ABSTRACT
BACKGROUND: AT-rich interactive domain-containing protein 1A (ARID1A) is a subunit of the mammary SWI/SNF chromatin remodeling complex and a tumor suppressor protein. The loss of ARID1A been observed in several types of human cancers and associated with poor patient prognosis. Previously, we have reported that ARID1A protein was rapidly ubiquitinated and destructed in gastric cancer cells during DNA damage response. However, the ubiquitin e3 ligase that mediated this process remains unclear. MATERIALS AND METHODS: The interaction between ARID1A and ß-TRCP was verified by co-immunoprecipitation (Co-IP) assay. The degron site of ARID1A protein was analyzed by bioinformatics assay. Short hairpin RNAs (shRNAs) were used to knockdown (KD) gene expression. RESULTS: Here we show that DNA damage promotes ARID1A ubiquitination and subsequent destruction via the ubiquitin E3 ligase complex SCFß-TRCP. ß-TRCP recognizes ARID1A through a canonical degron site (DSGXXS) after its phosphorylation in response to DNA damage. Notably, genetic inactivation of the Ataxia Telangiectasia Mutated (ATM) kinase impaired DNA damage-induced ARID1A destruction. CONCLUSIONS: Our studies provide a novel molecular mechanism for the negative regulation of ARID1A by ß-TRCP and ATM in DNA damaged gastric cancer cells.
ABSTRACT
BACKGROUND: To date, no single colorectal cancer (CRC) screening strategy has been determined to be applicable worldwide. In China, a CRC screening protocol that combines double fecal immunochemical tests (FITs) and a high-risk factor questionnaire (HRFQ) as the first stage of screening and colonoscopy as the second stage of screening (scenario A) was adapted by the Chinese Ministry of Health in 2006. However, applying this CRC screening protocol nationally remains difficult because its effectiveness and convenience are controversial. This study evaluated the effects of subitems of the CRC screening protocol in China. METHODS: CRC screening results (scenario A) from Jiashan County, China, (2007-2009) were used to analyze the detection rates of CRC and advanced neoplasms as well as the cost-effectiveness of the protocol. Scenario A was divided into scenarios B-G (by selecting some items at the first stage of screening) for analysis. RESULTS: Compared with scenario A, removing the whole HRFQ (scenario F) reduced advanced neoplasm and adenoma detections by 29.8 and 41.2%, respectively, whereas the whole HRFQ accounted for 10.1% of the total screening cost. Removing FITs (scenario G) reduced CRC, advanced neoplasm and adenoma detections by 71.8, 56.9 and 47.7%, respectively, and the costs per case of CRC and advanced neoplasm were 82.0 and 19.1% higher, respectively, than those in scenario A. In scenarios B-E (deleting some high-risk factor questions on the HRFQ), the odds ratios (ORs) of the detection rates and costs per CRC, advanced neoplasm, adenoma, and neoplasm case were near 1.00. Scenarios C and D reduced the high-risk population and total screening costs by less than 6.0 and 4.1%, respectively. Scenarios E and B (FITs and a personal history of cancer or colorectal adenoma were reserved) reduced the high-risk population by 17.6 and 24.2% and the total screening costs by 11.2 and 15.4%, respectively, while the numbers of CRC cases were not missed, and advanced neoplasms detected decreased by only 5 and 11%, respectively. CONCLUSION: The results of this study demonstrate that FITs and a personal history of colorectal adenoma are the most effective items in the Chinese CRC screening protocol.
Subject(s)
Colorectal Neoplasms/epidemiology , China/epidemiology , Colorectal Neoplasms/diagnosis , Early Detection of Cancer , Female , Humans , Male , Mass Screening , Odds Ratio , Public Health Surveillance , Risk FactorsABSTRACT
BACKGROUND: Salvage surgery has been recommended as the approach of choice for neck residue or recurrence of nasopharyngeal carcinoma (NPC) after primary radiotherapy (RT). This study aimed to assess the outcome and prognostic factors, options for different surgical methods, and the extent of neck dissection (ND) for patients. METHODS: NPC patients who had undergone RT and received salvage surgery for neck residue or recurrence from January 2001 to December 2011 were retrospectively analyzed. The overall survival (OS) rate was calculated by Kaplan-Meier method, and prognostic factors were determined by log-rank test and Cox regression analysis. RESULTS: In 153 cases, 96 cases have level I dissections. The metastasis rate was 20/153 (13.07%) for level I metastasis and 7/153 (4.58%) for parotid gland cases. The 3- and 5-year OS rate was 57.2 and 40.6%, respectively, and median survival time was 49 months. By univariate analysis, the age, rN staging, size of lymph nodes (LN), extra-capsular spread (ECS), and surgical procedure were significant prognostic factors. By multivariable analysis, the age, rN staging, and size of LN were significant prognostic factors. CONCLUSIONS: Salvage surgery is effective for neck failure of NPC after primary treatment, but patients with age >50 years, stage rN3, or LN >6 cm have poor prognosis.
Subject(s)
Nasopharyngeal Neoplasms/surgery , Neck Dissection , Neck/surgery , Neoplasm Recurrence, Local/surgery , Neoplasm, Residual/surgery , Salvage Therapy , Adolescent , Adult , Aged , Carcinoma , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/radiotherapy , Neck/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Staging , Neoplasm, Residual/pathology , Neoplasm, Residual/radiotherapy , Prognosis , Radiotherapy , Retrospective Studies , Survival Rate , Young AdultABSTRACT
In search of new compounds with strong antiproliferative activity and simple molecular structure, we designed a novel series of agents based on the 2-amino-3-alkoxycarbonyl/cyano-5-arylethylthiophene scaffold. The presence of the ethyl spacer between the 2',5'-dimethoxyphenyl and the 5-position of the thiophene ring, as well as the number and location of methoxy substitutents on the phenyl ring, played a profound role in affecting the antiproliferative activity. Among the synthesized compounds, we identified the 2-amino-3-cyano-[2-(2,5-dimethoxyphenyl)ethyl] thiophene 2c as the most promising derivative against a wide panel of cancer cell lines (IC50=17-130 nM). The antiproliferative activity of this compound appears to correlate well with its ability to inhibit tubulin assembly and the binding of colchicine to tubulin. Moreover 2c, as determined by flow cytometry, strongly induced arrest in the G2/M phase of the cell cycle, and annexin-V and propidium iodide staining indicate that cell death proceeds through an apoptotic mechanism that follows the intrinsic mitochondrial pathway.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Thiophenes/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Mice , Models, Molecular , Molecular Structure , Polymerization/drug effects , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Thiophenes/chemical synthesis , Thiophenes/chemistry , Tubulin/metabolismABSTRACT
Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignant tumor with a poor prognosis. The optimal disease staging system and treatment approaches have not yet been defined. This study aimed to evaluate the prediction of different staging systems for prognosis and treatment options of SCCE. We retrospectively accessed the clinicopathologic characteristics, treatment strategy, and prognosis of 76 patients diagnosed with primary SCCE between 2001 and 2011. The 1-, 2-, 3-, and 5-year overall survival rates were 58%, 31%, 19%, and 13%, respectively. Univariate analysis showed that the 2002 American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) classification (P = 0.002), Veterans Administration Lung Study Group (VALSG) stage (P = 0.001), predisposing factors (P < 0.001), T category (P = 0.023), and M category (P < 0.001) were prognostic factors for overall survival. Multivariate analysis showed that the 2002 AJCC TNM stage (P < 0.001) was the only independent prognostic factor for survival. The value of the area under the receiver operator characteristic (ROC) curve (AUC) of the 2002 AJCC TNM staging system was larger than that of VALSG staging system with regard to predicting overall survival (0.774 vs. 0.620). None of the single treatment regimens showed any benefit for survival by Cox regression analysis. Thus, the 2002 AJCC TMN staging system improved the prediction of SCCE prognosis; however, the optimal treatment regimen for SCCE remains unclear.
Subject(s)
Carcinoma, Small Cell/classification , Esophageal Neoplasms/classification , Neoplasm Staging/methods , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/pathology , Carcinoma, Small Cell/therapy , Cisplatin/administration & dosage , Combined Modality Therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Esophagectomy/methods , Etoposide/administration & dosage , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Paclitaxel/administration & dosage , Radiotherapy, High-Energy , Retrospective Studies , Societies, Medical , Survival Rate , United StatesABSTRACT
OBJECTIVE: To compare the performances of fecal occult blood quantitive testing instrument and colloidal gold strip method in colorectal cancer screening. METHODS: A representative random population of 9000 subjects aging between 40 and 74 years old were selected from Xuxiang, Haining city, Zhejiang province, by random cluster sampling method in year 2011. The fecal samples from each subject were separately detected by the two methods, namely fecal occult blood quantitive testing instrument and colloidal gold strip method. The positive result was standardized by hemoglobin concentration (HGB) ≥ 100 ng/ml under the application of quantitive testing instrument, or color-developing by colloidal gold strip method. The positive subjects from either method would be provided a further colonoscopy examination for pathological diagnosis. The positive rate and consistency of the two methods were compared, as well as the positive predictive value and population detecting rate of the colorectal cancer and adenoma. RESULTS: A total of 6475 (71.9%) subjects submitted their two fecal samples according to our requirement in 9000 subjects. There were separately 319 positive cases (4.9%) and 146 positive cases (2.3%) by the performances of fecal occult blood quantitive testing instrument and colloidal gold strip method, including 45 positive in both tests (Kappa = 0.168, 95%CI:0.119-0.217).184 out of the 319 positive cases (57.7%) in the test by quantitive testing instrument and 89 out of 146 positive cases (61.0%) in the test by colloidal gold strip method received the colonoscopy examination. There were no significant statistical differences between the two methods in the positive predictive value of colorectal cancer (P > 0.05) , developing adenoma and non-developing adenoma.However, the population detecting rate of the colorectal cancer and developing adenoma were higher in the test by quantitive testing instrument (26 cases, 0.402%) than it in the test by colloidal gold strip method (10 cases, 0.154%). The difference showed statistical significance (χ(2) = 7.131, P < 0.01). CONCLUSION: The performances of fecal occult blood quantitive testing instrument might be better than colloidal gold strip method in colorectal cancer screening. However, the results need to be further verified.
Subject(s)
Adenoma/diagnosis , Colorectal Neoplasms/diagnosis , Mass Screening/methods , Occult Blood , Adenoma/epidemiology , Adenoma/prevention & control , Adult , Aged , China/epidemiology , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/prevention & control , Feces , Female , Humans , Male , Middle AgedABSTRACT
Estrogen receptor (ER)-negative breast cancer cells are probably more aggressive with larger metastatic potential than ER-positive cells. Loss of ER in recurrent breast cancer is associated with poor response to endocrine therapy. G protein-coupled receptor 30 (GPR30) is expressed in half of ER-negative breast cancers. Tumor cell-derived heregulin-ß1 (HRG-ß1) is also found mainly in ER-negative cancer. In SkBr3 breast cancer cells that lack ER but express GPR30, HRG-ß1 upregulates mRNA and protein levels of GPR30 by promoting ErbB2-ErbB3 heterodimerization and activating the downstream MAPK-ERK signaling pathway. Moreover, GPR30 boosts HRG-ß1-induced migration and invasion of SkBr3 cells after combinative treatment with E2, 4-hydroxy-tamoxifen or the specific GPR30 agonist G-1, which are blocked by the specific GPR30 antagonist G-15 or the transfection with the small interfering RNA for GPR30. The ErbB2 inhibitor AG825 and the MEK1/2 inhibitor U0126 also partly inhibit the enhanced migration and invasion. Therefore, HRG-ß1-induced migration and invasion partly depend on the upregulation of GPR30 expression through activation of the ErbB2-ERK pathway in SkBr3 cells. The results of this study indicate that the crosstalk between GPR30 and HRGs signaling is important for endocrine therapy resistance and may provide a new therapeutic way to treat breast cancer.
Subject(s)
Breast Neoplasms/pathology , Cell Movement , Neuregulin-1/metabolism , Receptors, Estrogen/biosynthesis , Receptors, G-Protein-Coupled/biosynthesis , Breast Neoplasms/metabolism , Cell Line, Tumor , Female , Humans , MAP Kinase Signaling System , Mitogen-Activated Protein Kinase Kinases/metabolism , Neoplasm Invasiveness , Receptor, ErbB-2/metabolism , Receptor, ErbB-3/metabolism , Up-RegulationABSTRACT
Background: This study is aimed at identifying the important biomarkers associated with bone metastasis (BM) in breast cancer (BRCA). Methods: The GSE175692 dataset was used to detect significant differential expressed genes (DEGs) between BRCA samples with or without BM, and DEG-related pathways were then explored. Further, we constructed the protein-protein interaction (PPI) network on GEGs and filtered 5 vital nodes. We then performed the Cox regression, Kaplan-Meier analysis, nomogram, and ROC curve to filter the most significant prognosis genes. The GSE14020 and GSE124647 datasets were used to verify the expression and prognostic value of hub genes, respectively. Finally, the gene set enrichment analysis (GSEA) was performed to reveal the potential mechanism. Results: Totally, 74 DEGs were detected, which mainly correlated with infectious disease, signaling molecules, and interaction. The 5 important DEGs were then filtered, and the Cox regression further showed that 2 genes, including prominin 1 (PROM1) and C-C motif chemokine ligand 2 (CCL2), were related to the prognosis of BRCA metastasis patients. Especially, PROM1 presented a better prognostic performance on the survival probability of patients than CCL2. Verification analysis further confirmed the abnormal expression and significant prognostic influence of PROM1. Finally, GSEA revealed that PROM1 was negatively related to IGF1 and mTOR pathways in BRCA metastasis. Conclusion: PROM1 was an important biomarker associated with BRCA bone metastasis and affected the prognosis of metastatic BRCA patients. It may play a vital role in metastatic BRCA by negatively regulating IGF1 and mTOR pathways.
Subject(s)
Breast Neoplasms , AC133 Antigen/genetics , Biomarkers, Tumor/genetics , Breast Neoplasms/pathology , Computational Biology , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Ligands , Prognosis , TOR Serine-Threonine Kinases/metabolismABSTRACT
BACKGROUND/AIMS: To comprehensively understand the influence of laparoscopic resection on expressions of metastasis related genes in colorectal cancer by microarray. METHODOLOGY: Adjacent cancer tissues were obtained from the same patient with rectal cancer pre and post laparoscopic resection. The mRNA expressions of metastasis related genes were detected by GEArray Q Series human tumor metastasis gene array HS-007. The microarray results were verified by real-time PCR. Preclinical studies focusing on the effect of CO2 pneumoperitoneum on colorectal cancer metastasis over the last ten years were reviewed. RESULTS: Microarray analysis revealed that the expression of many metastasis related genes changed significantly post laparoscopic operation. Several metastatic mechanisms were activated including extracellular matrix degradation, cell adhesion, inflammation and angiogenesis. Meanwhile, some well known metastasis inhibition pathways were also activated, including NM23, PTEN and Thrombospondin. In the literature review there were inconsistent findings among reported experimental studies in terms of the effect of CO2 pneumoperitoneum on colorectal cancer metastasis. CONCLUSIONS: This microarray finding implies that laparoscopic resection produced no overwhelming adverse effect on the expressions of metastasis related genes in colorectal cancer. In view of the increasing follow-up results from a number of clinical trials, laparoscopic surgery with CO2 pneumoperitoneum appears to be safe.
Subject(s)
Colorectal Neoplasms/surgery , Laparoscopy/methods , Oligonucleotide Array Sequence Analysis , Aged , Colorectal Neoplasms/genetics , Humans , Male , Neoplasm Metastasis , Pneumoperitoneum, ArtificialABSTRACT
OBJECTIVE: To evaluate a colorectal cancer screening program by tumor detection rate and discussing its application values. METHOD: In total, 43 713 subjects were recruited in the screening program who were the registered people aged 40 - 74 in Xiacheng and Jiashan during year 2007 - 2009. The first screening involved questionnaire survey of colorectal cancer related risk factors and fecal occult blood test (FOBT), colonoscopy was performed when a positive result was observed in the first screening. If polyps were found during colonoscopy, biopsy and pathological diagnosis were carried out. The screening data were analyzed and the tumor detection rate was calculated according to age or sex. RESULTS: 6489 subjects (14.85%) belonged to the high risk group of colorectal cancer in the first screening, in which 4701 subjects finished complete colonoscopy. Finally, 569 colorectal neoplasm were diagnosed, the detection rate was 12.10% (95%CI: 11.17% - 13.04%). It included 52 colorectal cancer (1.11%, 95%CI: 0.81% - 1.41%), 183 advanced adenoma (3.89%, 95%CI: 3.34% - 4.45%), 334 non-advanced adenoma (7.10%, 95%CI: 6.37% - 7.84%). The highest detective rate was observed in male group that aged 70 - 74 (22.81%, 95%CI: 16.98% - 28.70%), the lowest detective rate was observed in female group aged 40 - 44 (2.49%, 95%CI: 0.79% - 4.20%). CONCLUSION: The current colorectal cancer screening program in China works well, but the revision of the program is necessary.
Subject(s)
Colorectal Neoplasms/prevention & control , Mass Screening/methods , Adult , Aged , Biopsy , China , Colorectal Neoplasms/diagnosis , Female , Humans , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
PURPOSE: To investigate the impact of a laparoscopic resection on the quality of life in rectal cancer patients. METHODS: This study included 135 patients (laparoscopic resection [LR] 65 cases and open resection [OR] 70 cases). The European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires were used to measure the quality of life before the operation, then 1 week, 3 months, and 1 year after the operation. RESULTS: Eleven (16.9%) patients underwent a conversion from laparoscopic to open surgery. The incision length and blood loss both decreased significantly in the LR group in comparison to the OR group (P < 0.05). Recovery of the gastrointestinal function, bladder function, and ambulation was more rapid in the LR group (P < 0.05). The patients in the LR group reported better global health status (33.3 vs 25.0, P < 0.001), body image (77.8 vs 66.7, P = 0.008), and less pain (33.3 vs 50. 0, P = 0.009) 1 week after operation. Better body image was reported in the LR group even 1 year after the operation (P < 0.05). Fewer financial difficulties were reported by patients in the LR group (P < 0.001). No significant differences were found between two groups on other scales. CONCLUSIONS: This study showed that the quality of life benefits due to minimally invasive laparoscopic surgery were evident only in the immediate postoperative period. A laparoscopic rectal resection therefore provided only better cosmetic benefit over the longer term.
Subject(s)
Colectomy/methods , Laparoscopy/methods , Quality of Life , Rectal Neoplasms/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Period , Preoperative Period , Prospective Studies , Rectal Neoplasms/psychology , Surveys and Questionnaires , Treatment OutcomeABSTRACT
BACKGROUND: This study aimed to assess the efficacy and safety of laparoscopic resection (LR) for rectal cancer. METHODS: A case-control study involving three Chinese medical centers was conducted. Rectal cancer patients undergoing LR were compared with open resection (OR) cases simultaneously from January 2004 to December 2005. Data were collected, and basic characteristics, conversion rate, recovery, complications, adjuvant therapy, and recurrence rate were compared. Analysis was by intention to treat. RESULTS: A total of 335 rectal cancer procedures (115 LR and 220 OR) met the inclusion criteria. The patients' basic characteristics were similar in the two groups (p>0.05). Total mesorectal excision was performed for 85.59% of the patients (201/235), who received anal sphincter preservation. Compared with OR, LR had a shorter incision length, less blood loss, and less need for transfusion, but the operation time was longer (p<0.05). No significant differences were observed between the two groups in positive rates of longitudinal resection margins, numbers of harvested lymph nodes, complication rates during operation and postoperation, and perioperative reoperation and morbidity rates (p>0.05). Postoperative parenteral narcotics were used less in LR than in OR (47.8% vs 62.7%; chi(2)=6.867; p=0.009). The median time until first flatus; resumption of diet, defecation, micturition, and ambulation; and discharge were reduced in LR (p<0.05). Conversion from LR to OR was required by 11.3% of the patients (13/115). The intraoperative complication rate was 30.8% for the patients who underwent conversion. The operation time and postoperative complication rate were the same as for LR alone (p>0.05). The local recurrence rate was 3.7% for the LR group and 4.9% for the OR group (chi (2)=0.209; p=0.647) during the 20-month median follow-up period. CONCLUSIONS: The findings showed that LR for rectal cancer was safe and effective, resulting in faster recovery and a similar complication rate compared with OR. Conversion did not alter the patients' outcomes.
Subject(s)
Colectomy/methods , Laparoscopy/methods , Rectal Neoplasms/surgery , China/epidemiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Morbidity/trends , Neoplasm Recurrence, Local/epidemiology , Retrospective Studies , Survival Rate/trends , Treatment OutcomeABSTRACT
OBJECTIVE: To screen out specifically-expressed serum protein markers in familial adenomatous polyposis (FAP) and to establish a serum protein fingerprint diagnostic model for distinguishing FAP from sporadic colorectal adenomas. METHODS: Serum samples were collected from 19 FAP cases and 16 sporadic colorectal adenomas with informed consent. Serum protein fingerprint profiles were detected by SELDI-TOF-MS with CM 10 protein chip to screen out FAP adenoma-related serum protein markers, and support vector machine (SVG) technique was used to establish the diagnostic model to distinguish FAP from sporadic colorectal adenomas. RESULTS: Six differently-expressed protein peaks (P < 0.01) were detected. Among them proteins of 5640, 3160, 4180 and 4290 m/z were highly expressed in FAP adenomas, and proteins of 3940 and 3400 m/z were highly expressed in sporadic colorectal adenomas. The accuracy of diagnostic model established with SVG to distinguish FAP adenomas and sporadic colorectal adenomas was 94.7% and 93.7%, respectively. CONCLUSION: SELDI-TOF-MS can be effectively used to screen out the differentially expressed serum protein markers in FAP adenomas and sporadic colorectal adenomas, and a diagnostic model build by SVG to distinguish them has been successfully established. Therefore, a useful breakthrough point for research on molecular mechanisms of FAP pathogenesis is provided.
Subject(s)
Adenoma/metabolism , Adenomatous Polyposis Coli/metabolism , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/metabolism , Gene Expression Profiling , Adenoma/genetics , Adenomatous Polyposis Coli/genetics , Adult , Aged , Colorectal Neoplasms/genetics , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Protein Array Analysis , Proteomics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
OBJECTIVES: To use surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) protein chip array technology to detect proteomic patterns in the serum of women with endometriosis; build diagnostic models; and evaluate their clinical significance. METHODS: Serum samples from women with endometriosis and healthy women were studied using SELDI-TOF-MS protein chip technology. For every matched pair, two-thirds of the samples were used to look for different patterns and one-third was used for cross-validation. RESULTS: Five potential biomarkers were found and the diagnostic system distinguished endometriosis from validation samples with a sensitivity of 91.7% and a specificity of 90.0%. CONCLUSION: This method shows great potential in identifying biomarkers to be used for endometriosis screening.
Subject(s)
Endometriosis/diagnosis , Neural Networks, Computer , Peptide Mapping , Proteomics , Uterine Diseases/diagnosis , Adolescent , Adult , Biomarkers/analysis , Biomarkers, Tumor/analysis , Endometriosis/blood , Female , Humans , Middle Aged , Protein Array Analysis/methods , Sensitivity and Specificity , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Uterine Diseases/bloodSubject(s)
Adenomatous Polyposis Coli/diagnosis , Adenomatous Polyposis Coli/surgery , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/surgery , Adenomatous Polyposis Coli/drug therapy , Adenomatous Polyposis Coli/genetics , Antineoplastic Agents/therapeutic use , Colectomy , Colorectal Neoplasms, Hereditary Nonpolyposis/drug therapy , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Mismatch Repair , Humans , Ileostomy , Peutz-Jeghers Syndrome/diagnosis , Peutz-Jeghers Syndrome/drug therapy , Peutz-Jeghers Syndrome/genetics , Peutz-Jeghers Syndrome/surgeryABSTRACT
OBJECTIVE: To investigate the effect of microRNA143 on cell proliferation and K-ras expression in colorectal carcinoma. METHODS: Northern blot was used to examine the expression of miR-143 in colorectal carcinoma and adjacent normal tissues. A miR-143 expression vector was constructed and transfected into a human colon adenocarcinoma cell line SW480. Cell proliferation was evaluated by MTT assay. RT-PCR and Western blot were used to examine the expression of K-ras oncogene in transfected cells. RESULTS: The level of mature miR-143 was lower in tumors compared with adjacent normal tissues in 81% of colorectal carcinoma specimens. In transfected cells, the increased accumulation of miR-143 inhibited the cell proliferation, and resulted in approximately 40.3% decrease of K-ras protein levels, but had no effect on level of K-ras mRNA. CONCLUSION: The increased accumulation of miR-143 inhibits the proliferation of transfected cells, and results in down-regulation of K-ras protein in colorectal carcinoma.
Subject(s)
Cell Proliferation , Colonic Neoplasms/pathology , MicroRNAs/metabolism , ras Proteins/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Cell Line, Tumor , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Down-Regulation , Genes, ras , Genetic Vectors , Humans , MicroRNAs/genetics , Plasmids , RNA, Messenger/metabolism , TransfectionABSTRACT
OBJECTIVE: To analyze the adenomatous polyposis coli (APC) gene mutations in familial adenomatous polyposis (FAP) in Chinese. METHODS: DNA was extracted from blood samples taken from 31 FAP families, and all exons of the APC gene were amplified with touch-down PCR. APC gene mutations were screened by denaturing high performance liquid chromatography followed by sequencing if abnormal profile was detected. RESULTS: Twelve categories of APC gene mutations were found in 15 FAP families (48.39%) including 4 novel mutations in coding region and 3 mutations in introns. The 4 novel mutations in coding region were frameshift mutations and located in codons 255, 677, 1192 and 1403 respectively. Most mutations were clustered in exon 15 of APC gene leading to frameshift and accounted for 86.67%. Others were nonsense mutations (13.33%). CONCLUSION: The mutation rate of the APC gene in this group of Chinese FAP families was about 48.39%, and 4 novel mutations were detected. Frameshift mutation was the major mutation type in Chinese FAP and mainly located in exon 15.
Subject(s)
Adenomatous Polyposis Coli/genetics , Chromatography, High Pressure Liquid/methods , Genes, APC/physiology , Exons/genetics , Female , Frameshift Mutation/genetics , Humans , Introns/genetics , Male , Mutation , Polymerase Chain ReactionABSTRACT
OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C), a biologically active fraction isolated from total ginsenosides, to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide (CTX). METHODS: Mice with myelosuppression induced by CTX were treated with PDS-C at a low- (20 mg/kg), moderate- (40 mg/kg), or high-dose (80 mg/kg) for 7 consecutive days. The level of peripheral white blood cell (WBC), neutrophil (NEU) and platelet (PLT) were measured, the histopathology and colony formation were observed, the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot. RESULTS: In response to PDS-C therapy, the peripheral WBC, NEU and PLT counts of CTX-induced myelosuppressed mice were significantly increased in a dose-dependent manner. Similarly, bone marrow histopathology examination showed reversal of CTX-induced myelosuppression with increase in overall bone marrow cellularity and the number of hematopoietic cells (P<0.01). PDS-C also promoted proliferation of granulocytic and megakaryocyte progenitor cells in CTX-treated mice, as evidenced by significantly increase in colony formation units-granulocytes/monocytes and -megakaryocytes (P<0.01). The enhancement of hematopoiesis by PDS-C appears to be mediated by an intracellular signaling pathway, this was evidenced by the up-regulation of phosphorylated mitogen-activated protein kinase (p-MEK) and extracellular signal-regulated kinases (p-ERK), and receptor tyrosine kinase (C-kit) and globin transcription factor 1 (GATA-1) in hematopoietic cells of CTX-treated mice (P<0.05). CONCLUSIONS: PDS-C possesses hematopoietic growth factor-like activities that promote proliferation and also possibly differentiation of hematopoietic progenitor cells in myelosuppressed mice, probably mediated by a mechanism involving MEK and ERK protein kinases, and C-kit and GATA-1 transcription factors. PDS-C may potentially be a novel treatment of myelosuppression and pancytopenia caused by chemotherapy.
Subject(s)
Antineoplastic Agents/adverse effects , Cyclophosphamide/adverse effects , Ginsenosides/therapeutic use , Hematopoiesis/drug effects , Myeloid Cells/pathology , Panax/chemistry , Pancytopenia/drug therapy , Saponins/pharmacology , Animals , Cell Proliferation/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , GATA1 Transcription Factor/metabolism , Ginsenosides/pharmacology , Mice , Mitogen-Activated Protein Kinase Kinases/metabolism , Myeloid Cells/drug effects , Pancytopenia/chemically induced , Pancytopenia/pathology , Phosphorylation/drug effects , Proto-Oncogene Proteins c-kit/metabolism , Up-Regulation/drug effectsABSTRACT
BACKGROUND: Pancreatic endocrine tumors (PETs) are rare and their surgical treatment is often debated. The purpose of this retrospective study was to analyze the diagnosis and surgical strategy of functioning and non-functioning PETs. METHODS: From May 1980 to March 2006, 36 patients with pancreatic endocrine tumors at the Second Affiliated Hospital of Zhejiang University were retrospectively studied. RESULTS: Among the 36 patients, 29 (81%) had functioning tumors, and 7 (19%) had nonfunctioning tumors. Ninety-two percent of insulinomas were benign, whereas 4 (57%) of nonfunctioning PETs were malignant. The size of functioning tumors was (2.3 +/- 0.3) cm, that of nonfunctioning tumors was less than (5.1 +/- 0.5) cm. The combination CT and transabdominal ultrasonography resulted in a diagnostic sensitivity of 84%. Thirty-three primary lesions were precisely located in 32 patients (89%). Atypical tumor resection was performed for 73% of functioning tumors, while typical pancreatectomy was performed for 6 (85%) of nonfunctioning tumors. Moreover, 5 liver resections and 1 lymph node dissection were performed. During the follow-up, fifteen complications occurred in 12 (36%) patients after operation. The 5-year survival rate for patients with benign tumors was 92% compared to 50% for those with malignant tumors. Surgical cure was achieved in 95% of patients with benign insulinomas. CONCLUSIONS: Surgical strategy for PETs depends on the size and location of the tumor and the risk of malignancy. The optimal surgical procedure is key to prevent postoperative complication. Radical resection including initial and metastatic lesion may benefit patients with malignant PETs.
Subject(s)
Pancreatic Neoplasms/surgery , Adolescent , Adult , Aged , Female , Humans , Insulinoma/diagnosis , Insulinoma/mortality , Insulinoma/surgery , Male , Middle Aged , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/mortality , Positron-Emission TomographyABSTRACT
OBJECTIVE: Microcapsule chemoembolism is a promising treatment of tumors. We describe a deep lingual arterial embolization of tongue carcinoma with microcapsuled carboplatinum. METHODS: Lingual artery cast specimens from cadavers were microscopically examined, and 78 patients with tongue cancer were recruited and treated with the deep lingual arterial embolization therapy. RESULTS: Microcapsule embolism occurred approximately at the fifth or sixth level of the deep lingual artery branches. The five-year survival rate was 88.5% (69 out of 78), and the ten-year survival rate 52.6% (41 out of 78). CONCLUSION: The deep lingual arterial embolization of tongue carcinoma with microcapsuled carboplatinum is an effective therapy to treat carcinoma in mid-margin or mid-body of the tongue.