CD105、CD34基因蛋白在宫颈鳞状细胞癌中的表达及临床意义

目的:探讨CD105、CD34在子宫颈鳞状细胞癌中的表达及临床病理学特征的相关性。方法:MW抗原修复LSAB免疫组织化学染色方法检测60例子宫颈癌切片中CD105、CD34的表达。结果:CD105标记的血管条数(36.23±10.21)比CD34(42.17±9.43)敏感,能突出显示较小的、不成熟的微血管或单一的内皮细胞,但差异无显著性(P>0.05)。微血管密度与年龄、肿瘤大小、部位、肿瘤大体类型及分化程度等临床病理学特征无明显关系(P>0.05),CD105标记的微血管密度(MVD)与宫颈鳞状细胞癌的FIGO分期和淋巴结转移密切相关(P<0.05)。结论:CD105抗体对检测肿瘤微血管更具有特异性,CD105标记的MVD可能是宫颈鳞状细胞癌患者的一个独立的预后指标。

Relationship between proliferative activity of cancer cells and clinicopathological factors in patients with esophageal squamous cell carcinoma

AIM: To assess whether the molecular markers of malignant tumors could improve the understanding of tumor characteristics, and to observe the characteristics of expression of cell cycle markers Ki-67 and cyclin A in esophageal carcinoma and to analyze the relationship between proliferative activity of cancer cells and clinicopathological factors. METHODS: Seventy of surgically resected esophageal squamous cell carcinoma (SCC) were examined by immun-ohistochemistry utilizing commercially available antibodies. Nuclear staining was regarded as a positive result. At least 50 fields in each tumor and non-tumor section were evaluated at a medium power (×200) to determine the proportion of tumor cells and the staining intensity of nuclei in the entire sections. RESULTS: Ki-67 and cyclin A were only expressed in base cells of normal esophageal mucosa. The positive immuno-staining of nuclei of SCC was significantly higher than that in normal esophageal mucosa (t = 13.32 and t = 7.52, respectively, P<0.01). The distribution of positively stained was more diffuse and stronger in poorly differentiated SCC. Both Ki-67 and cyclin A expressions were related to histological grades of tumors (t = 3.5675 and t = 3.916; t = 2.13, respectively, P<0.05) but not to the sex and age of the patients, tumor size, lymphatic invasion, location, or stage grouping. CONCLUSION: The proliferative activity of cancer cells may be understood by immunohistochemistry of Ki-67 and cyclin A in Chinese patients with esophageal SCC. These cell cycle markers may serve as an indicator of cancer cell proliferation rate. The overexpression of cell cycle markers Ki-67 and cyclin A suggests the poor SCC differentiation in patients with esophageal carcinoma.

GSTM1,GSTT1,GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population:Different pattern of squamous cell carcinoma and adenocarcinoma

AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.

Esophagus and regenerative medicine

In addition to squamous cell carcinoma,the incidence of Barrett's esophagus with high-grade dysplasia and esophageal adenocarcinoma is rapidly increasing worldwide.Unfortunately,the current standard of care for esophageal pathology involves resection of the affected tissue,sometimes involving radical esophagectomy.Without exception,these procedures are associated with a high morbidity,compromised quality of life,and unacceptable mortality rates.Regenerative medicine approaches to functional tissue replacement include the use of biological and synthetic scaffolds to promote tissue remodeling and growth.In the case of esophageal repair,extracellular matrix(ECM) scaffolds have proven to be effective for the reconstruction of small patch defects,anastomosis reinforcement,and the prevention of stricture formation after endomucosal resection(EMR).More so,esophageal cancer patients treated with ECM scaffolds have shown complete restoration of a normal,functional,and disease-free epithelium after EMR.These studies provide evidence that a regenerative medicine approach may enable aggressive resection of neoplastic tissue without the need for radical esophagectomy and its associated complications.

Synchronous incidental gastrointestinal stromal and epithelial malignant tumors

AIM:To investigate the incidence of incidental gastrointestinal stromal tumor (GIST) and its etiopathogenesis.METHODS: From January 1, 2000 to December 31, 2007, 13 804 cases of gastrointestinal epithelial malignant tumor (EMT) and 521 cases of pancreatic adenocarcinoma (PAC) were successfully treated with surgery at the Department of General Surgery and the Department of Thoracic Surgery, West China Hospital, Sichuan University, China. The clinical and pathologic data of 311 cases of primary GIST, including 257 cases with clinical GIST and 54 cases of incidental GIST were analyzed.RESULTS: Of the 311 patients, 54 had incidental GIST, accounting for 17.4%. Of these tumors, 27 were found in 1.13% patients with esophageal squamous cell carcinoma (ESCC), 22 in 0.53% patients with gastric adenocarcinoma (GAC), 2 in 0.38% patients with PAC, 2 in 0.03% patients with colorectal adenocarcinoma, and 1 in one patient with GAC accompanying ESCC, respectively. Patients with incidental GIST presented symptoms indistinguishable from those with EMT. All incidental GIST lesions were small in size, and the majority had a low mitotic activity while only 1.9% (5/257) of clinical GIST lesions had a high risk.CONCLUSION: Incidental GIST may occur synchronously with other tumors and has a high prevalence in males. Surgery is its best treatment modality.

Metastatic basaloid-squamous cell carcinoma of the esophagus treated by 5-fluorouracil and cisplatin

Basaloid squamous cell carcinoma （BSC） of the esophagus is a rare malignant disease. We report here a patient with recurrent esophageal BSC, who was successfully treated by systemic chemotherapy containing 5-fluorouracil （5-FU） and cisplatin （CDDP）. A 57-year-old woman was diagnosed as having SCluamous cell carcinoma of the esophagus upon endoscopic examination. Curative esophagectomy with lymph node dissection was performed under the thoracoscope. The pathological diagnosis of the surgical specimen was BSC. Five months after operation, the patient was diagnosed as having a recurrence of the BSC with metastases to the liver and spleen, and a right paraclavicular lymph node. She was given systemic chemotherapy consisting of continuous infusion of 800 mg/d of 5-FU and 3 h infusion of 20 mg/d of CDDP for 5 consecutive days every 4 wk. The metastatic lesions in the spleen and right paraclavicular lymph node disappeared, and the liver metastasis was apparently reduced in size after 2 courses of chemotherapy. The tumor regression was seen over 6 courses, with progression afterwards. Although subsequent treatment with CPT-11 and CDDP was not effective, docetaxel and vinorelbine temporarily controlled the tumor growth for 2 mo. 5-FU and CDDP combination may be useful for the patients with advanced BSC.

New approach to anal cancer:Individualized therapy based on sentinel lymph node biopsy

Oncological treatment is currently directed toward a tailored therapy concept.Squamous cell carcinoma of the anal canal could be considered a suitable platform to test new therapeutic strategies to minimize treatment morbidity.Standard of care for patients with anal canal cancer consists of a combination of radiotherapy and chemotherapy.This treatment has led to a high rate of local control and a 60% cure rate with preservation of the anal sphincter,thus replacing surgical abdominoperineal resection.Lymph node metastases represent a critical independent prognostic factor for local recurrence and survival.Mesorectal and iliac lymph nodes are usually included in the radiation field,whereas the inclusion of inguinal regions still remains controversial because of the subsequent adverse side effects.Sentinel lymph node biopsies could clearly identify inguinal node-positive patients eligible for therapeutic groin irradiation.A sentinel lymph node navigation procedure is reported here to be a feasible and effective method for establishing the true inguinal node status in patients suffering from anal canal cancer.Based on the results of sentinel node biopsies,a selective approach could be proposed where node-positive patients could be selected for inguinal node irradiation while node-negative patients could take advantage of inguinal sparing irradiation,thus avoiding toxic side effects.

A Controlled Study on Comparing Differences in CT Perfusion Imaging between Rabbits inoculated with VX2 Lung Tumor and Patients with Squamous Cell Carcinoma of the Lung

OBJECTIVE By analysis and evaluation of the perfusion images and perfusion parameters of the rabbits with VX2 lung tumor, the association between the perfusion parameters and tumor angiogenesis of patients with squamous cell carcinoma of the lung has been studied in order to establish a non-invasive and effective way to detect tumor blood supply, which is be able to exhibit hemodynamic data in tumors during cancer treatments. METHODS Fifteen Netherlands rabbits inoculated with VX2 lung tumor （rabbit group） and 25 patients with squamous cell carcinoma of the lung （patient group） received a multi-slice spiral CT perfusion imaging test using the Netherlands PHILIPS Brilliance 16-slice spiral CT and a U.S. MEDRAD binocular highpressure syringe. Image postprocessing was done using the special perfusion software and EBW 4.0 Workstation. Perfusion volume （PV）, peak enhanced increment （PEI）, transit time peak （TTP）, and blood volume （BV） were measured and analyzed. RESULTS In the rabbit group, the values of the PV, PEI, TTP, and BV of the tumor margin were （53.89 ± 13.38） mL/（min.mL）, （45.71 ± 15.52） Hu, （39.29 ± 10.10） sec, and （31.45 ± 18.19） mL/100 g, respectively; these values of the tumor center were （36.57 ± 14.17） mL/（min.mL）, （28.64 ± 11.74） Hu, （39.00 ＋ 9.78） sec, and （19.76 ± 13.95） mL/100 g, respectively; the values of the muscles were （12.45± 4.38） mL/（min.mL）, （10.98 ± 5.03） Hu, （38.86 ± 10.04） sec, and （5.38 ±2.87） mL/100 g, respectively. The values of the relative perfusion volume （RPV）, relative peak enhanced increment （RPEI）, and relative blood volume （RBV） of the tumor margin were 4.38 ± 1.45, 3.96± 1.45, 9.99 ± 11.7, respectively; these values of the tumor center were 2.14 ± 1.08, 1.83±1.45, 4.17 ±3.39, respectively. The values of the PV, PEL BV of the tumor margin vs. the values of the muscles developed t-values, which were 15.028, 10.79, and 5.88, respectively （P ≤ 0.01）, with statistical significance; the values of the PV, PEI, BV of the tumor center vs. the values of the muscles produced t-values, which were 8.67, 7.49, and 4.55, respectively （P 〈 0.01）, with statistical significance. The values of the TTP of the tumor margin vs. TTP values of the muscles, and the TTP values of the tumor center vs. TTP values of the muscles developed t-values, which were 1.7 and 0.806, respectively （P ≥ 0.05）, without statistical significance. In the patient group, the values of the PV, PE, TTP, and BV of the tumor margin were （88.95 ± 30.89） mL/（min.mL）, （61.87 ± 27.31） Hu, （37.72 ± 12.53） sec, and （18.38 ± 7.2） mL/100 g, respectively; these values of the tumor center were （39.77 ± 18.29） mL/（min.mL）, （14.57 ± 8.1） Hu, （35.64 ± 12.41） sec, and （11.22 ± 6.02） mL/100 g, respectively; these values of the muscles were （12.45 ± 6.5） mL/（min.mL）, （6.14 ± 2.66） Hu, （35.68± 12.35） sec, and （2.23 ± 1.11） mL/100 g, respectively. The values of the RPV, RPEI, and RBV of the tumor margin were 8.05 ± 5.04, 8.87 ± 4.32, and 12.16 ± 8.49, respectively; these values of the tumor center were 2.39 ± 1.68, 2.97 ± 2.1, 3.53 ± 2.82, respectively. The values of the PV, PEI, BV of the tumor margin in the patient group vs. the values of the muscles produced t-values, which were 13.8, 10.85, and 12.22, respectively （P 〈 0.01）, with significant differences; these values of the tumor center vs. the values of the muscles developed t-values, which were 9.158, 6.26, 8.654, respectively （P 〈 0.01）, with significant differences. The TTP value of the tumor margin vs. that of the muscles produced t-value, which was 0.371, and the TTP value of the tumor center vs. that of the muscles developed t-value, which was 1 （P 〉 0.05）, without statistical difference. CONCLUSION CT perfusion imaging technics demonstrates directly dynamic changes of blood flow to tumors, which assists in identifying tumor growth and necrosis, therefore, this research provides an evidence-based guidelines for the treatment of human lung squamous cell carcinoma and has far-reaching clinical significance.

Reconstruction of composite defects of the nose following tumor resection–a single author's experience and evaluation of the outcome

Objective:The aim of the study was to present our experience in reconstruction of complex defects of the nose.Methods:Fourteen patients presenting with large composite defects of the nose were anatomically reconstructed after full tumor clearance of a skin cancer.The aesthetic outcome was assessed subjectively and objectively while the functional outcome was only assessed subjectively in 13 patients.Results:Basal cell carcinoma(BCC),represented the tumor excised in 10 patients while the remaining 4 patients suffered from squamous cell carcinoma(SCC).One patient died of extensive local recurrence of SCC after 6 months.The commonest flap used for inner lining was the septal flap while the forehead paramedian flap provided the external coverage for the majority of patients.All flaps survived completely except in one patient who developed distal paramedian forehead flap necrosis.Two patients developed multiple abscesses and sinuses discharging parts of cartilage grafts through the flaps’skin with one patient suffering from total extrusion of the costal cartilage grafts.Two other patients suffered from severe nostril stenosis.All patients had variable degree of difficulty in airway passage,while most patients were satisfied with the total nasal appearance.The objective assessment of the overall appearance of the nose scored less than the subjective satisfaction.Conclusion:Reconstruction of complex nasal defects has a high learning curve.Intranasal flaps are usually of limited size and nostril asymmetry is likely to occur.Local or regional skin flaps if available are still considered a good choice for inner as well as outer lining.

Change and Signif icance of Mitochondrial DNA Copy Number in Esophageal Squamous Cell Carcinoma

OBJECTIVE To compare the differences of mitochondrial DNA (mtDNA) copies among the tissues of esophageal squamous cell carcinoma (ESCC), para-neoplastic tissue and normal mucous membrane of the esophagus, and to study the relationship between the mtDNA and the occurrence and devel- opment of esophageal squamous cell carcinoma. METHODS The mtDNA copies of 42 specimens with the ESCC, paraneoplastic mucous tissue and normal mucous membrane of the esophagus were determined using real-time fluorescence quantitative PCR. The mtDNA was analyzed using agarose gel electrophoresis. RESULTS The mtDNA from all of the tissues (42/42) from the ESCC, para-neoplastic tissue and normal esophageal mucous membranes was analyzed, showing that there were an average mtDNA copy number of 27.1894×106 μg DNA, 9.4102×106 μg DNA and 5.9347×106 μg DNA, from the respective tissues. There were signifi cant differences (F=27.83, P<0.05) in mtDNA copy number among the three. A positive band was shown at 403 bp after gel electrophoresis of the PCR products, and the lane where the ESCC mtDNA located was rather bright, which was in accordance with the result of the real-time PCR determination. CONCLUSION An increase in the mtDNA copy number is related to the occurrence and development of ESCC.

The clinical features of thoracic stomach cancer after surgical treatment for esophageal carcinoma

Objective:Postoperative recurrence of esophageal carcinoma was the main factor that affect the patients' survival and quality of life.This study mainly investigated the clinical features of thoracic stomach cancer (TSC) after surgical treatment for esophageal carcinoma.Methods:We retrospectively reviewed 51 cases of postoperative TSC in our hospital (Henan Province Tumor Hospital,Zhengzhou,China).Results:The 51 (10.97%) of all 465 cases that underwent endoscope after surgical treatment for esophageal carcinoma in our hospital were TSCs.There were 13 cases with complicating anastomotic recurrence.The locations of 46 cases (90.2%) were the same as the primary cancer.The 48 cases were squamous cell carcinomas and 3 cases were adenocarcinomas after esophagectomy for esophageal carcinoma.Endoscopic manifestations were puffiness-infiltrating type at 39.2% (20/51),massive type at 15.7% (8/51),ulcerative type at 7.8% (4/51) and ulcerative infiltrating type at 3.9% (2/51) and stenotic type etc.Conclusion:The incidence of TSC after surgical treatment for esophageal carcinoma is high.The main cause was that the local residual cancer invaded gastric wall.The gastroscopic features of TSC are different from those of gastric cancer.Regular review with endoscopy in postoperative esophageal carcinoma patients was a major way to diagnose TSC.

Inhibition of human esophageal squamous cell carcinomas by targeted silencing of tumor enhancer genes: an overview

Esophageal cancer has been reported as the ninth most common malignancy and ranks as the sixth most frequent cause of death worldwide. Esophageal cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy. Novel strategies are needed to boost the oncologic outcome. Recent advances in the molecular biology of esophageal cancer have documented the role of genetic alterations in tumorigenesis. Oncogenes serve a pivotal function in tumorigenesis. Targeted therapies are directed at the unique molecular signature of cancer cells for enhanced efficacy with low toxicity. RNA interference(RNAi) technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. Related results have shown that targeting oncogenes with siRNAs, specifically the mRNA, effectively reduces tumor cell proliferation and induces apoptotic cell death. This article will briefly review studies on silencing tumor enhancer genes related to the induction of esophageal cancer.

Basaloid squamous cell carcinoma of the esophagus: an immunohistochemical study of 8 cases

Objective To explore the biological features of basaloid squamous cell carcinoma (BSC) of the esophagus.Methods Cytokeratins (CK4, CK18 and CK19), epithelial membrane antigen (EMA), carcino embryoantigen (CEA), α-smooth muscle antigen (α-SMA), S-100, laminin (LN), collagen Ⅳ (Col-Ⅳ), neuralspecific enolase (NSE), proliferating cell nuclear antigen (PCNA) and p53 antibodies were used to detect the corresponding antigen expression in 8 cases of BSC with ABC immunohistochemical methods.Results Two kinds of BSC cell components have different responses to the above antibodies. For basaloid cells (BCs), 7 cases were positive for CK19, and were negative for the other 4 epithelial antibodies CK4, CK18, CEA and EMA. BCs of 4 cases were positive to the muscular antibodies α-SMA and S-100, and the hyaline degeneration in the tumor nests was positive for LN and Col-Ⅳ. BCs had a high index of PCNA, with an average level of 54%. For squamous cells (SCs), 7 cases were positive for the epithelial antigen CK4, CEA and EMA, but were negative for CK19, α-SMA and S-100. The index of PCNA of SC was low, with an average level of 25%.Conclusion BSC of the esophagus is a high-malignancy tumor which is of multi-oriented differentiation.BCs represent basal cells which have the tendency of myoepithelial differentiation and have strong proliferation ability, whereas SCs represent typical squamous cell differentiation.

miR-29b upregulates miR-195 by targeting DNMT3B in tongue squamous cell carcinoma

MicroRNAs play important roles in the devel- opment and progression of various cancers, including tongue squamous cell carcinoma （TSCC）. miR-29b and miR-195 have been reported to be tumor suppressors in TSCC. Here, we investigated the expression of miR-29b and miR- 195 and their relationship in TSCC. Our data showed that miR-29b and miR-195 were significantly downregulated in TSCC com- pared with their matched nonmalignant tissues in 60 paired samples. The level of miR-29b was positively correlated with that of miR-195 in TSCC and the matched nonmalignant tissues. Moreover, miR-29b overexpression induced the demethylation of CpG islands upstream of miR-195 via targeting DNMT3B, leading to the upregulation of miR-195 in TSCC cell lines. Following DNMT3B silencing, the expression of miR-195 was increased and the methylation of CpG islands upstream of miR-195 was reduced. Although overexpression of miR-29b alone significantly increased miR- 195 expression, co-transfection of miR-29b with DNMT3B resulted in no change in miR-195 expression. Taken together, our results demonstrated that miR-29b could upregulate miR- 195 by directly targeting DNMT3B in TSCC. The interaction between miR-29b and miR-195 might provide new insights in developing novel therapeutic approaches of TSCC.