[Correlation between prognostic nutritional index and pleural thickness with survival time of epithelial malignant pleural mesothelioma patients].

Objective: To explore the role of prognostic nutritional index (PNI) and pleural thickness in the prognostic evaluation of patients with epithelial malignant pleural mesothelioma (MPM) . Methods: In April 2022, a retrospective analysis was conducted on the data and laboratory data of 41 patients with epithelial MPM admitted to the cardiothoracic surgery department of Chuxiong Yi Autonomous Prefecture People's Hospital from January 2018 to May 2021. Univariate and multivariate analysis were used to evaluate the relationships between total survival time, clinical characteristics, PNI and pleural thickness in patients. Results: The 41 patients were mostly male (26 cases, 63.4%) , with a median age of 55 years old. The main clinical manifestations were chest pain (53.7%) , bloody pleural effusion (75.6%) , and chest pain combined with bloody pleural effusion (36.6%) . The median survival time of patients with different TNM stage, efficacy after 4 cycles of chemotherapy, PNI, maximum pleural thickness after chemotherapy (post max) , sum of post max in 3 zones after chemotherapy (post sum) were statistically different (χ(2)=3.89, 14.51, 15.33, 4.33, 12.05, P<0.05) . Compared with patients with high PNI and post sum<32.26 mm, MPM patients with low PNI and post sum≥32.26 mm have higher risk of death, and the differences were statistically significant (HR=1.52, 95%CI: 1.75-11.93, P=0.002; HR=1.70, 95%CI: 1.84-16.23, P=0.002) . Conclusion: PNI and post sum can be used to predict the prognosis of patients with epithelial MPM.

[Prognosis of adenoid cystic carcinoma of head and neck and risk factors for lung metastasis].

Objective: To analyze the prognosis and risk factors of lung metastasis of patients with adenoid cystic carcinoma(ACC) of head and neck. Methods: A retrospective study was conducted. The data of 157 patients with ACC of head and neck treated in Beijing Tongren Hospital, Capital Medical University from January 2014 to October 2020 were collected, including 72 males and 85 females, with onset age between 14 and 72 years old. According to whether lung metastasis occurred, the patients were divided into lung metastasis group (88 cases) and non-pulmonary metastasis group (69 cases). Kaplan-Meier method was used to calculate the overall survival rate and progression-free survival rate using SPSS 26.0 software. Log-rank test was used to evaluate statistically relevant clinicopathological factors. Cox proportional risk model was used in multivariate analysis for the factors affecting the lung metastasis-free survival using R Studio 1.2.5042. Results: The 3-year and 5-year overall survival rates were 91.5% and 85.2%, respectively. The 3-year and 5-year progression-free survival rates were 57.7% and 34.3%, respectively. Univariate analysis showed that primary site, histological grade, high-grade transformation, Ki-67, T stage, and lymph node status were the risk factors for lung metastasis (χ2=11.78, 10.41, 4.06, 4.71, 5.37, 16.20, respectively, all P<0.05). Multivariate analysis showed independent risk factors for lung metastasis, including submandibular gland and sublingual gland (HR=3.53, 95%CI: 1.19-10.46, P<0.05), T3-4 stage (HR=3.09, 95%CI: 1.54-6.23, P<0.05), and Grade Ⅱ-Ⅲ grade (HR=2.47, 95%CI: 1.26-4.86,P<0.05). Conclusion: Distant metastasis, mainly pulmonary metastasis, affects the long-term prognosis of patients with ACC significantly. Primary site, T stage and histopathological grade can be used as the predictors for the risk of lung metastasis.

[Clinical characteristics and prognosis of lymphoma-associated hemophagocytic syndrome].

Subjective To investigate clinical characteristics, treatment, and prognosis of lymphoma-associated hemophagocytic syndrome (LAHS) patients. Methods: The clinical data of patients diagnosed with LAHS from January 2010 to October 2021 in West China Hospital were retrospectively analyzed. Clinical characteristics, treatment, overall response rate (ORR), and overall survival (OS) were investigated. Univariate and multivariate analysis of potential factors were conducted. Results: Of all 94 patients included, 59 were male and 35 were female. The age at hemophagocytic lymphohistiocytosis (HLH) diagnosis was (40.5±17.3) years. Seventy-four cases were T/NK cell lymphoma; 15 were B cell lymphoma; 5 were Hodgkin lymphoma. The age at HLH diagnosis of T/NK cell LAHS patients was (37.9±16.2) years, while that of B cell LAHS patients was (55.9±14.0) years. T/NK cell LAHS patients were significantly younger than B cell LAHS patients (P<0.001). Baseline fibrinogen of T/NK cell LAHS patients was 1.34 (0.86, 2.44) g/L, while that of B cell LAHS patients was 2.20 (1.75, 4.25) g/L. T/NK cell LAHS patients showed significantly lower fibrinogen levels than B cell LAHS patients (P=0.008). Combined treatment of anti-HLH and anti-lymphoma treatment was conducted in 35 patients; anti-HLH treatment was conducted in 31 patients; anti-lymphoma treatment was conducted in 8 patients; glucocorticoid treatment was conducted in 7 patients. ORR was 49.4%, and the median OS was 61 days for overall patients. Patients who received anti-HLH treatment and turned to anti-lymphoma treatment early displayed the best ORR and OS, significantly higher than those of anti-HLH patients (69.0 vs 38.7%, P=0.019, and 192.0 vs 24.5 days, P=0.028, respectively), which were also insignificantly higher than those of anti-lymphoma patients. Extranodal NK/T-cell lymphoma or aggressive natural killer cell leukemia was the risk factor of LAHS prognosis (HR=0.113, 95%CI: 0.018-0.728, P=0.022). Conclusions: Prognosis of LAHS patients is poor. Anti-lymphoma treatment should be initiated as soon as HLH is rapidly controlled.

[Efficacy of relocation and expansion pharyngoplasty by suspension sutures in the treatment of OSAHS with soft palate oropharyngeal obstruction].

Objective: To explore the efficacy of relocation and expansion pharyngoplasty by suspension sutures in the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: Seventy-three patients(including 60 males and 13 females) with OSAHS admitted to the department of otorhinolaryngology of our hospital in recent two years were retrospectively analyzed. All the patients had velopharyngeal obstructionevaluated by electronic endoscopic Müller test and were divided into control group (34 cases) and observation group (39 cases). The patients in the control group were performed modified uvulopalatopharyngoplasty, while those in the observation group were performed relocation and expansion pharyngoplasty by suspension sutures.The scores of ESS, AHI and LSaO2 before and after treatment were collected and compared. Results: The total effective rate of the observation group was 94.87%, which was significantly higher than 79.41% of the control group. The AHI was lower and LSaO2 value was higher (χ2=-1. 896,-1. 968,P<0.05)in the observation group. The sleeping symptoms and quality of life of the two groups were significantly improved. The ESS score of the observation group was decreased more significantly than that of the control group after treatment, and the difference was statistically significant (χ2=-1.451,P<0.05). The incidence of foreign body sensation in pharynx of the observation group (89.74%) was higher than that of the control group (55.88%), and the postoperative bleeding and postoperative recurrence rate (0.00%, 2.56%) was lower than that of the control group (8.82%, 14.70%)with statistical significance (χ2=4.738,4.249,4.119,P<0.05).The incidence of transient nasopharyngeal reflux in both groups was low and statistically insignificant (χ2=0.629,P>0.05). Conclusions: Preoperative strict screening of indications plays an important role in the selection of palatopharyngeal surgery methods and curative effect. Relocation and expansion pharyngoplasty by suspension sutures can improve the clinical efficacy of OSAHS with better safety and less recurrence.

[Research of prognostic immunophenotypes in 163 patients of diffuse large B-cell lymphoma].

Objective: To screen and analyze the prognostic protein biomarkers of DLBCL, and to explore their value in the prognostic evaluation. Methods: 163 cases of confirmed DLBCLs from January 2011 to December 2016 were collected with their clinical, pathological and follow-up data, which were all from our hospital. The expression of protein markers were tested using immunohistochemical staining (IHC) . The immune phenotypes independent of the International Prognostic Index (IPI) that affect overall survival (OS) and progression-free survival (PFS) of DLBCL were explored by COX regression model, and the effect of their co-expression on the prognosis were also analyzed. Result: BCL6 negative (PFS: HR=1.652, 95%CI 1.030-2.649, P=0.037) , P53 positive (OS: HR=1.842, 95%CI 1.008-3.367, P=0.047) , and BCL2 strong positive expressions (S+) (OS: HR=2.102, 95%CI 1.249-3.537, P=0.005; PFS: HR=2.126, 95%CI 1.312-3.443, P=0.002) are adverse prognostic factors of DLBCL that are independent of IPI. BCL6(-) (PFS: HR=2.042, 95%CI 1.021-4.081, P=0.043) , P53(+) (OS: HR=3.069, 95%CI 1.244-7.569, P=0.015) and BCL2(S+) (OS: HR=2.433, 95%CI 1.165-5.082, P=0.018; PFS: HR=3.209, 95%CI 1.606-6.410, P=0.001) are adverse prognostic factors in the group of age≤60-year-old; in the group of IPI score 0-2, cases with BCL6(-) (OS: HR=2.467, 95%CI 1.322-4.604, P=0.005; PFS: HR=2.248, 95%CI 1.275-3.965, P=0.005) and BCL2(S+) (PFS: HR=2.045, 95%CI 1.119-3.735, P=0.020) have worse prognosis. The co-expression of BCL6(-) and BCL2(S+) has significant influence on prognosis of DLBCL (P=0.005 and P<0.001) , in which BCL6(+)/non-BCL2(S+) (n=86) has the best prognosis[3-year-OS (71.6±4.9) %, 3-year-PFS (67.0±5.1) %], and BCL6(-)/BCL2(S+) (n=10) has the worst prognosis[3-year-OS (20.0±12.6) %, 3-year-PFS (10.0±9.5) %]; the co-expression of BCL6(-) and P53(+) has no significant influence on prognosis (P=0.061 and P=0.089) , however, those cases with BCL6(+)/P53(-) (n=98) often get better prognosis[3-year-OS (70.6±4.7) %, 3-year-PFS (64.6±4.9) %] than others; the co-expression of P53(+) and BCL2(S+) has significant influence on prognosis of DLBCL (P<0.001 and P<0.001) , and P53(+)/BCL2(S+) (n=5) has the worst prognosis (3-year-OS and 3-year-PFS are both 0) ; BCL2(S+) cases get shorter OS and PFS, regardless of the expression of BCL6 and P53. Conclusion: The expression and co-expression of BCL6 negative, P53 positive and BCL2(S+) have certain value in the prognostic evaluation of DLBCL, especially in the group of age≤60-year-old and IPI score 0-2.

[CD38 dictates cardiac damage through mitochondrial apoptotic pathway under hypoxic-ischemic conditions].

Objective: To explore the mechanism of CD38-mediated cardiac damage under hypoxic-ischemic (H/I) conditions. Methods: Twenty CD38(-/-) male mice (8-week-old) and 20 wild-type (WT) male C57BL/6J mice (8-week-old) were randomly selected to construct the model of approximately 25% of the total body surface area (TBSA) burn injury. The cardiomyocytes (CMs) were separated from neonatal mice (1day) to construct the H/I injury model. Ad-CD38 adenovirus was transfected into CD38(-)/- primary CMs to callback CD38 expression. Animal experiments were grouped into WT-control group, CD38(-/-)-control group, WT-burn group, and CD38(-/-)-burn group (10 mice in each group). Primary CMs were divided into 6 groups: WT-normoxia group, CD38(-/-)-normoxia group, CD38(-/-)+Ad-CD38-normoxia group, WT-H/I group, CD38(-/-)-H/I group, CD38(-/-)+Ad-CD38-H/I group. The release of lactic dehydrogenase (LDH) from CMs and the cell viability were measured to estimate the level of myocardial injury. Ultrastructure of cardiomyocytes was examined by electron microscope. CD38 protein level and mitochondrial apoptosis-related proteins were detected by Western blot. Flow cytometry was used to detect mitochondrial reactive oxygen species (MitoSOX) of CMs under H/I condition. Cardiac function of mice was detected by ultrasonic apparatus. Results: (1) Animal experiments: The expression level of cardiac CD38 in WT-burn group was significantly higher than that in sham group (P<0.001). The heart function of CD38(-/-)-burn group was obviously better than WT-burn group [ejection fraction (EF)%: (84.70±2.31)% vs (76.10±2.96)%, shortening fraction (FS)%: (48.90±5.00)% vs (38.10±2.80)%] (both P<0.001). (2) Cell experiments: The expression level of cardiac CD38 in WT CMs under H/I condition was significantly higher than that in WT CMs under normoxia condition (P<0.05). The level of LDH, apoptotic cell and MitoSOX in CD38(-/-)-H/I group were fewer than WT-H/I group and CD38(-/-)+Ad-CD38(-)H/I group [(11.2±3.0)% vs (18.2±3.4)% and (17.6±4.0)%, (13.0±2.8)% vs (23.1±4.9)% and (23.3±6.0)%, (162±11)% vs (228±18)% and (220±18)%] (all P<0.001). The levels of cleaved-caspase3, Cytochrome-C in CD38(-/-)-H/I group were significantly lower than those in WT-H/I group and CD38(-/-)+Ad-CD38-H/I group (P<0.001). The cell viability in CD38(-/-)-H/I group was higher than that in WT-H/I group and CD38(-/-)+Ad-CD38-H/I group (0.355±0.043 vs 0.280±0.051 and 0.291±0.024) (all P<0.05). Electron microscopy results showed that structure of mitochondria in CD38(-/-)-H/I group was better than in WT-H/I group and CD38(-/-)+Ad-CD38-H/I group. Conclusion: Overexpression of CD38 contributes to cardiac damage by stimulating mitochondrial apoptotic pathway.

[Preoperative evaluation of sentinel lymph node biopsy using contrast-enhanced ultrasonography in early breast cancer patients and the involved disturbing factors].

Objective: To explore the preoperative evaluation of sentinel lymph node (SLN) biopsy using contrast-enhanced ultrasonography (CEUS) in early breast cancer patients and the involved disturbing factors. Methods: Eighty-three female early breast cancer patients who underwent concurrent surgery in the Affiliated Cancer Hospital of Zhengzhou University between January 2017 and May 2018 were enrolled. CEUS was used to seek SLN and determine lymph node metastasis after signature of preoperative informed consent. Rapid pathological examination was used to determine whether metastasis existed in SLN. The sensitivity, specificity, accuracy, the differences between CEUS and pathological results, and the involved disturbing factors were evaluated. Results: A total of 212 SLNs were detected by CEUS and SLN biopsy with an average of 2.6 SLNs detected per patient, including 39 SLNs with cancer metastasis (18.4%) and 173 SLNs without cancer metastasis (81.6%). Among the 83 patients, 29 patients were predicted SLN-positive preoperatively utilizing CEUS (including 21 cases with SLN pathological metastasis and 8 cases with non-metastasis), 54 patients were predicted SLN-negative (including 5 cases with SLN pathological metastasis and 49 cases with non-metastasis). The preoperative evaluation of SLN utilizing CEUS were performed with a sensitivity of 80.8% (21/26), specificity of 86.0% (49/57), positive predictive value of 72.4% (21/29), and negative predictive value of 90.7% (49/54), positive likelihood ratio of 5.75, negative likelihood ratio of 0.22, and the accuracy of 84.3% (70/83), respectively. The area under the ROC curve (AUC) was 0.834 (95% CI: 0.736-0.906). The primary tumor mean size of SLN-negative group predicted preoperatively utilizing CEUS was (1.78±0.14) cm, and that of the SLN positive group was (2.64±0.19) cm. The difference between the two groups was (0.86±0.24) cm with statistical significance (P=0.000 6). The SLN mean size of SLN-negative group (141 SLNs) was (1.41±0.05) cm and that of SLN-positive group (71 SLNs) was (1.69±0.07) cm. The difference between the two groups was (0.28±0.09) cm with statistical significance (P=0.002 8). Conclusions: Preoperative CEUS possesses the predictive value for SLN metastasis in early breast cancer. The predicted results may be influenced by the primary tumor size and the SLN size.

[The effect of the nasal packing material on nasal epithelial cells].

Objective:The aim of this study is to investigate the effect of polyethylene glycol acrylate hybrid hydrogel degradation substance on nasal mucociliary transport system. Method:In our experiment, the complex hydrogel were formed by the combination of different ratios of polyethyleneglycol diacrylate, chitosan and polyvinyl alcohol. The experiment was divided into four groups according to the international standard of medical devices. DMEM/F12∶BEGM culture medium was used for each packing material extraction, DMEM/F12∶BEGM culture medium was used as control. Human nasal uncinate tissue, gas liquid interface culture of human nasal mucociliary epithelium cells. The high frequency digital microscope video imaging system was used to detect the ciliary wiggle frequency. The baseline state (0 min) and 1 h,1 d, 2 d, 3 d of CBF were measured after dosing. Result:①In the experimental group and the control group, with the increase of the number of days, the ciliary beat frequency increased first and then slowed down. ②Compared with the other groups, Polyethylene glycol acrylate hybrid hydrogel group increase on CBF (P<0.05). There was no significant difference between the maximum increase and the maximum decrease in B, C and D groups (P>0.05). Therefore, it can be concluded that absorbable gelatin sponge material and absorbable chitosan material had no effect on nasal mucociliary activity. Conclusion:Polyethylene glycol diacrylate composite hydrogel material can increase the frequency of ciliary wounded nasal mucosa epithelial cells cultured in air-liquid interface in vitro, and enhanced the activity of nasal mucosa cilia. Therefore, it can meet the safety requirements of clinical application of the new material.

CircMTO1 inhibits cell proliferation and invasion by regulating Wnt/ß-catenin signaling pathway in colorectal cancer.

OBJECTIVE: Circular RNAs (circRNAs) play critical roles in disease incidence. However, the roles of circRNAs in colorectal cancer (CRC) progression remain largely unknown. We explored the expression of circMTO1 in CRC and elucidated the underlying molecular mechanisms. PATIENTS AND METHODS: Quantitative Real-time-PCR (qRT-PCR) was used to explore circMTO1 expression in CRC tissues and cell lines. The effect of circMTO1 on the biological function of CRC cells was analyzed by Cell Counting Kit-8 (CCK-8) assay, Edu assay, colony formation assay, wound-healing assay and transwell invasion assay. Gene expression and signaling pathway were detected by qRT-PCR and Western blot. RESULTS: QRT-PCR showed that circMTO1 expression was significantly decreased in CRC tissues and cell lines compared with adjacent non-tumor tissues and human normal colon epithelial cell line (FHC), respectively. Patients with low circMTO1 expression were correlated with advanced TNM stage, lymph node metastasis, and poor overall survival. Function assays demonstrated that circMTO1 inhibition promoted CRC cells proliferation and invasion ability in vitro. In addition, we showed that circMTO1 inhibition could promote CRC progression via activating Wnt/ß-catenin signaling pathway. CONCLUSIONS: We showed that circMTO1 could act as a tumor suppressor affecting the growth and invasion of CRC cells via regulating Wnt/ß-catenin signaling pathway, providing a novel potential biomarker and therapeutic target for CRC treatment.

LncRNALUADT1 is overexpressed in colorectal cancer and its expression level is related to clinicopathology.

OBJECTIVE: LncRNAs participate in the proliferation, apoptosis, and invasion of colorectal cancer. We aimed at investigating the uncovered effect of lncRNALUADT1 on colorectal cancer. PATIENTS AND METHODS: The relative expression level of lncRNALUADT1 in tumor specimen was tested by Real-time quantitative PCR. The association of lncRNALUADT1 with clinical pathological data was analyzed by univariate, multivariate Cox and Kaplan-Meier curve. RESULTS: LncRNALUADT1 expression was up-regulated in colorectal cancer, and correlated with tumor size, metastasis, and TNM staging. Both univariate analysis and multivariate test indicated that lncRNALUADT1 high expression, TNM staging, and lymph node metastasis were closely related. Moreover, high expression of lncRNALUADT1 suggested the poor overall survival of patients. CONCLUSIONS: LncRNA LUADT1 might contribute to the development of colorectal cancer.

Label-free rapid identification of tumor cells and blood cells with silver film SERS substrate.

The detection of circulating tumor cells (CTCs) from peripheral blood is considered as great significance for the diagnosis and prognosis of cancer patients. Raman spectroscopy is a highly sensitive optical detection technique that can provide fingerprint molecular identification information. In this paper, the silver film substrate surface-enhanced Raman scattering (SERS) was used to research several tumor cells, immortalized cells, clinical cancer cells isolated from cancer patient's tissue and blood cells. The results display that there is great difference for the nucleic acid characteristic peaks of those cells. The red blood cells have almost none nucleic acid characteristic peak and the SERS signals of white blood cells are only a slight increase. Except for immortalized cells and few tumor cells, the nucleic acid characteristic peaks of some tumor cells have huge enhancement. Nucleic acid characteristic peaks of clinical cancer cells also have greater enhancement. The discriminant model established by the intensity ratio of the nucleic acid characteristic peak 730 cm-1 to the substrate background peak 900 cm-1 shows that some tumor cells and clinical sample cells can be separated from white blood cells, but tumor cells with relatively low-DNA index cannot be differentiated from white blood cells. This study demonstrates that thin-film SERS technology can distinguish between blood cells and some types of tumor cells. This study opens up a new possible method for the detection of CTCs with label-free SERS spectra.

[The value of B7-H4 and carcinoembryonic antigen in diagnosing the benign and malignant pleural effusion].

Objective: To evaluate the value of combined detection of negative costimulatory molecule B7-H4 and carcinoembryonic antigen (CEA) in diagnosing malignant and benign pleural effusion. Methods: Ninety-seven pleural effusion specimen were collected, 55 of which were diagnosed as malignant pleural effusion and 42 were benign pleural effusion. Enzyme-linked immunosorbent assay(ELISA) was used to examine the concentration of B7-H4 and CEA in pleural effusion. Electro-chemiluminescence immunoassay was used to detect the CEA level in pleural effusion. Receiver operating characteristic (ROC) curve was established to analyze and evaluate the single or combined detection of B7-H4 and CEA in diagnosing malignant and benign pleural effusion. Results: The concentrations of B7-H4 and CEA in malignant pleural effusion (MPE) group were (60.08±35.04) ng/ml and (41.49±37.16) ng/ml, respectively, obviously higher than (27.26±9.55) ng/ml and (2.41±0.94) ng/ml of benign pleural effusion (BPE) group (both P<0.01). Area under curve (AUC) of B7-H4 was 0.884 in MPE groupand the diagnostic sensitivity and specificity were 81.8% and 90.5%, respectively, at the optimized cut off value of 37.25 ng/ml. Likewise, area under curve (AUC) of CEA was 0.954 and the sensitivity and specificity were 87.3% and 95.2%, respectively, at the cut off value of 4.18 ng/ml. When B7-H4 >37.25 ng/ml or CEA>4.18 ng/ml, the sensitivity of diagnosis as MPE was down-regulated to 90.9% and the specificity was elevated to 88.1%. When B7-H4 >37.25 ng/ml and CEA>4.18 ng/ml, the sensitivity of diagnosis as MPE was down-regulated to 78.2% and the specificity was elevated to 97.6%. The sensitivity and specificity of combined detection of B7-H4 and CEA to diagnose MPE were elevated to 90.9% and 97.6%, respectively. The level of B7-H4 in MPE and BPE were both positively correlated with CEA (r=0.670, P=0.001 in MPE and r=0.002, P=0.001 in BEP). Conclusions: B7-H4 is a potential tumor marker in diagnosing the benign and malignant pleural effusion. Although the diagnostic value of B7-H4 may not precede to CEA, the combined detection of B7-H4 and CEA can improve the diagnostic sensitivity and specificity of MPE.

[The breast cancer diagnosis accuracy of the digital breast tomosynthesis technique].

Objective: To explore the Digital breast tomosynthesis technique (DBT) in breast cancer diagnosis accuracy. Methods: Choose 263 cases of patients with breast lesions, using DBT combined FFDM (Full field digital mammography) independent FFDM, evaluate the diagnostic accuracy of breast cancer. Results: The ROC curve area (AUC) of two kinds of breast cancer diagnosis methods (DBT combined FFDM and independent FFDM) were 0.954±0.014 and 0.907±0.019, with significant difference (P=0.000 3). In premenopausal patients and breast density ACR3-4 cases, DBT combined FFDM diagnosis accuracy is higher than FFDM alone group, with significant difference (P<0.05). Conclusion: DBT combined FFDM compared with independent FFDM, in a certain extent, improves the accuracy of the diagnosis of breast cancer.

[Intertumoral heterogeneity of molecular phenotype and analysis of prognosis in multifocal and multicentric breast cancer].

Objective: This study was designed to investigate the prognostic implications of the intertumoral heterogeneity of molecular phenotype in multifocal and multicentric breast cancer (MMBC). Methods: The clinical and follow-up data of 146 patients with MMBC from Jan.2009 to Dec. 2009 treated in Tumor Hospital Affiliated to Zhengzhou University were retrospectively analyzed. We used Kaplan-Meier curves to compare the survivals of patients who had tumors with molecular phenotypic heterogeneity and patients who had multifocal homogeneous tumors in molecular phenotype, and the survivals of patients who had heterogeneous tumor type and grade and who had homogeneous tumor type and grade.The corresponding hazard ratio was calculated by Cox proportional-hazards regression. Results: Intertumoral heterogeneity in histological type and grade of multiple breast cancer was detected in 16 of 146 patients (11.0%) and in 10 of 146 patients (6.8%), respectively. Interfocal heterogeneous molecular phenotype of multiple breast cancer was detected in 24 of 146 patients (16.4%). There was no significant difference in 5-year disease-free survival in multifocal cancer patients who had heterogeneous histological type and grade and who had homogeneous type and grade tumors (75.0% vs. 77.3%, P=0.808). Multifocal cancers patients who had heterogeneous tumorsin molecular phenotype compared with those with homogeneous tumors in molecular phenotype had worse 5-year disease-specific survival (78.7% vs. 58.3%, P=0.037), and had a greater risk of recurrence (HR=2.130, 95%CI=1.027-4.420; P=0.042). Phenotyping the additional cancer foci influenced the therapeutic decision in up to 16 patients(11.0%). Conclusions: Multifocal breast cancer patients who had heterogeneous tumors in molecular phenotype have a statistically significantly shorter disease-free survival. Phenotyping the additional cancer foci and managing with proper therapeutic decision may reduce the risk of recurrence or metastasis, and improve the outcomes of the patients.

The Co-regulatory Role of 5-Lipoxygenase and Cyclooxygenase-2 in the Carcinogenesis and their Promotion by Cigarette Smoking in Colons.

The arachidonic acid metabolizing enzymes, cyclooxygenase-2 (COX-2) and 5- lipoxygenase (5-LOX), are both highly expressed during the carcinogenesis in colons. Cigarette smoking promotes these carcinogenic processes at the early stage during adenoma formation. In this article, the involvement of COX-2 and 5-LOX, alongside with the dual COX/5-LOX inhibitors in colorectal cancer development is introduced. The co-regulation of 5-LOX and COX-2 in colon cancer growth and its relationship with cigarette smoke and hyaluronic acid-CD44v6 is also described. It is envisaged that dual inhibition of 5-LOX/COX could be the most promising therapeutic option for the treatment of colorectal cancer in humans.

Cigarette smoking and gastrointestinal diseases: the causal relationship and underlying molecular mechanisms (review).

Cigarette smoking is an important risk factor for gastrointestinal (GI) disorders, including peptic ulcers, inflammatory bowel diseases, such as Crohn's disease and cancer. In this review, the relationship between smoking and GI disorders and the underlying mechanisms are discussed. It has been demonstrated that cigarette smoking is positively associated with the pathogenesis of peptic ulcers and the delay of ulcer healing. Mechanistic studies have shown that cigarette smoke and its active ingredients can cause mucosal cell death, inhibit cell renewal, decrease blood flow in the GI mucosa and interfere with the mucosal immune system. Cigarette smoking is also an independent risk factor for various types of cancer of the GI tract. In this review, we also summarize the mechanisms through which cigarette smoking induces tumorigenesis and promotes the development of cancer in various sections of the GI tract. These mechanisms include the activation of nicotinic acetylcholine receptors, the formation of DNA adducts, the stimulation of tumor angiogenesis and the modulation of immune responses in the GI mucosa. A full understanding of these pathogenic mechanisms may help us to develop more effective therapies for GI disorders in the future.