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Primary lung enteric adenocarcinoma is a rare type of invasive lung carcinoma. Its morphology and immunohistochemistry are those of colorectal carcinoma, but there is no associated primary colorectal carcinoma. The present study describes the case of a 53-year-old female who presented with an irritating cough and a mass around the right sternoclavicular joint. Comprehensive evaluation revealed involvement of the mediastinum, lungs, right sternoclavicular joint and right kidney. Biopsies from the mediastinal and right sternoclavicular joint tumors showed features of adenocarcinoma. Immunohistochemistry was positive for cytokeratin (CK)20 and caudal type homeobox transcription factor 2, and negative for CK7, thyroid transcription factor-1 and napsin A. Genotypic analysis identified the expression of wild-type epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene homolog, serine/threonine-protein kinase B-Raf and UDP-glucuronosyltransferase 1-1. There was no expression of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase and a moderate expression of excision repair cross-complementation group 1, ribonucleoside-diphosphate reductase large subunit and tubulin β-3 chain. A strong expression of thymidylate synthase and 677TC genotype expression of methylenetetrahydrofolate reductase was observed. Gastroscopy, enteroscopy, colorectal colonoscopy and positron emission tomography-computed tomography failed to find evidence of a gastrointestinal malignancy and primary lung enteric adenocarcinoma was diagnosed. The presence of multiple metastases did not permit curative surgery. The patient was treated with 3 monthly cycles of the XELOX chemotherapy regimen; the response was poor with progression of supraclavicular lesions. Treatment was switched to the TP regimen for 4 monthly cycles, which resulted in a significant reduction in the size of the lung lesions; however, the supraclavicular lesion responded poorly to the treatment. The patient then received 2 cycles of the FOLFIRI regimen; however, the lung and right supraclavicular lesions progressed, causing increased right upper limb pain. The pain was alleviated by palliative surgery. Following surgery, the DP regimen was employed. Follow-up of the patient remains ongoing. The present findings suggest that the early diagnosis and treatment of primary lung enteric adenocarcinoma is likely to improve patient outcome.

Objective: To detect K-ras gene mutations in plasma free DNA by peptide nucleic acid clamp PCR assay (PNA-PCR) and nested primer PCR, and to analyze the correlation between K-ras mutations and prognosis in patients with metastatic colorectal cancer (mCRC)., Methods: Peripheral blood was collected and free DNA was extracted from plasma in 106 patients with mCRC. Nested primer PCR and PNA-PCR were used to detect K-ras gene mutation in the plasma free DNA. The patients were divided into three groups by K-ras status: wild-type group (wild-type determined by both methods), low mutation group (mutation by PNA-PCR method, wild-type by nested primer PCR method) and high mutation group (mutation by two methods). The correlation between K-ras mutations and prognosis was analyzed., Results: The mutation rate of K-ras in tumor tissues of the 106 patients was 40.6%. The Mutation rate of K-ras in plasma free DNA detected by PNA-PCR was 31.1%, significantly higher than that of 15.1% detected by nested primer PCR (P = 0.006). The consistent rate of the K-ras status in plasma free DNA detected by PNA-PCR and that in tumor tissue detected by traditional method was up to 83.0%. The median overall survival (OS) of patients of the wild type, low mutation and high mutation groups was 23.5 months, 17.3 months and 13.9 months, respectively (P = 0.002). The median progression-free survival (PFS) of the K-ras wild-type, low mutation and high mutation groups with first-line chemotherapy was 6.8 months, 6.1 months and 3.2 months, respectively (P = 0.002), and the median OS of them were 23.0 months, 15.5 months and 13.9 months, respectively (P = 0.036). The overall response rate (ORR) was improved in the K-ras wide-type patients who received cetuximab combined with chemotherapy as first-line therapy (75.0% vs. 23.4%, P = 0.058). Cetuximab combined with in second-line therapy chemotherapy led to a significant improvement in disease control rate (DCR) ( 100% vs. 35.7%, P < 0.001) as compared with those of chemotherapy alone. COX regression model showed that K-ras status detected by PNA-PCR, ECOG PS, number of surgery and initially metastatic site were independent factors for prognosis., Conclusions: PNA-PCR for the detection of K-ras mutation in plasma free DNA can be used to substitute the traditional method for detection of K-ras mutation in tumor tissues. The abundance of K-ras mutation in plasma free DNA is an independent prognostic factor for patients with metastatic colorectal cancer.

Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bearing UGT1A1 28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of irinotecan are advised that patients with UGT1A1 28 (TA 7/7) should start with a reduced dose of irinotecan, although a particular dose is not specified. Research in Asian countries has shown a lower incidence of UGT1A1 28 (TA 7/7), while UGT1A1 6 (A/A) is more often found and is associated with severe irinotecan-related neutropenia. We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1 28 polymorphism (TA 6/7) as well as the UGT1A1 6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinotecan dose reductions according to pharmacokinetic data regarding exposure to the active metabolite, SN-38. Simultaneous heterozygous UGT1A1 28 and UGT1A1 6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinotecan. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1 28 and UGT1A1 6 polymorphisms.

Objective: To evaluate the correlation of clinical effect and prognosis between patients with metastatic colorectal cancer (mCRC) and different K-ras status., Methods: The clinical characteristics, chemotherapeutic regimens and survival of 153 mCRC patients with different K-ras status were analyzed retrospectively., Results: The median overall survival (OS) in patients without K-ras mutation were 31.7 months, significantly longer than 21.3 months in the patients with K-ras mutation (P = 0.037). The median progression-free survival (PFS) and OS in patients who received chemotherapy followed by anti-EGFR antibody treatment were 11.5 and 39.3 months, respectively, significantly longer as compared with the PFS and OS in those received chemotherapy in combination with anti-EGFR antibody concomitantly (5.7, P = 0.02, and 28.7 months, P = 0.034, respectively)., Conclusions: K-ras status is a prognostic biomarker for mCRC patients treated with anti-EGFR antibody. The combination settings of anti-EGFR in combination with chemotherapy may improve survival of mCRC patients with wild-type K-ras status.

Objective: To evaluate the current clinical treatment status of gastric cancer in China., Methods: A retrospective analysis of clinicopathological characteristics of 636 patients with gastric cancer was conducted. Tumor response was evaluated using RECIST version 1.1 criteria., Results: Six hundred and thirty-six patients were included in this retrospective cohort: 479 men and 157 women. The median age was 57 years (14 to 86). The tumor site was: proximal (41.4%), distal (46.4%) or unknown (12.2%). The histology was: adenocarcinoma (85.8%), signet ring cell carcinoma (6.9%), or other and unknown (7.2%). The differentiation of the adenocarcinomas was: well differentiated (31.0%), moderately differentiated (13.4%), poorly differentiated (37.0%), or unknown (18.7%). The pTNM stage was: 0 (0.3%), I (3.6%), II (10.1%), III (36.8%), IV (45.6%), or unknown (3.6%). In 284 patients who underwent radical resection, the ratio of examined ten and/or more lymph nodes was higher in hospitals at or above provincial level than in hospitals at regional level (57.9% vs. 39.6%, P = 0.009). The disease-free survival was longer (21.7 m vs. 14.6 m, P = 0.005), and the overall survival was longer too (52.9 m vs. 33.8 m, P = 0.040). In 205 patients who received adjuvant chemotherapy, the ratio of administered six and/or more cycles chemotherapy was 42.1% vs. 35.2% (P = 0.318), and the disease-free survival was 22.7 m vs. 16.3 m (P = 0.005) between hospitals at or above provincial level and hospitals at regional level. In 387 patients with metastatic or unresectable gastric cancer who received palliative chemotherapy, the overall survival was 11.1 m (95%CI 9.9 - 12.3 m). Among them, 198 patients received second and/or more line chemotherapy, and the overall survival was longer (12.5 m vs. 7.7 m, P < 0.001). Except a longer progression-free survival (10.2 m, P < 0.05) and a longer overall survival (16.9 m, P < 0.05) were corresponded with the regimen containing trastuzumab, no other significant difference was observed among regimens in first line chemotherapy., Conclusion: Chinese doctors working in different level hospitals have a different understanding of the treatment standard of gastric cancer, which resulted in different outcomes.

Objective: To assess the HER-2 status in Chinese advanced gastric cancer patients and explore its correlation with clinical features, treatment response and prognosis., Methods: A total of 107 patients with advanced gastric cancer treated in our hospital from December 2005 to November 2008 were included in this retrospective analysis. HER-2 status was determined by immunohistochemisty (IHC) and/or fluorescence in situ hybridization (FISH). The correlations of HER-2 status with tumor location, pathology, treatment response and prognosis were analyzed and the efficacy of different chemottherapy regimens was compared., Results: The overall positive rate of HER-2 expression was 14.7% (15/102). The HER-2 status was detected by both methods in 102 patients, and the concordance of the two methods was 66.5%. The tumor site distribution was gastroesophageal junction (GEJ) 28.0%, proximal stomach 19.4%, gastric corpus 16.1%, antrum 26.9% and whole stomach 9.7%, respectively. There was no significant difference of HER-2 status among different tumor sites (P = 0.726), and no significant correlation between HER-2 expression and differentiation (P = 0.110). Among the evaluable 51 patients treated by first-line chemotherapy, the total objective effective rate was 23.5%. The median time-to-progression was 7.47 months, and median overall survival time was 11.07 months. The effective rate was 43.8% in patients who received XP regimen chemotherapy (cisplatin + capecitabine), significantly higher than the 14.3% in patients treated with other regimens (P = 0.033). Their overall survival was 14.17 months and 9.53 months, respectively (P = 0.059). The TTP was 6.63 months in HER-2 positive patients and 7.47 months in HER-2 negative patients, with a non-significant difference (P = 0.510). However, there was a improving tendency in the efficacy and OS, showing a effective rate of 45.5% and 17.5% (P = 0.102) and OS of 14.17 months and 10.63 months, respectively (P = 0.205)., Conclusions: HER-2-positivity rate in Chinese patients with advanced gastric cancer is similar to those reported in the literature. Along with the increasing use of targeted therapy and targeted agents, the efficacy and survival of gastric cancer patients is improving. HER-2-positive patients may benefit from it.

Objective: To assess the efficacy and safety of bevacizumab plus irinotecan-based regimen for the first line treatment in metastatic colorectal cancer (mCRC) patients, and to investigate the correlation between serum tumor markers including CEA and CA19-9 and response as well as prognosis., Methods: From May 2007 to July 2008, 67 previously untreated mCRC patients received treatment of IFL (n = 25), IFL plus Bevacizumab (n = 20) or FOLFIRI (n = 22). The treatment continued until disease progression or unacceptable toxicity. The data were retrospectively analyzed., Results: All patients were evaluable for response, survival and toxicity analysis. The objective response rate of IFL, IFL plus Bevacizumab or FOLFIRI regimen groups was 16.0% (4/25), 35.0% (7/20) and 18.2% (4/22), respectively (χ(2) = 6.026, P = 0.049). The median progression-free survival (PFS) of IFL plus bevacizumab group was 7.5 months, significantly improved as compared with 3.7 months in the IFL group and 4 months in FOLFIRI group (χ(2) = 11.97, P = 0.003). Of all 67 cases, the one-year survival rate was 47.0%, two-year survival rate was 27.0%, and the median overall survival (OS) was 13.0 months, with no significant difference among the three treatment groups (χ(2) = 3.42, P = 0.18). The serum CEA and CA19-9 levels were decreased after treatment, but with no significant difference among the three groups (P > 0.05). The common toxicity profiles of IFL and FOLFIRI regimens were diarrhea and neutropenia, while the toxicity related to bevacizumab was consistent with that documented in previous literature, such as hypertension, hemorrhage, cardiac toxicity and delayed wound healing., Conclusion: The addition of bevacizumab to irinotecan-based regimen significantly improves the response rate and PFS in first-line treatment for patients with mCRC and its toxicity is well tolerated.

Aim: To evaluate the therapeutic efficiency of replicative adenovirus CNHK300 targeted in telomerase-positive hepatocellular carcinoma., Methods: CNHK300, ONYX-015 (55 kDa protein deleted adenovirus) and wtAd5 (wild type adenovirus 5) were compared, and virus proliferation assay, cell viability assay, Western blot and fluorescence microscopy were used to evaluate the proliferation and cytolysis selectivity of CNHK300., Results: The replicative multiples in Hep3B and HepG II after 48 h of CNHK300 proliferation were 40625 and 65326 fold, respectively, similar to that of wtAd5. However, CNHK300 exhibited attenuated replicative ability in normal fibroblast cell line BJ. CNHK300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI., Conclusion: CNHK300 is a cancer-selective replication-competent adenovirus which can cause oncolysis of liver cancer cells as well as wtAd5 (wild type adenovirus 5), but had severely attenuated replicative and cytolytic ability in normal cells. This novel strategy of cancer treatment offers a promising treatment platform.

Background & Objective: ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has clinical antitumor activity, but its efficacy is low. This study was to assess the effects of ZD1839 in combination with oxaliplatin on lung adenocarcinoma cell line A549, and to provide pre-clinical evidence for optimizing the schedule of oxaliplatin combined with ZD1839., Methods: Chou and Talalay method was used to analyze the combination effects of sequencing ZD1839 and oxaliplatin on A549 cells. Cell cycle distribution and cell apoptosis were analyzed by flow cytometry. The effects of oxaliplatin combined with ZD1839 on the proliferation of A549 cells in nude mice were also evaluated., Results: Sequential oxaliplatin followed by ZD1839 produced synergistic effect, with a combination index (CI) of 0.51+/-0.01. In contrast, ZD1839 followed by oxaliplatin exhibited antagonist effect, with a CI of 1.56+/-0.03. Compared with other sequences, oxaliplatin followed by ZD1839 induced more cells being arrested in G(2/M) phase (37.9%, P<0.05); the apoptosis rate was 22.3%. The inhibition rate of tumor growth in nude mice was 58.9% when treated with oxaliplatin followed by ZD1839, 52.4% when treated with oxaliplatin and ZD1839 for 24 h and followed by ZD1839 for additional 48 h, and 30.6% when treated with ZD1839 followed by oxaliplatin., Conclusion: Sequential oxaliplatin followed by ZD1839 has the maximal inhibitory effect on the proliferation of A549 cells.