.458-461
• /
• 2006

To determine whether the toxicity of Bacillus cereus would be seen in human cell lines and mice, we screened B. cereus B-38B, B. cereus B-50B, and B. cereus KCCM40935 for genes that coded for 5 enterotoxins using the polymerase chain reaction and cultivated them for 17 hr, by whose time they had grown to $10^7-10^8$ colony-forming units (CFU) per milliliter. Cell-free supernatant was added to make up 1% of the total reaction solution. Human cells from normal lung, lung carcinoma, embryonic kidney, and cervical adenocarcinoma cell lines were grown in culture. The cytotoxicity induced by adding the reaction solution was indicated by cell death rates of 0 to 70%, depending on the bacterial strain involved and the cell line. A lethality of 20% was observed when B. cereus cultures containing $10^7-10^8$ viable cells were administrated orally to mice. Therefore, the culture of B. cereus containing $10^7-10^8$ viable cells seems to have high cytotoxicity on human cell lines and lethality on mice.

• Journal of Chest Surgery
• /
• v.31 no.12
• /
• pp.1200-1205
• /
• 1998

Background: Lung cancer formation is a multistage process involving activation of protooncogene and inactivation of tumor suppressor genes. We evaluate the significance of cyclin D1, p53, bcl-2 gene mutations in patients with curatively resected stage IIIA non-small cell lung cancer(NSCLC). Material and Method: One hundred consecutive cases of stage IIIA lung cancers from patients operated on curatvely between 1990 and 1995 for which adequate paraffin blocks and clinical history were available. Immunohistochemical studies were performed on the representative tissue sections from each case by the labelled streptovidin- biotin method. Sections for cyclin D1, p53, Bcl-2 immunostaining were pretreated in a microwave oven for 10 to 20 minutes in citrate buffer before immunostaining. The overnight incubation with NCL-cyclin D1-GM for cyclin D1, with clone DO-7 for p53, with clone 124 for bcl-2 was done. Mean follow-up was 24.1 months (range 2-84 months) after operation. Result: One hundred cases of lung cancers were composed of 56 cases of squamous cell carcinoma, 37 cases of adenocarcinoma, 5 cases of adenosquamous cell carcinoma, and 2 cases of large cell carcinoma. The 5-year survival was 32.1%. The positive expression rate of cyclin D1 was 35%, p53 was 56%, and bcl-2 was 17%. But there were no correlation between cyclin D1, p53, Bcl-2 protein expression and survival. Conclusion: These observation indicate that cyclin D1, p53, bcl-2 protein overexpression might be implicated in the oncogenesis of non-small cell lung carcinomas but they have no usefulness as a prognostic marker.

• Tuberculosis and Respiratory Diseases
• /
• v.85 no.2
• /
• pp.155-164
• /
• 2022

Background: The remarkable efficacy of osimertinib in non-small cell lung cancer (NSCLC) with acquired T790M mutation has been widely documented in clinical trials and real-world practice. However, some patients show primary resistance to this drug. Even patients who initially show a favorable response have inconsistent clinical outcomes later. Therefore, the aim of this study was to identify additional clinical predictive factors for osimertinib efficacy. Methods: A prospective cohort of patients with acquired T790M positive stage IV lung adenocarcinoma treated with osimertinib salvage therapy in Hallym University Medical Center were analyzed. Results: Sixty-one eligible patients were analyzed, including 38 (62%) women and 39 (64%) who never smoked. Their mean age was 63.3 years. The median follow-up after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) was 36.0 months (interquartile range, 24.7-50.2 months). The majority (n=45, 74%) of patients were deceased. Based on univariate analysis, low baseline neutrophil-to-lymphocyte ratios (NLR), age ≥50 years, never-smoking history, stage IVA at osimertinib initiation, and prolonged response to previous TKIs (≥10 months) were associated with a significantly longer progression-free survival (PFS). Multivariate analysis showed that never-smoking status (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.30-0.98; p=0.041) and a baseline NLR less than or equal to 3.5 (HR, 0.23; 95% CI, 0.12-0.45; p<0.001) were independently associated with a prolonged PFS with osimertinib. Conclusion: Smoking history and high NLR were independent negative predictors of osimertinib PFS in patients with advanced NSCLC developing EGFR T790M resistance after the initial EGFR-TKI treatment.

• Journal of Korean Traditional Oncology
• /
• v.12 no.1
• /
• pp.67-73
• /
• 2007

Breast cancer is common in West and Incidence of breast cancer has increased in Korea. According as conventional western medical treatment, breast cancer patient received MRM(modified radical mastectomy) and anti cancer chemotherapy. In this case report, We introduce a case of breast cancer patient who showed lung metastasis(metastatec adenocarcinoma) after MRM(modified radical mastectomy) 4 years before the diagnosis of relapse. After lung metastasis of breast cancer, the patient received 4th chemotherapy and refused to get more conventional western medical treatment including chemotherapy. After 24 month of traditional oriental medical treatment using allegen removed Rhus Verniciflua Stokes(ARV), however, the size of cancer mass decreased and the patient showed improved condition. Further case study will be needed in order to determine the effect of ARV on breast cancer patient.

• Radiation Oncology Journal
• /
• v.4 no.1
• /
• pp.55-62
• /
• 1986

From Nov. 1983 through Jan. 1986, 43 patients with nonsmall cell lung cancer were treated by radiation therapy at Inje Medical College Paik Hospital. 38 patients were available for the analysis of this study. 33 patients received definite irradiation with curative intent, while 5 patients received postoperative irradiation. Chemotherapy was added in 12 patients before, during and after radio-therapy. 28 patients were squamous cell carcinoma and 10 patients were adenocarcinoma. There were 29 men and 9 women (median age, 50 years; range 34 to 74 years). Stage 1 was 1 patient, Stage 11,7 patient, and Stage 111,30 patients. Among 33 patients who received radiotherapy with curative intent, follow up radiological study revealed complete response in 12 patients $(36\%)$, partial response, in 9 patients $(27\%)$, and minimal response, in 5 patients $(15\%)$, while 7 patients $(21\%)$ were nonresponders. Median survival for all patients was 6.9 months; squamous cell carcinoma, 7.3 months, adenocarcinoma, 5.9 months. Responders survived median 7 months, while nonresponders survived median 1.9 months. Improved complete response rate and survival were shown in high radiation dose group. As prognostic factors, age, initial performance status, sex, histology and tumor location were evaluated.

• Journal of Chest Surgery
• /
• v.37 no.11
• /
• pp.937-941
• /
• 2004

Epithelioid hemangioendothelioma, originating from the vascular endothelium, is a very rare and low-grade malignancy. World-wide, about 50 cases of pulmonary epithelioid hemangioendothelioma have been reported. This is more common in female and is usually shown as multiple nodules in both lung fields. A 41-year-old male, who had suffered from right pleuritic chest pain for 3 months, was initially diagnosed as adenocarcinoma under bronchofiberscopic biopsy. At that time, the stage of tumor according to the TNM staging was llla. He received bronchoscopic biopsy again during follow-up period and it was diagnosed as hamartoma. After surgery, the final diagnosis was pulmonary epithelioid hemangioendothelioma.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.2
• /
• pp.273-280
• /
• 1999

This is a report of gastric metastases secondary from a primary small cell carcinoma of the lung in two men. Blood-borne metastatic involvement of the stomach by cancer is a rare entity. According to the reports in the literature the prevalence of metastasis to the stomach occurs in 0.4% and the most common cell type of the primary lung carcinoma is large cell type(3.7%) followed by adenocarcinoma(2.4%), small cell carcinoma(1.7%) and squamous cell carcinoma(0.7%). The most common tumors that spread to the stomach through the blood stream are malignant melanoma, breast carcinoma and lung carcinoma. Most of the gastrointestinal tract metastases had no specific symptoms because of its submucosal involvement. The prognosis was poor and the mean survival period from the onset of symptoms was 49 days. The first patient was a 56-year-old man who had primary lung carcinoma with brain metastasis. Gastroscopic findings showed two elevated mass lesions in the anterior wall of the mid body with central ulcer and the posterior wall of the fundus with intact surface mucosa. Pathologic examination of stomach tissue revealed small cell type tumor cells infiltrate in the stomach wall segmentally without destruction of the glands. The second patient was a 67-year-old man who had no other evidence of the distant metastasis. Gastroscopic findings showed a huge, oval shaped, ulcerofungating mass with deep penetrating central ulcer coated with dirty exudate in the anterior wall from mid to upper body of the stomach, and thickened elevated rugal folds in the posterior wall of the fundus. Pathologic examination of stomach tissues revealed the small cell type tumor cells showing small smudged nucleus infiltrate into the mucosa of the stomach and the architecture of mucosa intact. We report the two cases of metastatic gastric cancer from the primary small cell lung carcinoma with the literature review.

• Tuberculosis and Respiratory Diseases
• /
• v.65 no.2
• /
• pp.147-151
• /
• 2008

Non-resolving or slowly resolving pulmonary infiltrates in spite of administering adequate antimicrobial therapy are a clinical diagnostic challenge for physicians. The rate of radiographic resolution varies with the patients' age, the underlying comorbidities, the extent of radiographic involvement, the functional status and the causal pathogens. It is important to differentiate non-resolving or slowly resolving bacterial pneumonia from other uncommon infectious pneumonias or malignancies that require invasive diagnostic techniques to confirm the diagnosis. Bronchioloalveolar carcinoma can present with various clinical and radiographic features. Unfortunately, the radiographic similarity of consolidative BAC to pneumonia often leads to an incorrect diagnosis of pneumonia and possibly significant delays in obtaining appropriate diagnostic studies. We describe here a case of a mixed adenocarcinoma and bronchioloalveolar carcinoma that was initially diagnosed as pneumonia due to the consolidation pattern on the radiography and the patient's initial improvement with antibiotic treatment.

• Tuberculosis and Respiratory Diseases
• /
• v.57 no.5
• /
• pp.461-464
• /
• 2004

Signet ring cell carcinoma (SRCC) of the lung is a rare variant of pulmonary adenocarcinoma. Because the majority of SRCCs in the lung are metastatic tumors from stomach, colon, or breast. The differential diagnosis of primary SRCC from metastatic SRCC is important but may be problematic. Recently, immunohistochemical studies are known to be valuable in determining primary sites of SRCC. Herein, we present a case of primary signet ring cell carcinoma of the lung in a 67-year-old man. Even though radiographic findings of our case were more suggestive of metastatic orgin of SRCC in the lung, we could finally conclude that lung was the primary site of SRCC with the help of immunohistochemical studies (positive TTF-1 and CK7, and negative CK 20) and other diagnostic work up.