• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3255-3261
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• 2013

Background: The efficacy of erlotinib is controversial in patients with unknown EGFR mutational status. The aim of this study was to identify the clinicopathological factors that are predictive of erlotinob treatment outcomes for NSCLC patients with unknown EGFR mutational status. Materials and Methods: A retrospective analysis of 109 patients with advanced NSCLC who had previously failed at least one line of chemotherapy and received subsequent treatment with erlotinib (150 mg/day orally) was performed. A Cox proportional hazard model for univariate and multivariate analyses was used to identify the baseline clinical parameters correlating with treatment outcome, expressed in terms of hazard ratios (HRs) and 95% confidence intervals. Results: The median treatment duration was 15 weeks (range, 4-184). The disease control rate was 55%, including disease stability for ${\geq}3$ months for 40% of the patients. Median progression-free survival and median overall survival (OS) were 4.2 and 8.5 months, respectively. The Cox model indicated that an Eastern Cooperative Oncology Group performance status (ECOG PS) ${\geq}2$ (HR 3.82; p<0.001), presence of intra-abdominal metastasis (HR 3.42; p=0.002), 2 or more prior chemotherapy regimens (HR 2.29; p=0.021), and weight loss >5% (HR 2.05; p=0.034) were independent adverse prognostic factors for OS in NSCLC patients treated with erlotinib. Conclusions: This study suggests that NSCLC patients should be enrolled in erlotinib treatment after a first round of unsuccessful chemotherapy to improve treatment success, during which they should be monitored for intra-abdominal metastasis and weight loss.

• Journal of Chest Surgery
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• v.32 no.6
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• pp.536-542
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• 1999

Background: The purpose of this study is to improve the quality of the diagnostic procedures in the preoperative evaluation so as to reduce the unnecessary thoracotomy and to ensure resectability in non-small cell lung cancer. Material and Method: Of 616 patients who underwent thoracotomy for primary lung cancer from January 1990 to December 1996, 59 patients(9.6%) turned out to have inoperable lesions after the thoracotomy. We reprospectively reviewed the bronchoscopic findings, methods of tissue diagnosis, CT scans, pulmonary function test and lung perfusion scan, reasons for nonresectability, and adjuvant therapy, and then followed up on the survival rate after exploratory thoracotomy. Result: The cell types were squamous cell carcinoma in 38, adenocarcinoma in 15, large cell carcinoma in 3 and others in 3. Primary loci were RUL in 20, RML in 6, RLL in 8, LUL in 13, LLL in 4 and others in 8. The reasons for non-resectability were various; direct tumor invaison to mediastinal structures(n=41), seeding on pleural cavity(n=8), poor pulmonary function(n=2), invasions to extranodal mediastinal lymph node(n=2), technical non- resectability due to extensive chest wall invasion (n=3), small cell carcinoma (n=1), malignant lymphoma(n=1), and multiple rib metastases(n=1). In the follow-up of 58 patients, 1-year survival rate was 55.2% and 2-year survival rate was 17.2% and the mean survival time was 14 months. When compared according to cell types or postoperative adjuvant therapeutic modalities, no significant difference in the survival rates were found. The squamous cell carcinoma was frequently accompanied by local extension to contiguous structures and was the main cause of non-resectability. In adenocarcinoma, pleural seeding with malignant effusion was frequently encountered, and was the major reason for non-resectability. Conclusion: These data revealed that if appropriate preoperative diagnostic tools had been available, many unnecessary thoracotomies could have been avoided. Both the use of thoracoscopy in selected cases of adenocarcinoma and the more aggressive surgical approach to the locally advanced tumor could reduce the incidence of unnecessary thoracotomies for non-small cell lung cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6963-6966
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• 2015

Background: During the past few years, Hesa-A, a herbal-marine mixture, has been used to treat cancer as an alternative medicine in Iran. Based on a series of studies, it is speculated that Hesa-A possesses special cytotoxic effects on invasive tumors. To test this hypothesis, we investigated the selective anticancer effects of Hesa-A on several cancer cell lines with different metastatic potential. Materials and Methods: Hesa-A was prepared in normal saline as a stock solution of 10 mg/ml and further diluted to final concentrations of $100{\mu}/ml$, $200{\mu}g/ml$, $300{\mu}g/ml$ and $400{\mu}g/ml$. MTT-based cytotoxicity assays were performed with A549 (lung non small cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: All treated cancer cells showed significant (P<0.01) or very significant (P<0.0001) differences in comparison to negative control at almost all of the tested doses ($100-400{\mu}g/ml$). At the lower dose ($100{\mu}g/ml$), Hesa-A reduced cell viability to 66%, 45.3%, 35.5%, 33.2% in SKOV3, A549, PC-3 and MCF-7 cells, respectively. Moreover, at the highest dose ($400{\mu}g/ml$), Hesa-A resulted in 88.5%, 86.6%, 84.9% and 79.3% growth inhibition in A549, MCF-7, PC-3 and SKOV3 cells, respectively. Conclusions: Hesa-A exert potent cytotoxic effects on different human cancer cells, especially those with a high metastatic potential.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5101-5106
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• 2016

Purpose: We aimed to establish an inflammatory prognostic index (IPI) in early and advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze its predictive value for NSCLC survival. Materials and Methods: A retrospective review of 685 patients with early and advanced NSCLC diagnosed between 2009 and 2014 was conducted with collection of clinical, and laboratory data. The IPI was calculated as C-reactive protein ${\times}$ NLR (neutrophil/ lymphocyte ratio)/serum albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. Results: The optimal cut-off value of IPI for overall survival (OS) stratification was determined to be 15. Totals of 334 (48.8%) and 351 (51.2%) patients were assigned to high and low IPI groups, respectively. Compared with low IPI, high IPI was associated with older age, greater tumor size, high lymph node involvement, distant metastases, advanced stage and poor performance status. Median OS was worse in the high IPI group (low vs high, 8.0 vs 34.0 months; HR, 3.5; p<0.001). Progression free survival values of the patients who had high vs low IPI were determined 6 months (95% CI:5.3-6.6) and 14 months (95% CI:12.1-15.8), respectively (HR; 2.4, P<0.001). On multivariate analysis, stage, performance status, lactate dehydrogenase and IPI were independent prognostic factors for OS. Subgroup analysis showed IPI was generally a significant prognostic factor in all clinical variables. Conclusion: The described IPI may be an inexpensive, easily accessible and independent prognostic index for NSCLC patients, useful for clinical practice.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1119-1122
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• 2016

Background: Punica granatum (PG) has been demonstrated to possess antitumor effects on various types of cancer cells. In this study, we determined antiproliferative properties of a seed extract of PG (PSE) from Iran in different human cancer cells. Materials and Methods: A methanolic extract of pomegranate seeds was prepared. Total phenolic content (TPC) and total flavonoid content (TFC) were assessed by colorimetric assays. Antioxidant activity was determined with reference to DPPH radical scavenging activity. The cytotoxicity of different doses of PSE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) was evaluated by MTT assays with A549 (lung non small cell carcinoma), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all studied cancer cells, PSE reduced the cell viability to values below 23%, even at the lowest doses. In all cases, IC50 was determined at doses below $5{\mu}g/ml$. In this regard, SKOV3 ovarian cancer cells were the most responsive to antiproliferative effects of PSE with a maximum mean growth inhibition of 86.8% vs. 82.8%, 81.4% and 80.0% in MCF-7, PC-3 and A549 cells, respectively. Conclusions: Low doses of PSE exert potent antiproliferative effects on different human cancer cells SKOV3 ovarian cancer cells as most and A549 cells ar least responsive regarding cytotoxic effects. However, the mechanisms of action need to be addressed.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1457-1461
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• 2012

Purpose: Non small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting EGFR mutations have been developed, most advanced cases are still incurable. New targets for anticancer drugs are demanded. The kringle 1 domain of hepatocellular growth factor alpha chain (HGFK1) is a potent anti-angiogenesis factor. It has also emerged as a potential anticancer factor in hepatocellular carcinoma (HCC). The expression of HGFK1 protein in patients with NSCLC has not been reported to date. Method: Here, we assessed HGFK1 expression by Western blotting in 103 cases with advanced NSCLC to investigate the impact of HGFK1 on survival. Results: Results revealed 33 (30.1%) patients were classified as high expressors, this being significantly associated with less remote metastasis (P = 0.002) but not with lymph node metastasis (P = 0.062). There was also a significant association between HGFK1 expression and tumor size (P = 0.025) as well as clinical stage (P = 0.012). Kaplan-Meier survival analysis showed that both overall survival (OS) and progression free survival (PFS) of patients with HGFK1 expression were longer than those of patients without HGFK1 expression (P = 0.004 and P = 0.001 respectively). HGFK1 reversed gefitinib inhibition in the resistent NSCLC cell line A431/GR but did not inhibit the proliferation of NSCLC cells A431 and A431/GR directly. Reversion of gefitinib inhibition in A431/GR cells by HGFK1 was related to decreased phosphorylation of ERK and STAT5. Conclusions: HGFK1 may be a useful prognostic factor of advanced NSCLC patients and a potential drug for gefitinib resistant patients.

• Tuberculosis and Respiratory Diseases
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• v.66 no.4
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• pp.324-328
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• 2009

The syndrome of inappropriate secretion of the antidiuretic hormone (SIADH) is a well recognized paraneoplastic phenomenon related to impaired water excretion, and can result in dilutional hyponatremia as well as central nervous system symptoms. It is characterized by a decrease in plasma osmolarity with inappropriately concentrated urine. The causes of SIADH are associated with pulmonary and endocrine disorders, central nervous system diseases, and malignancies, including lung cancer. The other causes of SIADH include some drugs, particularly chemotherapy agents. Anticancer drugs, such as cisplatin, vincristine, and cyclophosphamide are well known causes of SIADH but the mechanisms are unclear. Recently, we encountered a patient with advanced non-small cell lung cancer who suffered from general weakness and altered mentality after an intravenous carboplatin and gemcitabine combination.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.309-316
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• 2002

Background: To evaluate the efficacy and toxicity of combination chemotherapy using ifosfamide, cisplatin, and etoposide in patients with advanced non-small cell lung cancer(NSCLC). Materials and methods: Thirty-three patients with inoperable NSCLC(stage IIIb+IV) who had measurable diseases, and had not been treated with chemotherapeutic drugs, were enrolled in this study(from March 1995 to December 1996). The patients received ifosfamide($1500mg/m^2/day$, a full drop with Mesna on days 1-5), Cisplatin ($80mg/m^2/day$ infusion with a hydration on day 2), and Etoposide ($100mg/m^2/day$ infusion for 2 hours on days 1-3). The treatment was repeated every 4 weeks. Results: Ten patients showed a partial responses (30.3%). The overall survival time of the responders was longer than that of the non-responders (median 55 vs 22 weeks, p=0.01). The toxicities of this treatment were tolerable. Grade 3 or 4 leukopenia was observed in 21%. There was 1 death related to febrile neutropenia. The non-hematologic toxicity was mild. The relative dose intensity given to the patients was 0.86 ifosfamide, 0.87 cisplatin, and 0.89 etoposide, showing an average dose intensity of 0.87. Conclusions: A combination regimen of ifosfamide, cisplatin, and etoposide is effective and tolerable for treating advanced non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.68 no.5
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• pp.286-289
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• 2010

A 55-year old woman with advanced stage non-small cell lung cancer was admitted to hospital for the management of severe chest pain, which measured 7 out of 10 on a numerical rating scale (NRS). Despite palliative radiation and the application of multiple epidural blocks, she continued to experience severe cancer pain. We gradually increased the dose of transdermal fentanyl patches from $500{\mu}g/hr$ to $3,650{\mu}g/hr$, for 3 months without any significant side effects. Concomitantly, adjuvant therapy with antidepressants and anticonvulsants were added, decreasing the patient's pain to NRS 3~4 down from 7. After being transferred to a hospice clinic, her chest pain was well-controlled below NRS 4 by means of strong opioid medications, including the highest dose of transdermal fentanyl $4,050{\mu}g/hr$ for more than 16 months.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6779-6782
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• 2015

Background: Chemoradiotherapy is an important treatment modality for lung cancers. The aim of this study was to investigate alterations in, as well as the interrelationship between, lung function and quality of life of patients receiving chemoradiotherapy due to locally advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) limited to the thorax. Materials and Methods: The study included patients receiving definitive chemoradiotherapy for lung carcinoma. The respiratory function of the patients was assessed by measuring forced expiratory volume in 1 s per unit (FEV1) and forced expiratory volume in 1s per unit of vital capacity (FEV1/VC) before, in the middle of and after treatment. During the study, EORTC QLQ C30 and LC13 questionnaires developed by the Committee of the European Organization for Research and Treatment of Cancer (EORTC) were employed to evaluate the quality of life on the same day as respiratory function tests (RFT). Findings: The study included 23 patients in total: 19 (82.6%) diagnosed with NSCLC and 4 (17.4%) with SCLC. The average percentage FEV1 was $55.6{\pm}21.8%$ in the pre-treatment period, $56.2{\pm}19.2%$ in the middle of treatment and $60.4{\pm}22%$ at the end of treatment. The improvement in functional scores, symptom scores and general health scores during treatment was not statistically significant (P= 0.568, P= 0.734, P= 0.680, P=0.757 respectively). Conclusions: Although this study showed an improvement in respiratory function and quality of life of patients during treatment with thoracic chemoradiotherapy, no statistically significant results were obtained. While evaluating the effectiveness of treatments for lung carcinoma, the effects of treatment on respiratory function and quality of life should be considered.