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ABSTRACT: Chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic. The combination of cisplatin with other agents has been recognized as a promising strategy to overcome cisplatin resistance. Previous studies have shown that wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid isolated from the root of the medicinal herb Scutellaria baicalensis Georgi, sensitizes cancer cells to chemotheraputics such as etoposide, adriamycin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TNF. However, the effect of wogonin on cisplatin-induced cytotoxicity has not been previously reported. In this study, the non-small cell lung cancer cell line A549 and the cervical cancer cell line HeLa were treated with wogonin or cisplatin individually or in combination. It was found for the first time that wogonin is able to sensitize cisplatin-induced apoptosis in both A549 cells and HeLa cells as indicated by the potentiation of activation of caspase-3, and cleavage of the caspase-3 substrate PARP in wogonin and cisplatin co-treated cells. Importantly, wogonin robustly induced H2O2 accumulation in these cells, which substantially contributes to the sensitization of cisplatin cytotoxicity by wogonin, as two reactive oxygen species scavengers, butylated hydroxyanisole (BHA) and N-acetyl-L-cysteine (NAC), significantly suppressed the potentiated cytotoxicity caused by wogonin and cisplatin co-treatment. The results from this study provide important new evidence supporting the potential use of wogonin as a cisplatin sensitizer for cancer therapy.
Oncology Reports 05/2012; 28(2):601-5. · 1.84 Impact Factor
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Hong Sun,
Ying-Jia Zhong, Xue-Lian Zheng,
Qiong Wang,
Lan Yang,
Fang Shi,
Jia-Qi Yan,
Fan He,
Lin-Chuan Liao,
Yong Lin,
Lin Zhang,
Xia Wang
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ABSTRACT: Activation of CD40, a member of the tumor necrosis factor receptor (TNF-R) family, results in growth inhibition or apoptosis in some tumor cells, making CD40 a potential antitumor therapeutic target. Although it is known that CD40 is able to induce tumor necrosis factor-alpha (TNF-α) secretion and potentiate cisplatin's anticancer activity, whether TNF-α induction is involved in sensitizing cisplatin by CD40 has not been addressed. In this report, we provide evidence substantiating an important role of autocrine TNF-α in potentiation of cisplatin-induced apoptosis by recombinant soluble CD40 ligand (rsCD40L) in different human cancer cell lines. Activation of CD40 by rsCD40L induces two phases of autocrine TNF-α: the rapid early phase involving p38 MAP kinase and the robust and persistent late phase through enhanced tnf-α gene transcription. Blocking TNF-α with either a specific TNFR1 siRNA or a neutralizing anti-TNF-α antibody dramatically attenuated the potentiation effect of rsCD40L on cisplatin-induced cancer cell death. These results reveal an important role of TNF-α induction in CD40's chemosensitization activity and suggest that modulating TNF-α autocrine from cancer cells is an effective option for increasing the anticancer value of chemotherapeutics such as cisplatin.
Cancer Science 02/2012; 103(2):197-202. · 3.33 Impact Factor
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Ying-jia Zhong,
Fang Shi, Xue-lian Zheng,
Qiong Wang,
Lan Yang,
Hong Sun,
Fan He,
Lin Zhang,
Yong Lin,
Yong Qin,
Lin-chuan Liao,
Xia Wang
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ABSTRACT: To investigate the anticancer effect of crocetin, a major ingredient in saffron, and its underlying mechanisms.
Cervical cancer cell line HeLa, non-small cell lung cancer cell line A549 and ovarian cancer cell line SKOV3 were treated with crocetin alone or in combination with vincristine. Cell proliferation was examined using MTT assay. Cell cycle distribution and sub-G(1) fraction were analyzed using flow cytometric analysis after propidium iodide staining. Apoptosis was detected using the Annexin V-FITC Apoptosis Detection Kit with flow cytometry. Cell death was measured based on the release of lactate dehydrogenase (LDH). The expression levels of p53 and p21(WAF1/Cip1) as well as caspase activation were examined using Western blot analysis.
Treatment of the 3 types of cancer cells with crocetin (60-240 μmol/L) for 48 h significantly inhibited their proliferation in a concentration-dependent manner. Crocetin (240 μmol/L) significantly induced cell cycle arrest through p53-dependent and -independent mechanisms accompanied with p21(WAF1/Cip1) induction. Crocetin (120-240 μmol/L) caused cytotoxicity in the 3 types of cancer cells by enhancing apoptosis in a time-dependent manner. In the 3 types of cancer cells, crocetin (60 μmol/L) significantly enhanced the cytotoxicity induced by vincristine (1 μmol/L). Furthermore, this synergistic effect was also detected in the vincristine-resistant breast cancer cell line MCF-7/VCR.
Ccrocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug or as a chemosensitizer for vincristine.
Acta Pharmacologica Sinica 12/2011; 32(12):1529-36. · 1.95 Impact Factor
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ABSTRACT: To investigate the effect of heat shock protein 90 (HSP90) inhibitor 17-dimethylaminoethylaminogeldanamycin (17DMAG) on tumor necrosis factor alpha (TNFalpha) mediated apopotosis in cancer cells and the underlying molecular mechanisms.
Cell death treated with different concentration of 17DMAG and TNFalpha was detected based on the release of lactate dehydrogenase (LDH) using a cytotoxicity detection kit. For morphological study of cell death, cells were stained with 50 microg/mL of acridine orange and 50 microg/mL of ethidium bromide and observed and photographed under a fluorescence microscope. Activation of apoptosis and NF-kappaB pathway were evaluated on the change of caspase-8, caspase-3, poly (ADP-ribose) polymerase (PARP), receptor-interaction protein (RIP), IkappaB kinase beta (IKKbeta) and inhibitor of IkappaB (IkappaBalpha) by Western blot.
17DMAG sensitized cervical cancer cells HeLa and ovarian cancer cells SKOV3 to TNFalpha-induced cell death in a dose-dependent manner, which was accompanied with degradation of RIP and Ikappakappabeta, and consequent blockage of TNFalpha-induced NFkappaB activation. 17DMAG and TNFalpha cotreated cells showed typical apoptotic morphologies and enhancing of activation of caspases.
17DMAG sensitizes cancer cells to TNFalpha-mediated apoptosis through blockage of TNF-induced NF-kappaB activation, and disabling this survival signal with 17DMAG followed by TNF treatment could be an effective new therapeutic strategy for improving the anti-cancer value of TNFalpha.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 05/2011; 42(3):303-7.
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Lan Yang, Xue L Zheng,
Hong Sun,
Ying J Zhong,
Qiong Wang,
Hai N He,
Xun W Shi,
Bing Zhou,
Jin K Li,
Yong Lin,
Lin Zhang,
Xia Wang
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ABSTRACT: Tremendous effort has been made to improve the anticancer value of tumor necrosis factor (TNF). In this study, we show that wogonin, a flavonoid isolated from Huang-Qin (Scutellaria baicalensis), synergistically sensitizes cancer cells derived from the cervix, ovary and lung to TNF-induced apoptosis, which was associated with inhibition of catalase activity and an increase of cellular hydrogen peroxide (H(2)O(2)). Wogonin-induced reactive oxygen species block TNF-induced NF-κB activation through inhibiting phosphorylation on the NF-κB p65 subunit and consequently the DNA binding of NF-κB. In addition, wogonin suppressed the expression of the antiapoptotic factor c-FLIP, which is accompanied with potentiation of TNF-induced caspase 8 activation that initiates apoptosis. Importantly, wogonin did not sensitize normal bronchial epithelial cells to TNF-induced cell death, which was associated with the defect in induction of H(2)O(2). Thus, wogonin specifically sensitizes cancer cells to TNF-induced cytotoxicity through H(2)O(2)-mediated NF-κB suppression and apoptosis activation. Our data provide important insights into the molecular mechanism underlying wogonin's anticancer activity, and suggest this common flavonoid could be used as a TNF adjuvant for cancer therapy.
Cancer Science 01/2011; 102(4):870-6. · 3.33 Impact Factor
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Hai-Ning He,
Xia Wang, Xue-Lian Zheng,
Hong Sun,
Xun-Wei Shi,
Ying-Jia Zhong,
Bo Huang,
Lan Yang,
Jin-Ke Li,
Lin-Chuan Liao,
Lin Zhang,
Li-Na Hu,
Yong Lin
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ABSTRACT: Nuclear factor-kappaB (NF-kappaB) and Akt are two major cell survival pathways that are often constitutively activated and can be further stimulated by chemotherpeutics in cancer cells. Although individually targeting the NF-kappaB or Akt has been reported to sensitize caner therapy, the effectiveness of concurrent blocking these two pathways for chemosensitizing of cancer cells to genotoxic therapeutics has not been investigated. In the present study, we investigate the activation of the NF-kappaB and Akt pathways by two frontline anticancer drugs cisplatin and etopside in a variety of cancer cell lines. The effects of blocking these two survival pathways individually or concurrently on cisplatin- or etopside-induced cytotoxicity were detected. The results show that cisplatin and etopside activate both NF-kappaB and Akt in cancer cells. Blockade of either of these pathways with chemical inhibitors or siRNA moderately sensitized cancer cells to cisplatin- or etopside-induced cytotoxicity. Strikingly, much more effective potentiation of cytotoxicity to these anticancer drugs was achieved when NF-kappaB and Akt were concurrently blocked. These data suggest that NF-kappaB and Akt cooperatively attenuate therapeutic-induced cytotoxicity and concurrently blocking these pathways is an effective strategy for improving the anticancer efficacy of therapeutics.
Cancer letters 03/2010; 295(1):38-43. · 4.86 Impact Factor
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ABSTRACT: Saikosaponin-a and -d, two naturally occurring compounds derived from Bupleurum radix, have been shown to exert anti-cancer activity in several cancer cell lines. However, the effect of combination of saikosaponins with chemotherapeutic drugs has never been addressed. Thus, we investigated whether these two saikosaponins have chemosensitization effect on cisplatin-induced cancer cell cytotoxicity.
Two cervical cancer cell lines, HeLa and Siha, an ovarian cancer cell line, SKOV3, and a non-small cell lung cancer cell line, A549, were treated with saikosaponins or cisplatin individually or in combination. Cell death was quantitatively detected by the release of lactate dehydrogenase (LDH) using a cytotoxicity detection kit. Cellular ROS was analyzed by flow cytometry. Apoptosis was evaluated by AO/EB staining, flow cytometry after Anexin V and PI staining, and Western blot for caspase activation. ROS scavengers and caspase inhibitor were used to determine the roles of ROS and apoptosis in the effects of saikosaponins on cisplatin-induced cell death.
Both saikosaponin-a and -d sensitized cancer cells to cisplatin-induced cell death in a dose-dependent manner, which was accompanied with induction of reactive oxygen species (ROS) accumulation. The dead cells showed typical apoptotic morphologies. Both early apoptotic and late apoptotic cells detected by flow cytometry were increased in saikosaponins and cisplatin cotreated cells, accompanied by activation of the caspase pathway. The pan-caspase inhibitor z-VAD and ROS scavengers butylated hydroxyanisole (BHA) and N-acetyl-L-cysteine (NAC) dramatically suppressed the potentiated cytotoxicity achieved by combination of saikosaponin-a or -d and cisplatin.
These results suggest that saikosaponins sensitize cancer cells to cisplatin through ROS-mediated apoptosis, and the combination of saikosaponins with cisplatin could be an effective therapeutic strategy.
Journal of Experimental & Clinical Cancer Research 01/2010; 29:159. · 2.15 Impact Factor
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Ke-Ling Chen, Xue-Lian Zheng,
Yuan Li,
Lie Yang,
Zong-Guang Zhou,
Xiang-Yu Zhou,
Bin Zhou,
Rong Wang,
Jing-Jing Jiang,
Li-Hui Chen,
Lan Zhan
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ABSTRACT: Pancreatic duct epithelial cells (PDEC) are involved in most common pancreatic diseases. Primary cultivation of PDEC is a prerequisite for in vitro studies, in which in vivo situations can be simulated and molecular mechanisms investigated better than in cultured cell lines. However, some problems still exist regarding rat PDEC primary cultivation. In this study, an improved primary culture system of rat PDEC is presented. Some modifications, especially regarding specimen chosen, digestive control and epithelium purification, were made to simplify the procedure, increase cell yield, and improve epithelium purification. Cultures were identified as PDEC by morphological characteristics, reverse transcription-polymerase chain reaction and immunocytochemistry staining with cytokeratin 19. In addition, growth characteristics of rat PDEC are described in detail. This improved technique, which is more efficient and cost-effective, will be useful for in vitro pancreatic studies.
Cytotechnology 08/2009; · 1.21 Impact Factor
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ABSTRACT: To investigate the expression of phosphatase of regeneration liver-3(PRL-3) protein and its relationship with tumor invasion and metastasis in human colorectal carcinoma,and elucidate prognostic value.
Immunohistochemistry method was applied to detect the PRL-3 expression in the primary tumor specimens and paired paratumor normal tissues from 46 colorectal carcinoma patients, the adenoma tissues from 6 patients with colorectal adenoma, all the metastatic lymph nodes from 29 cases and the metastatic liver lesions from 6 cases. The relationship between PRL-3 expression and clinicopathologic parameters was analyzed and a survival curve was achieved according to Kaplan-Meier method.
No or weak PRL-3 protein expression was detected in normal colorectal mucosa and colorectal adenoma. In colorectal carcinoma tissues, PRL-3 expression was confirmed in 26 of 46 cases (56.5%) of primary colorectal carcinomas (with lymph node metastasis 63.0%, without lymph node metastasis 37.0%, P=0.001), 26 of 29 (89.7%) lymph node metastases, and 5 of 6 liver metastases. The expression of PRL-3 was assembled in the cytoplasm of carcinoma cells and more intensively on the cell membrane.Analysis of the relationship between PRL-3 expression and the clinicopathologic features showed that PRL-3 expression was closely associated with tumor stage (P=0.019), lymph node metastasis (P=0.026), but no relationship with age, sex, tumor size, degree of differentiation was founded (P<0.05). The mean follow-up time was 41.4 months and results showed that patients with positive expression of PRL-3 had a significantly poorer prognosis than those with negative PRL-3 expression group(P=0.032).
PRL-3 protein plays a novel role in tumor progression and metastasis of colorectal carcinoma. PRL-3 can be expected to be a potential predictive biomarker for identifying the prognosis in colorectal carcinoma patients.
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 10/2008; 11(5):487-91.
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ABSTRACT: To research the reliable method for the isolation and culture of Kupffer cell in BALB/c mouse by mixed enzyme.
Kupffer cells were isolated from liver by in situ perfusion and digestion with 0.1% IV collagenase, 0.2% pronase and 0.01% Dnase I, and by percoll density gradient centrifugation. Kupffer cells were identified by fluorescence microscope, immunohistochemistry and cell endocytosis effect.
Kupffer cells were isolated successfully with high purity, the yield of (2-3) 10(6)/per mouse liver and the identification that 0.4% trypan blue indicated that the cells survival rate and purity were more than 96% and more than 92% respectively. The shape of Kupffer cell appeared to be multiplicity, irregularity, polygon and multiangular. Kupffer cells showed lysozyme positive by immunohistochemistry staining. And particles of India ink were found in cytoplasm.
Here described technique for isolation and culture of Kupffer cells is simple and reliable, and can be used for preparing Kupffer cells with high yield, activity and purity.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 03/2008; 39(2):298-301.
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ABSTRACT: We sought to study Toll-like receptor 4 (TLR4) expression on peripheral blood mononuclear cells (PBMCs) during the early stage of human acute pancreatitis (AP). Thirty consecutive patients with acute pancreatitis admitted within 24 hr of onset of abdominal pain were enrolled prospectively in this study. Blood samples were taken by venipuncture at admission and on the third and seventh days after admission. PBMCs were isolated, and TLR4 and CD14 expression on PBMCs was detected by flow cytometer. Serum tumor necrosis factor (TNF)-alpha, interleukin, and lipase were detected simultaneously. Relations among these parameters were analysis. In mild AP, TLR4 expression increased on the first day of admission and then continued to decline for several days. On the seventh day, TLR4 expression was almost normal compared with that of the normal control. The alteration of serum TNF-alpha was coincidence with TLR4. We conclude that mononuclear-macrophages might be ignited through TLR4 (the gatekeeper of the innate immune system) and lead to production of TNF-alpha.
Digestive Diseases and Sciences 09/2007; 52(8):1973-8. · 2.12 Impact Factor
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Wen-Jian Meng,
Ling Wang,
Chao Tian,
Yong-Yang Yu,
Bing Zhou,
Jun Gu,
Qing-Jie Xia,
Xiao-Feng Sun,
Yuan Li,
Rong Wang, Xue-Lian Zheng,
Zong-Guang Zhou
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ABSTRACT: To establish the role of human T Cell Factor-4 (hTCF-4) gene exons 3-9 mutation status in association with sporadic rectal cancer with microsatellite instability (MSI).
Microsatellite markers were genotyped in 93 sporadic rectal cancer patients. Eleven cases were found to be high-frequency MSI (MSI-H). Sequence analysis of the coding region of the exons 3-9 of hTCF-4 gene was carried out for the 11 MSI-H cases and 10 controls (5 microsatellite stability (MSS) cases and 5 cases with normal mucosa). The sequencing and MSI identification were used.
Several novel mutations and variants were revealed. In exon 4, one is a 4-position continuous alteration which caused amino acid change from Q131T and S132I (391insA, 392 G > A, 393 A > G and 395delC) and another nucleotide deletion (395delC) is present in MSI-H cases (5/10 and 4/10, respectively) but completely absent in the controls.
Novel mutations in exon 4 of hTCF-4 gene were revealed in this study, which might be of importance in the pathogenesis of sporadic rectal cancer patients with MSI-H.
World Journal of Gastroenterology 07/2007; 13(27):3747-51. · 2.47 Impact Factor
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Wen-Jian Meng,
Xiao-Feng Sun,
Chao Tian,
Ling Wang,
Yong-Yang Yu,
Bing Zhou,
Jun Gu,
Qing-Jie Xia,
Yuan Li,
Rong Wang, Xue-Lian Zheng,
Zong-Guang Zhou
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ABSTRACT: Tumors with high-frequency microsatellite instability (MSI-H) have unique biological behavior and the predictive role of microsatellite instability (MSI) status on survival of colorectal cancer is still debated. The prognostic significance of MSI status in sporadic stage II and III rectal cancer patients needs to be more precisely defined. So we investigated the relationship between MSI status and clinicopathological features and prognosis in these patients.
DNAs from fresh-frozen paired samples of tumors and corresponding normal tissue from 128 stage II and III rectal cancer patients were analyzed for MSI by PCR amplification using markers recommended by a National Cancer Institute workshop on MSI. To assess prognostic significance, Cox proportional hazards modeling was used.
Twelve (9.3%) tumors in our study were MSI-H, 28 (21.9%) were low-frequency MSI (MSI-L) and 88 (68.8%) were microsatellite stable (MSS). Most of the MSI-H tumors compared with MSI-L and MSS tumors were found in female patients (p = 0.031), had mucinous histology (p = 0.023), high grade of differentiation (p = 0.002) and high level of preoperative serum carcinoembryonic antigen (p = 0.005). Rectal cancer patients with MSI-H did not show a better clinical outcome than those with MSI-L/MSS, neither in all cases (p = 0.986) nor in stage II and stage III disease analyzed separately (p = 0.705 and p = 0.664, respectively).
Data provided here demonstrated there was high incidence of MSI-H and MSI was not a prognostic factor in sporadic stage II and III rectal cancers from the Chinese Han population included in this study. Tumor stage is more suitable than MSI status for prediction of individual survival in sporadic stage II and III rectal cancer patients.
Oncology 02/2007; 72(1-2):82-8. · 2.27 Impact Factor
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ABSTRACT: There is increasing evidence to indicate that MMP-7 plays a more important role in tumor progression than other MMPs. The aim of this study was to detect MMP-7 expression in human rectal cancer and normal rectal tissue and to determine whether it is correlated with invasion and metastasis of human rectal cancer.
Eighty-six paired samples of rectal cancer and distant normal rectal tissue obtained from 100 inpatients were allocated into two groups (cancer group and control group). MMP-7 mRNA was detected by relative quantitative real-time RT-PCR and MMP-7 protein was examined by immunohistochemical staining and computerized image analysis.
MMP-7 mRNA expression in cancer group was higher than that in control group (P = 0.006), the expression ratios of 31 samples (37.35%) were <1 and 52 (62.65%) were >1. The mRNA expression level was correlated with Dukes Staging, histological differentiation grade and CEA level. The MMP-7 protein expression was in accordance with mRNA expression level. The positive degree of immunohistochemical staining in cancer group (1.82 +/- 0.03) was different from that in control group (1.17 +/- 0.13, P = 0.002). Moreover, in cancer group the positive staining degree in high-level mRNA cancers (2.04 +/- 0.18, n = 52) was higher than that in low-level mRNA ones (1.58 +/- 0.23, n = 31, P = 0.008).
Our results suggest that MMP-7 plays an important role in the progression of human rectal cancer. MMP-7 may be selected as a clinical diagnosis and prognosis index in rectal cancer.
Japanese Journal of Clinical Oncology 12/2005; 35(12):739-44. · 1.78 Impact Factor
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ABSTRACT: To investigate the expression of phosphatase of regenerating liver-3 (PRL- 3) mRNA and evaluate its relationship with tumor invasion and metastasis in human colorectal carcinoma.
The expression level of PRL-3 mRNA was examined semi-quantitatively in surgically resected tumor specimens, paired paratumor normal tissues from 46 CRC patients, metastatic lymph nodes and liver metastases from 18 cases with metastasis,adenoma tissues from 6 patients with colorectal adenoma (CRA). In addition,the mutation of PRL-3 gene was examined by PCR-SSCP.
The PRL-3 mRNA level was increased in primary CRC tissues as compared with paired paratumor normal tissues (1.6+/- 0.7 vs. 0.4+/- 0.1, P< 0.01), while no significant difference of its expression was found between CRA tissues and their adjacent normal mucosae (P> 0.05). However,the PRL-3 mRNA levels of liver metastases (2.1+/- 0.8) in 12 cases and metastatic lymph nodes (3.3+/- 1.0) in 6 cases were significantly higher compared with the matched primary lesions, normal tissues and negative-lymph nodes (P< 0.01). There was significant relation of the expression of PRL-3 mRNA with the clinicopathological features including Dukes stage, invasion depth and metastasis (P< 0.05), but no relation with sex,tumor size,degree of differentiation was found (P> 0.05). Abnormal electrolysis band was found in 1 of 6 cases with liver metastasis by PCR-SSCP analysis.
PRL-3 gene plays an important role in tumor invasion and metastasis and may associated with carcinogenesis and development of CRC. There might exist some unknown mechanisms of overexpression and mutation of PRL-3 gene in CRC.
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 05/2005; 8(3):237-40.
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ABSTRACT: Local recurrence after curative surgical resection for rectal cancer remains a major problem. Several studies have shown that incomplete removal of cancer deposits in the distal mesorectum contributes a great share to this dismal result. Clinicopathologic examination of distal mesorectum in lower rectal cancer was performed in the present study to assess the incidence and extent of distal mesorectal spread and to determine an optimal distal resection margin in sphincter-saving procedure.
We prospectively examined sepecimens from 45 patients with lower rectal cancer who underwent curative surgery. Large-mount sections were performed to microscopically observe the distal mesorectal spread and to measure the extent of distal spread. Tissue shrinkage ratio was also considered. Patients with involvement in the distal mesorectum were compared with those without involvement with regard to clinicopathologic features.
Mesorectal cancer spread was observed in 21 patients (46.7%), 8 of them (17.8%) had distal mesorectal spread. Overall, distal intramural and/or mesorectal spreads were observed in 10 patients (22.2%) and the maximum extent of distal spread in situ was 12 mm and 36 mm respectively. Eight patients with distal mesorectal spread showed a significantly higher rate of lymph node metastasis compared with the other 37 patients without distal mesorectal spread (P = 0.043).
Distal mesorectal spread invariably occurs in advanced rectal cancer and has a significant relationship with lymph node metastasis. Distal resection margin of 1.5 cm for the rectal wall and 4 cm for the distal mesorectum is proper to those patients who are arranged to receive operation with a curative sphincter-saving procedure for lower rectal cancer.
World Journal of Gastroenterology 02/2005; 11(3):319-22. · 2.47 Impact Factor
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ABSTRACT: To examine the effects of analogs of pituitary adenylate cyclase activating polypeptide (PACAP)--PACAP6-27 (10, 100 microg/kg) and (4-Cl-D-Phe6, Leu17)VIP (10, 100 microg/kg) on the pancreata of normal rats and on the development of experimental acute pancreatitis.
Male Wistar rats were allocated into normal control groups, experimental acute pancreatitis groups and PACAP analog intervention groups. Acute pancreatitis was induced with s.c. cerulein and intraductal sodium taurocholate; PACAP analogs were infused intravenously immediately after pancreatitis induction. Pancreatic morphology was observed at 4 h, and serum amylase, pancreatic water content and PACAP contents were measured.
It was found that PACAP6-27 induced pancreatic edema, inflammatory cell infiltration, and elevation of serum amylase [(1464.33 +/- 265.6)-(1692.17 +/- 312.18)] IU/L vs (520.8 +/- 163.27) IU/L of control, P < 0.05); that PACAP6-27 aggravated vacuolization of pancreatic acinar cells in cerulein-induced pancreatitis with hemorrhage and fatty and parenchymal necrosis; and that the pathological changes of cerulein plus 100 microg/kg PACAP group were similar to those of sodium taurocholate-induced pancreatitis. Pancreatic hemorrhage, vacuolization of acinar cells and parenchymal necrosis in sodium taurocholate-induced pancreatitis were worsened by PACAP6-27. (4-Cl-D-Phe6, Leu17)VIP had similar effects. ELISA showed that pancreatic and duodenal levels of PACAP were increased in cerulein- and sodium taurocholate-induced pancreatitis.
PACAP6-27 and (4-Cl-D-Phe6, Leu17)VIP could induce mild pancreatitis and aggravate experimental acute pancreatitis. PACAP probably plays a role in the pathogenesis of acute pancreatitis.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 01/2005; 36(1):64-8.
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ABSTRACT: To assess the microscopic spread of low rectal cancer in mesorectum regions to provide pathological evidence for the necessity of total mesorectal excision (TME).
A total of 62 patients with low rectal cancer underwent low anterior resection and TME, surgical specimens were sliced transversely on the serial embedded blocks at 2.5 mm interval, and stained with hematoxylin and eosin (HE). The mesorectum on whole-mount sections was divided into three regions: outer region of mesorectum (ORM), middle region of mesorectum (MRM) and inner region of mesorectum (IRM). Microscopic metastatic foci were investigated microscopically on the sections for the metastatic mesorectal regions, frequency, types, involvement of lymphatic vessels and correlation with the original rectal cancer.
Microscopic spread of the tumor in mesorectum and ORM was observed in 38.7% (24/62) and 25.8% (16/62) of the patients, respectively. Circumferential resection margin (CRM) with involvement of microscopic metastatic foci occurred in 6.5% (4/62) of the patients, and distal mesorectum (DMR) involved was 6.5% (4/62) with the spread extent within 3 cm of low board of the main lesions. Most (20/24) of the patients with microscopic metastasis in mesorectum were in Dukes C stage.
Results of the present study support that complete excision of the mesorectum without destruction of the ORM is essential for surgical management of low rectal cancer, an optimal DMR clearance resection margin should be no less than 4 cm, further pathologic assessment of the regions in extramesorectum in the pelvis is needed.
World Journal of Gastroenterology 11/2004; 10(20):2949-53. · 2.47 Impact Factor
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ABSTRACT: To investigate the role of inducible cyclooxygenase (COX-2) mRNA expression in local microvessels in rats with acute interstitial pancreatitis (AIP) induced by caerulein injection.
The reverse transcription polymerase chain reaction (RT-PCR) was used to detect COX-2 gene expression in pancreatic tissue. Parameters of acute pancreatitis, such as serum amylase (AMS) and plasma myeloperoxidase (MPO) activities, were assayed using spectrophotometry. Intravital fluorescence microscopy with fluorescein isothiocyanate-labelled erythrocytes was used to study the pancreatic microvessels of rats with AIP and normal control rats.
Highly significant increases in COX-2 expression and AMS and MPO activity were seen in rats with AIP compared with controls. After caerulein injection, pancreatic capillary blood flow was decreased (4 hours, p > 0.05; 8 hours, p < 0.001), functional capillary density was reduced (4 hours, p > 0.05; 8 hours, p < 0.001), and there was irregular and intermittent capillary perfusion at 8 hours. There was also a positive correlation between the level of COX-2 expression and MPO activity (plasma, r = 0.5449, p < 0.05; tissue, r = 0.5698, p < 0.05).
The correlations between increased COX-2 expression and decreased capillary perfusion and blood flow and increased oedema following AIP may show that COX-2 expression can induce neutrophil sequestration to the pancreas, which may be one of the cascading inflammatory factors in the development of AIP.
Asian Journal of Surgery 04/2004; 27(2):93-8. · 0.57 Impact Factor
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ABSTRACT: To investigate the regional spread of microscopic tumor nodules in the mesorectum of patients with low rectal cancer, and to provide further pathological evidence for optimal procedure selection of radical resection for rectal cancer.
Sixty-two patients with low rectal cancer underwent low anterior resection and total mesorectal excision (TME). Surgical specimens were sliced transversely on serial embedded blocks at 2.5-mm intervals, and stained with hematoxylin and eosin (HE). On whole-mount sections the mesorectum was divided into 3 regions: the outer region of the mesorectum (ORM), the middle region of the mesorectum (MRM), and the inner region of the mesorectum (IRM). Microscopic metastatic foci were investigated for metastatic mesorectal region, frequency, types, involvement of the lymphatic system, and correlation with the primary tumor. Tumor-suspect nodules previously considered disease free by HE stain on whole-mount section were examined by in situ hybridization (ISH) on tissue microarray (TMA) through detecting mRNAs of CEA and CK20 with non radioactive biotin-tagged oligonucleotide probes.
Microscopic spread of the tumor was observed in 50.0 percent of patients (31 out of 62, 24 by HE stain on whole-mount section and 7 by ISH on TMA) and that in the ORM was observed in 38.7 percent of the patients (24 out of 62, 16 observed by HE stain on whole-mount section and 8 by ISH on TMA). Microscopic tumor foci spread in the circumferential resection margin (CRM) occurred in 8.1 percent of the patients (5 out of 62, 4 observed by HE stain on whole-mount section and one by ISH on TMA), and distal mesorectum (DMR) involvement was detected in 6.5 percent (4 out of 62, all observed by HE stain on whole-mount section), with the spread extending to within 3 cm from the lower margin of the tumor. Most (26 of 31) of the patients with microscopic spread in mesorectum had TNM Stage III diseases.
The results of the present study support the theory that complete excision of the mesorectum without destruction of the ORM is essential for surgical management of low rectal cancer, and an optimal DMR clearance resection margin of no less than 4 cm was referenced. Five patients with microscopic tumor nodule spread in the CRM observed in the study suggested that microscopic metastases exist in pelvic lateral areas and in the mesorectum simultaneously, indicating the significance of preoperative and/or postoperative radiochemotherapy.
Cancer Investigation 24(4):374-81. · 1.85 Impact Factor
