OBJECTIVETo analyze the clinicopathological characteristics of patients with anaplastic lymphoma kinase (ALK) rearrangements in lung adenocarcinoma, and the clinical therapy and prognosis of the patients.

METHODSClinicopathological data of 34 cases of ALK-positive patients treated in the Beijing Chest Hospital from 2005 to 2014 were reviewed. The expression of ALK proteins in the resected tumors was detected by immunohistochemistry, and EGFR mutations were examined by polymerase chain reaction and a direct DNA sequencing method.

RESULTSAmong the 34 patients, 20 were male and 14 were female, the median age was 49, and 11 were smokers and 23 were never smokers. The clinical stages of the patients were stage IA in 5 patients, IB in one patient, IIA in two patients, IIIA in 16 patients, IIIB in 5 patients, IV in 4 patients, and one patient of unknown stage. ALK-positive tumors showed strong granular staining in cell cytoplasm by immunohistochemistry. Forteen patients were solid predominant subtype with mucin production, 10 of acinar predominant subtype, 6 of papillary predominant subtype, 3 of micropapillary predominant subtype, and one was of colloid variant. There were 18 cases with mucin production, 6 cases had signet-ring cell morphology, and 10 cases showed cribriform pattern. Only one patient had coexistence of ALK rearrangement and EGFR mutation (L858R at exon 21). Of the 34 patients, 24 patients were followed up. The median follow up of the 24 patients was 11.0 months (1.7-48.7 months).

CONCLUSIONSALK-positive tumors as a molecular subtype of lung adenocarcinoma have distinct clinicopathological features. The histological findings of ALK-positive tumors are characterized by solid predominant subtype with mucin production, acinar predominant subtype, signet-ring cells and cribriform structures. They were rarely co-mutated with EGFR mutation.

Adenocarcinoma ; enzymology ; pathology ; therapy ; Exons ; Female ; Gene Rearrangement ; Genes, erbB-1 ; Humans ; Immunohistochemistry ; Lung Neoplasms ; enzymology ; pathology ; therapy ; Male ; Middle Aged ; Mucins ; biosynthesis ; Mutation ; Neoplasm Proteins ; genetics ; Polymerase Chain Reaction ; Prognosis ; Receptor Protein-Tyrosine Kinases ; genetics ; Sequence Analysis, DNA

OBJECTIVETo investigate the value of the liquid-based cytology (LBC) of brushing specimens obtained via fiberoptic bronchoscopy for clinical diagnosis of lung cancer.

METHODSWe retrospectively analyzed the LBC cases in our hospital from January 2011 to May 2012, and evaluate its role in the diagnosis of lung cancer.

RESULTSThe clinical data of a total of 4 380 cases were reviewed and 3 763 of them had histopathological or clinical follow-up results (including 3 306 lung cancer cases and 457 benign lesion cases). The sensitivity, specificity, and accuracy of LBC diagnosis for lung cancer were 72.4% (2 392/3 306), 99.3% (454/457) and 75.6% (2 846/3 763), respectively. Of the 1 992 lung cancer cases diagnosed by brushing LBC, 528 cases (26.5%) were failed to take forceps biopsy and 113 cases (5.7%) showed negative forceps biopsy results. The accurate rate of subtyping of LBC for non-small cell carcinoma and small cell carcinoma was 99.0% (1 487/1 502) (P < 0.001). Take the resection histopathology as gold standard, the accurate rates of subtyping squamous cell carcinoma, adenocarcinoma and small cell carcinoma by LBC were 95.6% (351/367), 95.6% (351/367) and 100% (367/367), respectively, (P < 0.001). The accurate rates of subtyping of squamous cell carcinoma, adenocarcinoma and small cell carcinoma by forceps biopsy were 97.0% (293/302), 97.4% (294/302) and 99.7% (301/302), respectively, (Kappa = 0.895, P < 0.001). There was no significant difference in subtyping respectively between forceps biopsy and brushing LBC (P > 0.05).

CONCLUSIONSFiberoptic bronchoscopic brushing liquid-based cytology can significantly improve the detection rate of lung cancer, and have a high specificity and accurate rate of subtyping. It is an effective tool for the diagnosis and subtyping of lung cancer.

Adenocarcinoma ; pathology ; Biopsy ; instrumentation ; methods ; Bronchi ; Bronchoscopy ; methods ; Carcinoma, Non-Small-Cell Lung ; pathology ; Carcinoma, Small Cell ; pathology ; Carcinoma, Squamous Cell ; pathology ; Humans ; Lung Neoplasms ; pathology ; Retrospective Studies ; Sensitivity and Specificity ; Small Cell Lung Carcinoma ; pathology ; Surgical Instruments

OBJECTIVETo investigate the expression of osteopontin (OPN) splice variant mRNA, including the three isoforms OPN-A, OPN-B, and OPN-C, to explore its correlation with clinicopathologic features in gastric cancer, and to elucidate their role in tumor invasion and distant metastasis of gastric cancer.

METHODSThe expression of OPN-A, OPN-B and OPN-C mRNA were detected by real-time reverse transcriptase-polymerase chain reaction in 66 gastric cancer tissues. The relationship between the expression of OPN-A, OPN-B and OPN-C mRNA and clinicopathologic features of gastric cancer was analyzed.

RESULTSThe expression of OPN-C mRNA in the gastric cancer tissue was 3.21-fold higher than that in peritumoral mucosal tissue, showing a significant difference between them (P < 0.001). OPN-C mRNA expression was correlated with the depth of tumor invasion, tumor diameter, lymph node meatastasis, distant meatastasis and had no correlation with differentiation grades. The low expression of OPN-C mRNA was correlated with long survival benefit (P = 0.03). The expression of OPN-A and OPN-B mRNA had no significant relationship with clinicopathologic features of gastric cancer.

CONCLUSIONSOne of the isoform of osteopontin (OPN) OPN-C mRNA is overexpressed in gastric cancer. The overexpression of OPN-C mRNA may reflect the progression and is associated with the prognosis of gastric cancer. OPN-C mRNA may have value as a prognostic biomarker in gastric cancer. However, the expression of OPN-A and OPN-B are not correlated with the progression and metastasis of gastric cancer.

Disease Progression ; Gastric Mucosa ; metabolism ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Proteins ; genetics ; Osteopontin ; genetics ; Prognosis ; Protein Isoforms ; genetics ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Stomach Neoplasms ; genetics ; mortality ; pathology

OBJECTIVETo explore the associations between the genetic variations in the SDC2 gene and overall survival and risk of radiation esophagitis in patients with esophageal squamous cell carcinoma (ESCC).

METHODSEleven functional haplotype-tagging single nucleotide polymorphisms (htSNPs) of SDC2 were genotyped in 296 ESCC patients who received radiotherapy alone, and had different response and esophagitis. The associations between genotypes and risk of esophagitis were measured by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for sex, age, tumor location, staging, radiotherapy mode and total radiation dose. The hazard ratios (HRs) were estimated using Cox proportional hazards regression model.

RESULTSThe median survival time (MST) of these patients was 14 months. Of them, 260 (87.8%) had died until the last date of follow-up of 30 June, 2014. Clinical stage (stage IV vs. stage II) and total radiation dose (≥ 60 Gy vs. < 60 Gy) influence the overall survival time of the patient significantly. Cox proportional hazards regression model analysis showed that the subjects with rs61599409 T allele had an decreased hazard ratio as compared with those with C allele (adjusted HR = 0.82, 95% CI, 0.66-1.02), but the difference was not statistically significant (P = 0.071). The rest 10 htSNPs were not associated with the overall survival of ESCC patients treated with radiotherapy. Among this set of patients, 160 (54.1%) suffered from radiation esophagitis. We found that rs17788084 A > T SNP in the 3'-untranslational region of SDC2 was associated with esophagitis risk, with the OR being 0.48 (95% CI = 0.28-0.85, P = 0.011) for the TA or TT genotype compared with the AA genotype.

CONCLUSIONSThese results suggest that rs17788084 genetic variation in SDC2 is associated with risk of radiation esophagitis and might serve as a potential biomarker for personalized radiotherapy of ESCC.

Alleles ; Carcinoma, Squamous Cell ; mortality ; pathology ; radiotherapy ; Esophageal Neoplasms ; mortality ; pathology ; radiotherapy ; Esophagitis ; genetics ; Genetic Variation ; Genotype ; Haplotypes ; Humans ; Odds Ratio ; Polymorphism, Single Nucleotide ; Proportional Hazards Models ; Radiation Injuries ; genetics ; Radiotherapy Dosage ; Risk ; Survival Analysis ; Syndecan-2 ; genetics ; Time Factors

OBJECTIVETo explore the feasibility of preparation of a mouse model of orthotopic colon cancer by injecting tumor cell suspension into mesenteric triangle of the cecum.

METHODSTwenty SPF 8-week old BALB/c mice (male:female = 1:1) were used in this study. The mouse caecum was exposed by laparostomy, and suspension of mouse colon adenocarcinoma CT26. WT cells was injected into the mesenteric triangle of cecum for preparation of a mouse model of orthotopic colon cancer.

RESULTSMouse orthotopic colon cancer was developed by injection of tumor cell suspension into mesenteric triangle of the cecum showing a successful rate of 100%, without intestinal obstruction, and the liver, spleen, diaphragm and mesenteric lymph nodes metastasis rates were high in all the 20 experimental mice.

CONCLUSIONSThe establishment of mouse models of orthotopic colon cancer by injection of tumor cell suspension into the mesenteric triangle is a simple, rapid, and easy to master procedure, causing less damage to the colon wall, safe and with less trauma to the mice. This method may provide an ideal mouse model of orthotopic colon cancer for the study of pathogenesis as well as liver metastasis mechanisms of colon cancer.

Adenocarcinoma ; pathology ; secondary ; Animals ; Cecal Neoplasms ; pathology ; Cecum ; Colonic Neoplasms ; pathology ; Disease Models, Animal ; Feasibility Studies ; Female ; Liver Neoplasms ; secondary ; Lymphatic Metastasis ; Male ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; methods

OBJECTIVETo investigate the effect of CAL-101, a selective inhibitor of PI3Kδ, in combination with bortezomib on the proliferation and apoptosis in human mantle cell lymphoma cell lines Z138, HBL-2 and Jeko-1 in vitro, to explore its mechanisms and provide the foundation for effective treatment strategies against mantle cell lymphoma.

METHODSMTT assay was applied to detect the inhibitory effects of CAL-101 and bortezomib either alone or combined on Z138, HBL-2 and Jeko-1 cells. Calcusyn software was used to analyze the synergistic cytotoxicity. Western blot was used to detect the expression of PI3K-p110σ and p-Akt, Akt, p-ERK and ERK proteins after the cells were exposed to different concentrations of CAL-101. Flow cytometry was employed to assess the apoptosis rate. NF-κB kit was used to determine the changes of location of NF-κB P65, and Western blot was applied to detect the level of caswpase-3 and the phosphorylation of Akt in different groups.

RESULTSCAL-101 and BTZ inhibited the proliferation of Z138, HBL-2 and Jeko-1 cells in a dose- and time-dependent manner. CAL-101/BTZ combination induced significantly synergistic cytotoxicity in the MCL cells. The results of Western blot assay showed that CAL-101 significantly blocked the phosphorylation of Akt and ERK in the MCL cell lines. In addition, CAL-101 combined with BTZ induced pronounced apoptosis (P < 0.01). For example, after the Z138 cells exposed to the drugs for 48 h, the apoptosis rates of the control, CAL-101, BTZ and CAL-101 + BTZ groups were: (2.6 ± 1.8)%, (40.0 ± 3.0)%, (34.0 ± 1.0)%, and (67.4 ± 1.0)%, respectively; and when drug treatment was given to HBL-2 cells over 96 h, the apoptosis rates of these four cell groups were (7.4 ± 0.6)%, (30.7 ± 5.7)%, (12.0 ± 1.0)%, and (85.0 ± 4.0)%, respectively. The combination therapy contributed to the enhanced inactivity of nuclear factor-κB (NF-κB) and Akt inactivation in the MCL cell lines (P < 0.05), however, the casepase-3 activity was up-regulated.

CONCLUSIONSThe combination of CAL-101 and bortezomib is muchmore effective in inhibiting proliferation and promoting apoptosis of mantle cell lymphoma cell lines (Z138, HBL-2 and Jeko-1), which may be mediated through inhibiting PI3K/Akt signaling pathway and the transcription of NF-κB.

Antineoplastic Agents ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Apoptosis ; drug effects ; Blotting, Western ; Boronic Acids ; Bortezomib ; pharmacology ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Class Ia Phosphatidylinositol 3-Kinase ; antagonists & inhibitors ; Dose-Response Relationship, Drug ; Drug Synergism ; Formazans ; Humans ; Lymphoma, Mantle-Cell ; drug therapy ; pathology ; MAP Kinase Signaling System ; drug effects ; NF-kappa B ; metabolism ; Neoplasm Proteins ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Purines ; administration & dosage ; pharmacology ; Pyrazines ; Quinazolinones ; administration & dosage ; pharmacology ; Signal Transduction ; Software ; Tetrazolium Salts

OBJECTIVETo study the molecular mechanism of cisplatin to enhance the ability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in reversing multidrug resistance in vincristine-resistant human gastric cancer SGC7901/VCR cells.

METHODSMTT assay was used to measure the 50% inhibiting concentration (IC₅₀) and cell survival in SGC7901 and SGC7901/VCR cells after different treatments. SGC7901/VCR cells were treated with different concentrations of DDP, different concentrations of TRAIL alone or in combination, and then the mRNA and protein levels of several genes were determined by RT-PCR, RT-qPCR and Western-blot analysis. After targeted silencing with specific siRNA and transfection of recombinant plasmid c-myc into the SGC7901/VCR cells, the mRNA and protein levels of DR4, DR5 and c-myc were determined by RT-PCR and Western-blot analysis.

RESULTSAfter combined treatment with TRAIL and DDP of the SGC7901/VCR cells, the IC₅₀ of VCR, DDP, ADM, and 5-Fu treatment was significantly decreased compared with the control group or TRAIL-treated group (P < 0.05). After treatment with 0, 10, 50 ng/ml TRAIL in combination with 0.4 µg/ml DDP, the SGC7901/VCR cells showed significantly higher activation of caspase 3, down-regulation of DNA-PKcs/Akt/GSK-3β signaling pathway, and higher inhibition of MDR1(P-gp) and MRP1 than those treated with TRAIL alone (P < 0.01 for all). The mRNA and protein levels of DR4, DR5, c-myc were significantly decreased after silencing c-myc with specific siRNA in the SGC7901/VCR cells (P < 0.01 for all), and were significantly increased after transfection of recombinant plasmid c-myc into the SGC7901/VCR cells (P < 0.01 foe all). After the treatment with 10 ng/ml TRAIL, 0.25 µg/ml DDP + 10 ng/ml TRAIL and 0.5 µg/ml DDP + 10 ng/ml TRAIL, the relative expression level of c-myc protein in the SGC7901/VCR cells was 0.314 ± 0.012, 0.735 ± 0.026, and 0.876 ± 0.028, respectively, and the relative expression of cytochrome C was 0.339 ± 0.036, 0.593 ± 0.020 and 0.735 ± 0.031, respectively, and the relative expression levels of DR4, DR5, active-caspase 3 and active-caspase 9 in the SGC7901/VCR cells were also increased along with increasing DDP concentrations.

CONCLUSIONSThe activation of DNA-PKcs/Akt/GSK-3β signaling pathway and high expression of MDR1 and MRP1 play an important role in the multi-drug resistance properties of SGC7901/VCR cells. After combining with TRAIL, DDP can enhance the expression of DR4 and DR5 through up-regulating c-myc and enhancing the activation of caspase 3 and caspase 9 by facilitating mitochondrial release of cytochrome C. It may be an important molecular mechanism of DDP-induced sensitization of TRAIL to reverse the multidrug resistancein SGC7901/VCR cells.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; pharmacology ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cisplatin ; administration & dosage ; pharmacology ; Down-Regulation ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Fluorouracil ; administration & dosage ; pharmacology ; Formazans ; Genes, myc ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Inhibitory Concentration 50 ; Multidrug Resistance-Associated Proteins ; metabolism ; Neoplasm Proteins ; metabolism ; Plasmids ; Proto-Oncogene Proteins c-myc ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; pharmacology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Stomach Neoplasms ; drug therapy ; pathology ; TNF-Related Apoptosis-Inducing Ligand ; administration & dosage ; pharmacology ; Tetrazolium Salts ; Transfection ; methods

Adenocarcinoma ; metabolism ; pathology ; Humans ; Stomach Neoplasms ; metabolism ; pathology ; alpha-Fetoproteins ; metabolism

OBJECTIVEObesity has been shown to be an indicator of poor prognosis for patients with primary breast cancer. The aim of this study was to clarify the effect of obesity on Chinese women with breast cancer.

METHODSThis is a retrospective analysis of 1699 breast cancer patients. We evaluated the effect of body mass index (BMI) on disease-free survival (DFS) and overall survival (OS) in these patients. BMI was obtained before surgery. Obesity was defined as a BMI ≥ 24. Kaplan-Meier analysis and Log rank test were employed to perform survival analysis. The impact of different characteristics on survival was assessed by using Cox proportional-hazards regression model.

RESULTSIn total 635 (37.4%) patients were obese, while 1 064 (62.6%) were non-obese. Comparing the tumor characteristics in the two groups, the BMI ≥ 24 group showed a higher rate of older age (P < 0.001), postmenopausal status (P < 0.001), increased risk of lymph node metastasis (P = 0.001) and less chances of accepting breast conservation surgery (P = 0.012). The median follow-up time was 16 months, and the estimated 16-months DFS was 98.1% for non-obese and 95.0% for obese patients (P = 0.007), the estimated 16-months OS was 99.4% for non-obese and 98.4% for obese patients (P = 0.004). The multivariate analysis indicated that obesity is an independent prognostic factor for OS and DFS in breast cancer patients.

CONCLUSIONSOur findings suggest that obesity is associated with a poorer outcome in Chinese female patients with breast cancer.

Body Mass Index ; Breast Neoplasms ; epidemiology ; China ; epidemiology ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Obesity ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Analysis

OBJECTIVEMyoepithelial carcinoma (MC) is a rare malignant neoplasm of the salivary gland. The aim of this study was to analyze the diagnosis, treatment and prognosis of MC of the parotid gland.

METHODSThe clinicopathological data of 17 cases of MC of the parotid gland treated in our hospital from 1999 to 2013 were analyzed retrospectively. Of all the 17 patients, 9 cases received radical surgery only, 5 cases received postoperative radiotherapy, 2 cases received preoperative radiotherapy, and one case received chemotherapy. The survival rate was calculated by Kaplan-Meier analysis.

RESULTSAmong the 17 patients, 11 patients had post-operative recurrence (11/17, 64.7%), Of these 11 cases, 5 cases (45.5%) had recurrence within one year after the first operation. During the follow-up for 12-180 months (median 50 months), six cases died (two patients died of distant metastases and 4 cases died of local recurrence). The overall 1-year, 2-year and 5-year survival rates were 94.1%, 74.2% and 64.9%, and the overall 1-year, 2-year and 5-year recurrence-free survival rates were 70.6%, 48.1% and 40.1%, respectively.

CONCLUSIONSRadical surgery is the main treatment modality for myoepithelial carcinoma of the parotid gland. For the patients with extensive lesions or after palliative surgery, adjuvant radiotherapy or chemotherapy might be helpful. However, its therapeutic efficacy remains to be proved.

Carcinoma ; diagnosis ; therapy ; Combined Modality Therapy ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Myoepithelioma ; diagnosis ; therapy ; Neck Dissection ; Neoplasm Recurrence, Local ; Parotid Gland ; pathology ; Parotid Neoplasms ; diagnosis ; therapy ; Prognosis ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate