Adenocarcinoma ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Adenocarcinoma, Bronchiolo-Alveolar ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Adenocarcinoma, Papillary ; metabolism ; pathology ; Cadherins ; metabolism ; Diagnosis, Differential ; Genes, erbB-1 ; genetics ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Lymphatic Metastasis ; Mucin-1 ; metabolism ; Mutation ; Neoplasm Invasiveness ; beta Catenin ; metabolism

Clear cell carcinoma (CCC) of the ovary is known to show poorer sensitivity to chemotherapeutic agents and to be associated with a worse prognosis than the more common serous adenocarcinoma or endometrioid adenocarcinoma. To improve the survival of patients with ovarian CCC, the deeper understanding of the mechanism of CCC carcinogenesis as well as the efforts to develop novel treatment strategies in the setting of both front-line treatment and salvage treatment for recurrent disease are needed. In this presentation, we first summarize the mechanism responsible for carcinogenesis. Then, we highlight the promising therapeutic targets in ovarian CCC and provide information on the novel agents which inhibit these molecular targets. Moreover, we discuss on the cytotoxic anti-cancer agents that can be best combined with targeted agents in the treatment of ovarian CCC.
Adenocarcinoma, Clear Cell/drug therapy/*etiology/metabolism ; Antineoplastic Agents/therapeutic use ; Female ; Forecasting ; Humans ; Neoplasm Recurrence, Local/prevention & control ; Ovarian Neoplasms/drug therapy/*etiology/metabolism

OBJECTIVETo investigate the relationship between the pathologic responses and histologic type, grade, the expression of ER, PR and HER2 and their changes in breast carcinoma before and after neoadjuvant chemotherapy (NAC).

METHODSTwo-hundred and nine cases of breast cancer with NAC were analyzed and clinical, pathologic data were evaluated based on the Miller and Payne ( MP) grading system. The expression of ER, PR and HER2 in the cancers before and after NAC were detected by immunohistochemistry (MaxVision method). SPSS 15.0 software was used to conduct statistical analysis.

RESULTS(1) Pathologic responses to the NAC were graded as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases); (2) The expression of ER in core needle biopsy had related negatively to the pathologic response (chi2 = 33.083, P = 0.001). However, the histologic type, grade, ER and PR status, and HER2 expression in surgically-removed specimens had not related to the pathologic response (P>0.05); (3) After NAC, the pathologic type and grade changed in 6. 8% (9/132) and 34.9% (30/86) of the cases, and the rates of changes in the expression of ER, PR and HER2 were 42.4% (75/177), 55.4% (98/177) and 26.6% (46/173) , respectively. Only the expression of HER2 had significant difference between before and after neoadjuvant chemotherapy (P = 0.049). The changes in other data had no relationship with the pathologic response (P>0.05).

CONCLUSIONSAnalysis of core needle biopsy can provide important information to predict the pathologic responses to the NAC. The pathologic appearance, grade, ER, PR and HER2 in breast carcinoma may change after NAC. It is necessary to examine the histologic type, grade and the expression of ER, PR and HER2 after NAC once more.

Adenocarcinoma, Mucinous ; drug therapy ; metabolism ; pathology ; surgery ; Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Lobular ; drug therapy ; metabolism ; pathology ; surgery ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Staging ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo investigate the predictive value of P53, Ki-67, HER2 protein detection in neoadjuvant chemotherapy for adenocarcinoma of gastroesophageal junction (AGEJ).

METHODSPreoperative biopsy specimens and clinical data of 72 patients of locally advanced Siewert II AGEJ between June 2010 and December 2013 were reviewed. All the patients received SOX scheme neoadjuvant chemotherapy, and were divided into effective group (complete response plus partial response) and ineffective group (stable disease plus progressive disease). Expressions of above 3 proteins were detected by immunohistochemistry in all the patients before neoadjuvant chemotherapy. The relationship between various proteins and efficacy of chemotherapy was analyzed by univariate and logistic multivariate regression analyses.

RESULTSAll the 72 patients successfully completed 2 cycles of SOX neoadjuvant chemotherapy, among them, 5 cases (6.9%) with complete response, 30 cases (41.7%) with partial response, 31 cases (43.1%) with stable disease, 6 cases (8.3%) with progressive disease, including 35 cases in effective group and 37 cases in ineffective group. Compared with ineffective group, the positive expression rate of P53 was significantly reduced (25.0% vs. 45.9%, P=0.020), and that of Ki-67 significantly increased (77.1% vs. 43.2%, P=0.003), however, there was no significant difference in the expression rate of HER2 between the two groups (P>0.05). Multivariate analysis showed that Ki-67 was the independent predictive factor for the efficacy of neoadjuvant chemotherapy (P=0.015). Spearman rank correlation showed that Ki-67 expression was positively correlated with HER2 expression (r=0.259, P=0.028), but P53 expression was not correlated with Ki-67 or HER2 (r=0.140, 0.042, P=0.240, 0.725, respectively).

CONCLUSIONSSOX neoadjuvant chemotherapy is safe and effective for AGEJ, especially for patients with depressed expression of P53 and elevated expression of Ki-67, which both may be used as reference for the prediction of chemotherapy efficacy. There is no correlation between P53 and Ki67 proteins, so combined detection may improve the predictive value.

Adenocarcinoma ; diagnosis ; drug therapy ; Esophageal Neoplasms ; diagnosis ; drug therapy ; Esophagogastric Junction ; pathology ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Neoadjuvant Therapy ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Tumor Suppressor Protein p53 ; metabolism

Adenocarcinoma ; complications ; drug therapy ; metabolism ; Aged ; Antineoplastic Agents ; therapeutic use ; Fusion Proteins, bcr-abl ; metabolism ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; etiology ; metabolism ; Male ; Organoplatinum Compounds ; therapeutic use ; Stomach Neoplasms ; drug therapy ; metabolism

BACKGROUNDHistone deacetylase inhibitors can regulate gene expression through modulation of the degree of acetylation of histone and non-histone, thus affecting cell proliferation, survival and chemosensitivity. Histone deacetylase inhibitors combined with paclitaxel may enhance the inhibitory effect of drugs on lung cancer cells. This study aimed to observe the effect of trichostatin A (TSA)/paclitaxel on the proliferation and apoptosis in human A549 lung adenocarcinoma cells, and to investigate its mechanism.

METHODSA549 cells were cultured in Dulbecco modified Eagle's medium (DMEM) in the presence of paclitaxel and the histone deacetylase inhibitor TSA, and the growth curve was obtained by trypan-blue exclusion assay and cell count. Apoptosis was assessed using Hoechst 33258 staining and flow cytometry analysis, and cell cycle was detected by flow cytometry analysis. The proteins poly ADP-ribose polymerase (PARP), caspase-3, survivin, and tubulin acetylation were detected by Western blotting.

RESULTSA significant reduction of proliferation was observed in A549 lung adenocarcinoma cells treated by paclitaxel or TSA. Combined treatment with TSA/paclitaxel caused the greatest inhibition of cell proliferation. The combined treatment with TSA and paclitaxel induced more severe apoptosis, and significantly more cells were arrested in G2/M phase (P < 0.05) then with a single drug. Using Western blotting, we demonstrated that treatment with TSA/paclitaxel led to synergistic increase in acetylated tubulin, PARP, caspase-3, and reduced the expression of survivin.

CONCLUSIONTSA and paclitaxel have a synergistic activity that can inhibit cell growth and induce apoptosis.

Acetylation ; Adenocarcinoma ; drug therapy ; pathology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Hydroxamic Acids ; pharmacology ; Lung Neoplasms ; drug therapy ; pathology ; Paclitaxel ; pharmacology ; Tubulin ; metabolism

In recent years, the number of advanced non-small cell lung cancer (NSCLC) patients has gradually increased, and the treatment methods have also been significantly increased. However, there are no standard treatment plans at home and abroad for third-line and above patients who are refractory to targeted therapy epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) or chemotherapy. The clinical treatment effect is also not satisfactory. Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. ALTER0303 trail, phase III study has demonstrated that Anlotinib significantly prolonged overall survival (OS) and progression-free survival (PFS) in advanced NSCLC patients as 3rd line treatment.Here we report a case of advanced lung adenocarcinoma harboring KRAS mutation treated with Anlotinib.
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Adenocarcinoma ; drug therapy ; enzymology ; genetics ; pathology ; Adenocarcinoma of Lung ; Aged ; Antineoplastic Agents ; therapeutic use ; Humans ; Indoles ; therapeutic use ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; pathology ; Male ; Mutation ; Proto-Oncogene Proteins p21(ras) ; genetics ; metabolism ; Quinolines ; therapeutic use

OBJECTIVETo investigate the inhibitory effect of arsenic trioxide, aspirin and their combination on the growth of human gastric adenocarcinoma SGC-7901 graft in nude mice.

METHODSThirty-one model nude mice with transplanted tumor of human gastric adenocarcinoma SGC-7901 were established successfully by fixing tumor tissue under the left axillary subcutaneously. They were randomly divided into 4 groups and treated respectively with normal saline (control group, n = 7), aspirin (Asp group, n = 8), arsenic trioxide (AT group, n = 8), and AT +Asp (combined treated group, n = 8), medicated by intraperitoneal injection for 14 successive days. All mice were sacrificed 48 h after the final medication, the transplanted tumor mass volume and weight were measured to calculate the tumor inhibition rate, and changes of tumors and tissues of heart, liver, and kidney, etc were observed. Moreover, expressions of proliferation associated protein Ki67 and apoptosis inhibitory protein Bcl-2 were detected by immunohistochemical SP method, and expression of apoptosis associated protein Bax was detected by Western blotting.

RESULTSAfter terminating the medication, in the combined treated group the tumor volume and weight were significantly lower than those in the control group (P < 0.05) and the tumor weight was lower than that in the AT and Asp groups (both P < 0.05). The volume inhibition rate was 59.12% in the AT group, 47.60% in the Asp group, and 76.70% in the combined treated group, and the weight inhibition rate in them 35.60%, 45.44% and 63.90%, respectively. Immunochemical staining showed that as compared with the control group, expressions of Ki67 and Bcl-2 were down-regulated in all the three treated groups to some extent (all P < 0.05), and significant difference was also shown in comparison of the two indices between the combined treated group with the other two treated groups (P < 0.05). The expression of Bax was higher in the combined treated group than in other groups (all P < 0.05).

CONCLUSIONCombined use of AT and Asp has certain cooperative effect in inhibiting the growth of gastric carcinoma cells without obvious toxic-side effects.

Adenocarcinoma ; drug therapy ; Animals ; Arsenicals ; pharmacology ; Aspirin ; pharmacology ; Humans ; Ki-67 Antigen ; metabolism ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Oxides ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stomach Neoplasms ; drug therapy ; bcl-2-Associated X Protein ; metabolism

BACKGROUND: There are significantly interindividual variations of the expression level of nuclear factor erythroid-2-related factor 2 (Nrf2) and/or Kelch-like ECH-associated protein 1 (Keap1) in our previous studies. It has been proven that Nrf2 or Keap1 is related to resistance of chemotherapeutic drugs and/or epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, the expression of Nrf2 and Keap1 in lung adenocarcinoma patients with different "driver gene" is not clear. The aim of this study is to investigate the protein expression level of Nrf2 and Keap1 in lung adenocarcinoma and to elucidate the correlation between Nrf2 or Keap1 expression and the status of EGFR gene mutation and to determine the effects of Nrf2 and Keap1 on the patients. METHODS: Immunohistochemical analysis of Nrf2 and Keap1 in tumor specimens was performed in a total of 104 lung adenocarcinoma patients with the status of EGFR gene mutations or EGFR wide-type. RESULTS: The Nrf2 positive rate was 71.2% and Keap1 high expression rate was 34.6% in 104 patients. The Nrf2 positive rate significantly correlated with gender, stage and status of EGFR gene mutation (P<0.05), but not with age, smoking, differentiation and subtype of lung adenocarcinoma (P>0.05). The high expression of Keap1 was not significantly correlated with gender, age, smoking, differentiation, subtype of lung adenocarcinoma and status of EGFR gene mutation (P>0.05). The progression -free survival (PFS) and overall survival (OS) of the patients treated by EGFR-TKIs were significantly correlated with the expression level of Nrf2, but not with Keap1. The PFS and OS of the patients with Nrf2 high expression were significantly shorter than the patients with low/negative expression (P<0.05). Furthermore, Nrf2 high expression was the independent predictive factor for EGFR-TKIs induced PFS and OS (P<0.05). CONCLUSIONS The Nrf2 positive rate significantly correlated with the status of EGFR gene mutation in lung adenocarcinoma. The Nrf2 high expression significantly correlated with PFS and OS of EGFR-TKIs. Therefore, Nrf2 may be a biomarker for predicting response of EGFR-TKIs and a potential target for overcoming resistance of EGFR-TKIs.
Adenocarcinoma ; drug therapy ; genetics ; metabolism ; pathology ; Adenocarcinoma of Lung ; Adult ; Aged ; Aged, 80 and over ; ErbB Receptors ; genetics ; metabolism ; Female ; Humans ; Kelch-Like ECH-Associated Protein 1 ; genetics ; metabolism ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Mutation ; NF-E2-Related Factor 2 ; genetics ; metabolism ; Neoplasm Staging ; Protein Kinase Inhibitors ; therapeutic use ; Young Adult

OBJECTIVETo explore the clinicopathological characteristics and prognostic factors of primary appendiceal adenocarcinoma.

METHODSThe clinicopathological data of 42 patients with primary appendiceal adenocarcinoma treated in the Cancer Hospital of Chinese Academy of Medical Sciences between March 1994 and October 2009 were retrospectively analyzed. The survival analysis was conducted using Kaplan-Meier method. The factors influencing survival were analyzed using univariate (Log-rank) and multivariate (Cox) models.

RESULTSA total of 42 patients (29 female and 13 males, median age 56 years) with appendiceal adenocarcinoma were included in this study. Of them, 26 (61.9%) were mucinous adenocarcinoma, 12 (28.6%) were intestinal-type adenocarcinoma and 4 (9.5%) were signet cell carcinoma. 18 patients underwent curative resection, 20 patients received cytoreductive surgery, and 4 patients underwent biopsy only. Thirty patients received systemic chemotherapy (5-Fu-based regimens). One patient who died of postoperative pulmonary embolism on day 8 was excluded from the survival analysis. The overall 1-, 3-, and 5-year survival rate was 80.3%, 46.0% and 38.3%, respectively. Univariate analysis revealed that presence of symptoms of acute appendicitis, curative resection, histological grade, histological subtype, preoperative CEA level, systematic chemotherapy, and stage were all significant factors affecting the survival. Multivariate analysis showed that the preoperative CEA level (P = 0.01), histological grade (P = 0.001), and stage (P = 0.001) were independent prognostic factors.

CONCLUSIONSHigh level of CEA, G2/3 grade, and advanced stage are associated with poor prognosis in patients with primary appendiceal adenocarcinoma.

Adenocarcinoma ; drug therapy ; metabolism ; pathology ; surgery ; Adenocarcinoma, Mucinous ; drug therapy ; metabolism ; pathology ; surgery ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Appendectomy ; methods ; Appendiceal Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoembryonic Antigen ; metabolism ; Carcinoma, Signet Ring Cell ; drug therapy ; metabolism ; pathology ; surgery ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Young Adult