Alpha-fetoprotein-producing hepatoid adenocarcinoma of the lung responsive to sorafenib after multiline treatment: A case report.

BACKGROUND: Hepatoid adenocarcinoma of the lung (HAL) is an extremely rare malignant tumor, and many patients with HAL exhibit high levels of alpha-fetoprotein (AFP) expression. Currently, there is no standardized treatment strategy for advanced HAL and its prognosis is poor. CASE SUMMARY: We report a 55-year-old man with unresectable AFP-related HAL. The largest cross-sectional area of the mass in the upper lobe of the left lung at the beginning of treatment was 8.46 cm × 6.53 cm. The patient's serum AFP level was 9283 ng/mL. The mass increased in size to 8.86 cm × 8.21 cm after two courses of platinum-based combination chemotherapy and immunotherapy, and serum AFP reached its highest level (71232.2 ng/mL). The patient was treated with sorafenib (400 mg twice daily, per os). Forty days later, the mass was reduced to 5.63 cm × 5.29 cm and serum AFP level dropped to 786.8 ng/mL. The patient achieved partial remission for > 9 mo with sorafenib and an excellent biomarker response, as well as survival > 13 mo, which is among the longest reported for unresectable stage IV HAL. CONCLUSION: This is the first report to document successful treatment of unresectable AFP-related HAL with single-agent sorafenib after multiline therapy.

Sodium houttuyfonate protects against cardiac injury by regulating cardiac energy metabolism in diabetic rats.

Diabetic cardiomyopathy is a diabetic complication with complicated pathophysiological changes and pathogenesis and difficult treatment. Sodium houttuyfonate is the adduct of sodium bisulfite and houttuynin, the main volatile component in Houttuynia cordata Thunb, possesses a variety of activities including multiple interventions on inhibiting ventricular remodeling. The study aims to explore effect of sodium houttuyfonate on diabetic myocardial injury and its underlying mechanisms. The diabetes model was established by intraperitoneal injection of streptozotocin at a dose of 85 mg/kg. By intragastric administration for 26 days, sodium houttuyfonate (50 and 100 mg/kg/d) reversed the abnormal serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, improved the abnormal levels of serum aspartate aminotransferase and brain natriuretic peptide, reduced electrocardiogram P-R and QRS interval extension, accelerated the heart rate, decreased serum malondialdehyde content, up-regulated the myocardial energy metabolism including elevated the contents of ATP, ADP, total adenine nucleotides and phosphocreatine in myocardium, decreased AMP/ATP ratio, elevated myocardial Ca2+-Mg2+-ATPase activity, and down-regulated the mRNA expressions of AMP protein activation kinase α2 (AMPK-α2) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). In a conclusion, these results suggest that sodium houttuyfonate can improve cardiac energy metabolism disorder caused by diabetes by increasing cardiac Ca2+-Mg2+-ATPase activity and regulating AMPK signaling pathway, and then attenuates cardiac injury caused by hyperglycemia. In addition, sodium houttuyfonate also has the effects of anti-oxidation and improving abnormal levels of blood lipid.

Metastatic urothelial carcinoma harboring ERBB2/3 mutations dramatically respond to chemotherapy plus anti-PD-1 antibody: A case report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) targeting the programmed death (PD)-1 pathway have substantially changed the clinical management of metastatic urothelial carcinoma (mUC); however, the response rate remains low. There are ongoing efforts to identify robust biomarkers that can effectively predict the treatment response to ICIs. Previous studies have suggested that ERBB2/3 mutations are associated with the efficacy of ICIs in gallbladder carcinoma. CASE SUMMARY: We present a 59-year-old man with mUC harboring ERBB2/3 mutations (in-frame insertion of ERBB2 and ERBB3 amplification), negative PD-ligand 1 expression, and low tumor mutation burden. He received anti-PD-1 antibodies and paclitaxel as second-line treatment. After two cycles of treatment, the lung metastases had significantly shrunk, achieving good partial remission. After six cycles of combination therapy, the patient received sindilimab 200 mg once every 3 wk as maintenance monotherapy. At the last follow-up, the patient continued to exhibit a partial response and progression-free survival for as long as 19 mo. CONCLUSION: ERBB2/3 mutations may represent a predictive biomarker for selecting a subgroup of mUC patients who will benefit from ICIs.

Chrysin Improves Glucose and Lipid Metabolism Disorders by Regulating the AMPK/PI3K/AKT Signaling Pathway in Insulin-Resistant HepG2 Cells and HFD/STZ-Induced C57BL/6J Mice.

Natural products with minor side effects have been reported to be an effective adjuvant therapy for glucose and lipid metabolism disorders. Chrysin, a flavone, has a wide range of physiological effects, such as antioxidant, anti-inflammatory, anti-diabetes, anti-hyperlipidemia, and hepatoprotective. This study was designed to explore the effects and mechanism of chrysin on metabolic syndrome using insulin-resistant HepG2 cells and HFD/STZ-induced C57BL/6J mice. The results indicated that chrysin significantly decreased insulin resistance, oxidative stress, inflammation, and liver injury. In addition, chrysin improved glycogen synthesis and fatty acid oxidation and inhibited gluconeogenesis and fatty acid synthesis by regulating GSK3ß, G6Paes, PEPCK, SREBP1, FAS, and ACC1. Furthermore, the results of western blot and real-time PCR experiments demonstrated that chrysin modulated glucose and lipid metabolism through the AMPK/PI3K/AKT signaling pathway. Treatment with the AMPK inhibitor verified that AMPK activation is positively correlated with chrysin activity on glycolipid metabolism. This study confirms that chrysin is a potential treatment for glucose and lipid metabolism disorders.

Chalcomoracin inhibits cell proliferation and increases sensitivity to radiotherapy in human non-small cell lung cancer cells via inducing endoplasmic reticulum stress-mediated paraptosis.

Chalcomoracin (CMR) is a kind of Diels-Alder adduct extracted from the mulberry leaves. Recent studies showed that CMR has a broad spectrum of anticancer activities and induces paraptosis in breast cancer and prostate cancer cells. In this study, we investigated the effects of CMR against human non-small cell lung cancer cells and the underlying mechanisms. We found that CMR dose-dependently inhibited the proliferation of human lung cancer H460, A549 and PC-9 cells. Furthermore, exposure to low and median doses of CMR induced paraptosis but not apoptosis, which was presented as the formation of extensive cytoplasmic vacuolation with increased expression of endoplasmic reticulum stress markers, Bip and Chop, as well as activation of MAPK pathway in the lung cancer cells. Knockdown of Bip with siRNA not only reduced the cell-killing effect of CMR, but also decreased the percentage of cytoplasmic vacuoles in H460 cells. Moreover, CMR also increased the sensitivity of lung cancer cells to radiotherapy through enhanced endoplasmic reticulum stress. In lung cancer H460 cell xenograft nude mice, combined treatment of CMR and radiation caused greatly enhanced tumor growth inhibition with upregulation of endoplasmic reticulum stress proteins and activation of pErk in xenograft tumor tissue. These data demonstrate that the anticancer activity and radiosensitization effect of CMR result from inducing paraptosis, suggesting that CMR could be considered as a potential anticancer agent and radiation sensitizer in the future cancer therapeutics.

Complete response to trastuzumab and chemotherapy in recurrent urothelial bladder carcinoma with HER2 gene amplification: A case report.

BACKGROUND: Targeted treatments may greatly affect the natural history of urothelial carcinoma based on their pharmacokinetics. A phase II trial has explored the combination of cytotoxic chemotherapy with the anti-HER-2 monoclonal antibody trastuzumab in selected patients with metastatic bladder cancer, but it failed. CASE SUMMARY: Here, we report a case of recurrent urothelial bladder carcinoma (UBC) in a patient who has undergone three operations, and further illuminate its diagnosis and treatment. The diagnosis of UBC was rendered according to the pathological indices. Next-generation sequencing on formalin fixed paraffin-embedded (FFPE) tissue was also performed and suggested HER2 gene amplification in the FFPE tissue. Based on HER2 gene amplification in FFPE, the patient was treated with chemotherapy in combination with trastuzumab after his third surgery. Fortunately, the patient got a clinically complete remission to trastuzumab for 34 mo. CONCLUSION: There is not enough clinical evidence for incorporating trastuzumab in routine treatment of UBC. This case hinted that recurrent UBC patients with HER2 gene amplification may benefit from targeted trastuzumab. Further studies are needed to further investigate the status of HER2 gene and better determine trastuzumab in the management of UBC.

Idiopathic adulthood ductopenia with elevated transaminase only: A case report.

BACKGROUND: Idiopathic adulthood ductopenia (IAD) is a chronic cholestatic liver disease of unknown etiology that usually presents as unexplained jaundice. It is characterized by adult onset, lack of autoantibodies, inflammatory bowel disease and loss of interlobular bile ducts. CASE SUMMARY: This case presents a 27-year-old woman with elevation of transaminases and alkaline phosphatase without clinical symptoms. Five years ago, the patient had abnormal transaminases but no cholestasis. Three months before admission, physical examination revealed an increase in transaminases. Oral hepatoprotective drugs did not show any significant improvement, and she was admitted to hospital for further diagnosis and treatment. Liver biopsy confirmed IAD. After about 2 wk of ursodeoxycholic acid treatment, serological and histological examination showed a significant response. CONCLUSION: IAD is a manifestation of cholestasis, but also may be an abnormal increase in transaminase in the early stage.

The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer.

OBJECTIVES: FOLFIRINOX (FFX) or abraxane plus gemcitabine (AG)-based chemotherapy is used widely as firstline treatment for patients with pancreatic cancer. However, their use in the elderly is discouraged because of adverse events. More clinical data about the therapeutic response and tolerability to FFX or AG in elderly patents (over 70 years old) are required. METHODS: Patients with advanced pancreatic cancer (n = 203; 131 metastatic pancreatic cancer patients (MPC) and 72 locally advanced pancreatic cancer patients (LAPC)) were treated using modified-FFX (mFFX) or AG and mFFX sequentially. The patients were grouped according to their age, patients below 70 years old and patients above 70 years old. The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and adverse events were compared between the groups. RESULTS: The ORRs in the elderly and in patients below 70 were similar (30.0% versus 32.3%). The median OS and PFS were also similar between the groups (mOS 13.3 m vs 12.7 m, p = 0.729, HR 0.874 (95% CI 0.5310 to 1.438); mPFS mPFS 10.6 m vs 10.3 m, p = 0.363, HR 0.800 (95% CI 0.4954 to 1.293)). However, the elderly patients suffered a higher incidence of severe adverse events (50% vs. 28.3%). CONCLUSIONS: These data could provide guidance for chemotherapy use in elderly patients with advanced pancreatic cancer. Age did not affect treatment outcome; however, supportive treatment is very important for elderly patients receiving chemotherapy.

Risk of Immune-Related Pancreatitis in Patients with Solid Tumors Treated with Immune Checkpoint Inhibitors: Systematic Assessment with Meta-Analysis.

We performed a systematic review and meta-analysis to determine the risk of immune-related pancreatitis associated with the treatment by immune checkpoint inhibitors (ICIs) for solid tumors. Eligible studies were selected from multiple databases including phase II/III randomized controlled trials (RCTs) with ICIs in solid tumor patients. The data were analyzed with Stata version 12.0 software. After excluding ineligible studies, a total of 15 clinical trials were considered eligible for the meta-analysis, which included 9099 patients. Compared with chemotherapy or placebo, the risk ratio (RR) for all-grade lipase elevation after CTLA-4 inhibitor treatment was 1.05 (95% confidence interval (CI): 1.01-2.24, p = 0.047). However, the risk for pancreatitis after ICI treatment in any subgroup was not significantly higher than that after control therapy. In addition, compared with ipilimumab/nivolumab alone, the RR for all-grade and high-grade lipase elevation under combination treatment of nivolumab and ipilimumab was 6.43 (95% CI: 1.43-28.99, p = 0.015) and 6.44 (95% CI: 1.39-29.79, p = 0.017), respectively, and the RR for all-grade amylase elevation under combination treatment was 6.08 (95% CI: 1.51-24.44, p = 0.011). Our meta-analysis has demonstrated that both CTLA-4 inhibitors alone and combination treatment of nivolumab and ipilimumab could increase the risk of amylase or lipase elevation, but not significantly increase the risk of pancreatitis when compared with controls.

The risk of immune-related endocrine disorders associated with anti-PD-1 inhibitors therapy for solid tumors: A systematic review and meta-analysis.

BACKGROUND: We performed a systematic review and meta-analysis to evaluate the risk of immune-related endocrine disorders associated with PD-1 inhibitors therapy for solid tumors. METHODS: An Embase and PubMed search through December 6, 2017, using the following keywords was performed: immune-related endocrine disorders, and PD-1 inhibitors, etc. The data were analyzed using R 3.4.3 (R Project) and the metafor package. Patients treated with chemotherapy alone were used as control for the purpose of comparison. RESULTS: A total of 12 clinical trials including 5577 patients were found eligible for the meta-analysis. Compared with chemotherapy, the risk ratios of all-grade endocrine disorders are 13.89, (95% CI: 5.35-36.05, p < 0.001) for nivolumab therapy, and 9.85, (95% CI: 5.65-17.17, p < 0.001) for pembrolizumab therapy. The risk of all-grade hypothyroidism and hyperthyroidism incidence was increased for nivolumab therapy (hypothyroidism: RR 10.07, 95% CI: 3.37-30.11, p < 0.001; hyperthyroidism: RR 4.29, 95% CI: 1.13-16.30, p = 0.034) and for pembrolizumab therapy (hypothyroidism: RR 7.73, 95% CI: 3.86-15.49, p < 0.001; hyperthyroidism: RR 5.09, 95% CI: 2.36-10.97, p < 0.001). There was a significant increase in the risk of grade 1-5 endocrine disorders incidence for ipilimumab-nivolumab combination therapy (versus ipilimumab, RR 3.20, 95% CI: 2.08-4.91, p < 0.001; versus nivolumab, RR 2.54, 95% CI: 1.70-3.80, p < 0.001). CONCLUSIONS: Both nivolumab and pembrolizumab therapy could result in a higher risk of all-grade immune-related endocrine disorders than chemotherapy. Nivolumab and ipilimumab combination therapy could result in an even higher risk of all-grade immune-related endocrine disorders than ipilimumab or nivolumab alone. Awareness of these side effects could guide clinicians to better manage the patients treated with anti-PD-1 inhibitors therapy for solid tumors.

Breast metastasis of gastric signet-ring cell carcinoma.

Metastatic breast involvement from extra-mammary neoplasms is unusual with a low incidence of 0.5% to 1.2% in clinical practice, 2.7% in cytological series, and 1.7% to 6.6% in autopsy series of all breast malignancies. Nearly 500 cases have been reported in small series and case reports. Gastric carcinoma rarely metastasizes to the breast. There are only 38 cases reported in PubMed. In this study, we present a case report of a 49-year-old woman who was diagnosed with right breast metastasis from a gastric carcinoma and undertake a literature review to pay attention to the diagnosis, treatment, and the prognosis of the disease.

Design and synthesis of 28-hydroxy protopanaxadiol as a novel probe template.

To explore the antitumour mechanism of 20(S)-protopanaxadiol (PPD) while maintaining its uncovered pharmacological active site 3-hydroxyl, 28-hydroxy protopanaxadiol (17), a small molecular probe template of PPD was first designed and synthesised based on the Baldwin's reaction. Thus, 28-hydroxyl of 17 was built successfully as a derivatized site of molecular probe's functional and report groups. The important intermediates and final product were confirmed by ESI-MS and nuclear magnetic resonance spectra with good yield. These studies provided a valuable basis for probe research of PPD.

Pharmacokinetics and safety of cyclophosphamide and docetaxel in a hemodialysis patient with early stage breast cancer: a case report.

BACKGROUND: Standardized chemotherapy used in cancer patients with severe kidney insufficiency is ineffective. Although there are some pharmacokinetic studies on cyclophosphamide in kidney insufficiency patients, to the best of our knowledge, the pharmacokinetics and safety of combination of cyclophosphamide and docetaxel as postoperative chemotherapy in a patient with early stage breast cancer undergoing hemodialysis is unclear thus far. CASE PRESENTATION: The patient received regular TC regimen (cyclophosphamide 600 mg/m2, docetaxel 75 mg/m2). She underwent hemodialysis 48 h after chemotherapy. Blood samples at multiple time-points were collected for determination of plasma levels of cyclophosphamide and docetaxel. Pharmacokinetic analyses indicated that compared with the reference data, the in vivo half-life (66.96 h) and drug exposure (150%) of cyclophosphamide significantly increased; however, pharmacokinetic parameters of docetaxel was unaffected. Patient developed grade I thrombocytopenia and grade III leukopenia without any other severe adverse reactions. In total, four cycles of treatment were completed. After the chemotherapy, the patient received tamoxifen as endocrine therapy for one and a half years. No recurrence was reported. CONCLUSION: These results suggest that the standard TC regimen is mostly safe and could be used as postoperative adjuvant chemotherapy for hemodialysis patients with early stage breast cancer.

Efficacy and safety profile of celecoxib for treating advanced cancers: a meta-analysis of 11 randomized clinical trials.

PURPOSE: Evidence on the benefits of combining celecoxib, a cyclooxygenase-2 inhibitor, in treating advanced cancer is still controversial. This study aimed to establish the efficacy and safety profile of celecoxib in treating advanced cancers. METHODS: The PubMed, Embase, and Cochrane databases and abstracts from the American Society of Clinical Oncology and European Society for Medical Oncology were searched for reports dated up to January 31, 2014, to find relevant randomized clinical trials. The outcomes included overall response rate (ORR), 1-year mortality, progression-free survival, overall survival, and toxicities. Fixed-effects meta-analytical models were used when indicated, and between-study heterogeneity was assessed. Subgroup analysis was conducted according to cancer type, treatment pattern, and treatment line. FINDINGS: A total of 11 randomized clinical trials consisting of 2570 patients with advanced cancer were included in the final meta-analysis. Addition of celecoxib to the treatment regimen significantly increased the ORR (pooled risk ratio [RR] = 1.20; 95% CI, 1.06-1.36; P = 0.005) but had no effect on 1-year mortality (RR = 1.02; 95% CI, 0.92-1.13; P = 0.68). Subgroup analysis found that the ORR results were significant with non-small cell lung cancer (RR = 1.29; 95% CI, 1.08-1.54; P = 0.005), colorectal cancer (RR = 1.32; 95% CI, 1.02-1.72; P = 0.037), chemotherapy treatment (RR = 1.22; 95% CI, 1.07-1.39; P = 0.003), and first-line treatment (RR = 1.22; 95% CI, 1.07-1.38; P = 0.003). However, celecoxib increased the risk of cardiovascular events (RR = 1.78; 95% CI, 1.30-2.43; P < 0.001) and anemia (RR = 1.88; 95% CI, 0.95-3.74; P = 0.071). IMPLICATIONS: Celecoxib is beneficial in the treatment of advanced cancers but with increased risk of cardiovascular events. Benefit versus harm needs to be carefully considered when celecoxib is recommended in patients with advanced cancers.

ω-3 polyunsaturated fatty acids inhibit the proliferation of the lung adenocarcinoma cell line A549 in vitro.

ω-3 polyunsaturated fatty acids (n-3 PUFA), in particular the marine-derived forms eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been demonstrated to affect cancer cell replication, the cell cycle and cell death. Epidemiological studies have also suggested diets rich in n-3 PUFA were inversely correlated with the development of cancer. In the present study, we explored the effects of DHA and EPA on the proliferation activity and apoptosis of the human lung adenocarcinoma cell line A549. A methyl thiazolyl tetrazolium (MTT) assay was used to detect cell proliferation, apoptosis was detected by flow cytometry and morphological analysis was determined by fluorescence microscopy and transmission electron microscopy. A549 cells were treated with different doses of DHA (40, 45, 50 and 55 µg/ml) or EPA (45, 50, 55 and 60 µg/ml) for 24, 48 and 72 h. The results demonstrated that DHA and EPA significantly suppressed the proliferation of A549 cells and induced apoptosis of A549 cells in a dose- and time-dependent manner. The apoptotic phenomenon was also confirmed by fluorescence microscopy and transmission electron microscopy. Furthermore, compared with the control, the formation of autophagosomes was clearly enhanced in DHA­ or EPA-treated cells. In conclusion, DHA and EPA inhibited the proliferation of A549 cells and induced cell apoptosis and autophagy, which may provide new safe and effective options for the treatment of lung cancer in the future.

Phase II trial of gefitinib in pretreated Chinese women with advanced non-small-cell lung cancer.

A phase II clinical trial was performed to evaluate the efficacy and safety of gefitinib on pretreated Chinese female non-small-cell lung cancer (NSCLC) patients. Chinese female patients with locally advanced or metastatic NSCLC who failed at least one platinum-based chemotherapy received gefitinib monotherapy (250 mg/day) between April 2002 and January 2010. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS) and progression-free survival (PFS). Of the 40 evaluable female patients, the ORR was 62.5%. All patients have responded with one (2.5%) complete response, 24 (60%) partial response, 12 (30%) stable disease, and 3 (7.5%) progressive disease. The OS and PFS were 20 months (95% CI: 11.9-28 months) and 13 months (95% CI: 8.0-17.9 months), respectively. Survival (OS and PFS) were longer in patients with good performance status and in patients older than 65 years (P < 0.05). The most frequently observed toxicities were rash/dry skin (80%), diarrhea (42.5%), and vomiting/anorexia (32.5%). Four patients developed grade 3 toxicities (rash and diarrhea) but did not require either dose reduction or discontinuation. Gefitinib is a highly effective and well-tolerated agent for Chinese women with pretreated advanced NSCLC.

Phase II study of FOLFIRI regimen in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.

PURPOSE: To evaluate the efficacy and safety of FOLFIRI regimen in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin. METHODS: The FOLFIRI regimen consisted of intravenous infusion of irinotecan 180 mg/m(2) on day 1 plus leucovorin (LV) 400 mg/m(2) on day 1 plus 5-fluorouracil (5-FU) 400 mg/m(2) bolus on day 1 plus 46-hour intravenous infusion of 5-FU 2,400 mg/m(2), every 2 weeks as one cycle. The main selection criterion for this study was the advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin. RESULTS: Of the 57 evaluable patients for efficacy, 4 (7.5%) had a partial response, 36 (67.9%) had stable disease, and 13 (24.5%) had progressive disease. Median progression-free survival was 4.8 months (95% CI 3.9-5.7 months), and median overall survival was 7.8 months (95% CI 13.1-16.5 months). Safety analysis was based on the data of 57 evaluable patients. The most frequently observed grade 3 or 4 toxicities were neutropenia 16 (27.8%), nausea/vomiting 7 (12.3%), and diarrhea 1 (1.8%). CONCLUSION: FOLFIRI regimen is effective and well tolerated in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin in Chinese population.

Quantitative profiles of the mRNAs of ER-alpha and its novel variant ER-alpha36 in breast cancers and matched normal tissues.

OBJECTIVE: The novel estrogen receptor-alpha (ER-alpha) variant ER-alpha36 is reported to be functional in the estrogen signaling pathway and is related to tamoxifen resistance in breast cancer. However, ER-alpha36 tends to be a favorable factor for survival in patients without tamoxifen therapy. To investigate the mechanisms behind this paradox, we determined the differences between the transcriptional profiles of ER-alpha36 and full-length ER-alpha (ER-alpha66) in breast cancers and matched normal tissues. METHODS: We analyzed ER-alpha36 and ER-alpha66 messenger RNA (mRNA) levels in 74 pairs of breast cancers and matched normal tissues using a real-time quantitative polymerase chain reaction (PCR) assay, and correlated the results with their clinicopathological characteristics. RESULTS: Breast cancers expressed lower ER-alpha36 mRNA levels than matched normal tissues regardless of their ER-alpha66 expression status. Down-regulation of ER-alpha36 mRNA was correlated with local progression, lymph node metastasis, and advanced cancer stage. The level of ER-alpha66 mRNA was lower in ER-alpha negative breast cancers compared with matched normal tissues. No differences in ER-alpha66 mRNA levels were observed during cancer progression. CONCLUSION: Down-regulation of ER-alpha36 is associated with carcinogenesis and progression of breast cancer.

A Phase II trial of oxaliplatin, folinic acid, and 5-fluorouracil (FOLFOX4) as first-line chemotherapy in advanced colorectal cancer: a China single-center experience.

PURPOSE: To evaluate the efficacy and toxicity of leucovorin (LV) plus 5-fluorouracil (5-FU) combined with oxaliplatin every 2 weeks on previously untreated advanced colorectal cancer patients in Chinese population. PATIENTS AND METHODS: Forty-nine patients were enrolled to receive, entirely as inpatients, 2-weekly cycles of oxaliplatin 85 mg/m2 i.v. over 2 hours on Day 1, together with leucovorin 200 mg/m2 over 2 hours, 5-FU 400 mg/m2, bolus, followed by a 22-hours infusion of 5-FU at 600 mg/m2 Days 1-2 (FOLFOX4) every 2 weeks. Treatment was given until progression or unmanageable toxicity. In all, 49 patients received ≥ 1 oxaliplatin dose and a median of 7 treatment cycles (range 1∼27 cycles). RESULTS: Of the 45 eligible patients, 1 complete response (CR) and 18 partial responses (PRs) were observed for an overall response rate of 42.2 percent (95 percent confidence interval 26∼56 percent). Median progression-free survival was 7.2 months (6.4∼8.0) and median overall survival was 14.8 months (13.1∼16.5). Six patients (12.2 percent) reported Grade 3∼4 neutropenia. Thirty-one patients (62.3 percent) experienced Grade 1∼3 neurotoxicity and only 5 patients (10.2 percent) experienced Grade 3 neurotoxicity. CONCLUSION: In our experience, FOLFOX4 regimen is active and well tolerated in patients with previously untreated advanced colorectal cancer in Chinese population.

A phase II trial of gemcitabine plus carboplatin in advanced transitional cell carcinoma of the urothelium.

BACKGROUND: Recent studies have demonstrated the effectiveness of cisplatin-based combinations in patients with advanced transitional cell carcinoma(TCC) of the urothelium. Concern over cisplatin toxicity instigated a search for alternative regimens. The aim of the study was to evaluate the activity and tolerability of gemcitabine plus carboplatin combination as first-line treatment in patients with advanced transitional cell carcinoma of the urothelium. METHODS: Patients with advanced TCC were treated with gemcitabine 1200 mg/m2 on days 1 and 8 and carboplatin area under the concentration-time curve(AUC) 5 on day 1 every 21 days. RESULTS: Out of 41 patients, thirty-nine were evaluable for efficacy and 41 for toxicity. A median of 5 cycles (range 1-6) was administered. Overall response rate was 46.2% (95% confidence interval: 32-65%) including 10.3% complete responses and 35.9% partial responses. The median time to progression and median overall survival were 7.5 months (95% confidence interval: 6.6-8.4 months) and 13.6 months (95% confidence interval: 10.2-17.0 months), respectively. Grade 3/4 neutropenia, anemia and thrombocytopenia were observed in 36.6%, 26.8, and 24.4% of patients, respectively. Non-hematological toxicity was generally mild. Grade 3 vomiting occurred in 1 (2.4%) patients. CONCLUSION: The gemcitabine plus carboplatin combination is active in advanced TCC with acceptable toxicity and needs to be evaluated further and compared with other non-cisplatin-containing regimens. TRIAL REGISTRATION: ISRCTN88259320.