口腔癌术后短期内死亡原因及DNA定量分析

目的：通过对口腔癌短期内死亡病例的分析，了解死亡原因与肿瘤分明、治疗手段、病理分级、DNA定量分析的关系，以规范治疗，提高生存率。方法：93例用平阳霉素化疗，总量160mg／10只天，38例用DDP30mg、5Fu750mg连续化疗5天，加放射治疗DГ4500cGy，26例颞浅动脉插管化疗，共用DDP120mg，5Fu3750mg，MTX40mg，均采用联合根治术，下颌切除或方块切除，同期手术修复105例。DNA定量分析采用真彩色图像分析统计，检测样本为Feulgen染色的石蜡切片。结果：术前治疗除7例T3、T4稍，其余原发肿瘤均缩小1／2左右。7例原发灶复发，1例肺部转移。DNA含量分析，峰值在近2倍体处，1例在5倍体外，死亡与非死亡病例的DNA含量无差异。结论：死亡原因与分期、手术切除范围、切缘是否癌残留及综合治疗关系密切，同期手术整复有利于彻底切除和功能恢复，与病理分级及DNA多倍体含量无明显关系。     

Heterogeneity of DNA Ploidy Pattern in Carcinoma of the Gallbladder: Primary and Metastatic Sites

There are few detailed reports on the heterogeneity of the nuclear DNA ploidy pattern in carcinoma of the gallbladder. We studied twelve autopsied cases who died of extended gallbladder carcinoma. Multiple samples were taken from the primary site (Pri), from direct invasion of the liver ( Hin f), from hematogenous metastasis to the liver (H), from lymphatic metastasis (LN) and from peritoneal dissemination (P). The DNA ploidy pattern was investigated by image cytometry. Heterogeneity of the DNA ploidy pattern in Pri, Hin f, H, LN and P was found in 7/11, 2/10, 5/10, 2/6 and 3/6 cases, respectively. Aneuploidy was more frequently found in Hin f than at the Pri. The DNA index of Hin f was significantly higher than that of Pri. Several stcmlincs, with different quantities of DNA, were found in Pri. Most of these stemlines were also observed in other sites. These facts may suggest that polyclonal cancer cells rather than one cancer cell or monoclonal cancer cells of a Pri metastasize or infiltrate, and that various polyclonal cancer cells proliferate to different degrees under different circumstances.     

Demographic Profile of p16 Immunopositive and HPV DNA PCR Positive Oral Squamous Cell Carcinoma in a Large Cohort of Indian Patients

Background: The Indian subcontinent has the highest incidence of oral cavity squamous cell carcinoma in the world. The high incidence of tobacco chewing habit with or without smoking has been found to be the chief culprit. However in a minor subset of patients Human Papilloma Virus may play a role. Materials and Methods: A total of 800 cases of Oral squamous cell carcinoma were included in the study. The patients were given a questionnaire comprising of questions about demographic details and habits. The biopsy samples were routinely processed for immunohistochemistry for p16 (E6H4 clone, CINtec histology, Roche diagnostics). Cases with 2+/3+ positive nuclear staining with more than 75% cells immunopositive were taken as p16 immunopositive as per the AJCC criteria and were further subjected to HPV DNA PCR for which DNA was extracted from the formalin fixed paraffin embedded tissue. Results: Out of 800 OSCC cases 139 (17.37%) showed p16 immunopositivity by AJCC criteria. Out of these, 104 (104/139, 74.8%) cases were positive by HPV DNA PCR for HPV-16/18. Following patient characteristics were associated with a higher proportion of p16 and HPV DNA positivity–urban residence, vegetarian diet, illiteracy, graduate or higher education. No correlation was noted with gender, tobacco smoking or chewing habits, religion, occupation or site of tumor. The p16 immunopositivity was higher in the younger age group with no tobacco habits. Conclusion: A significant proportion of OSCC cases in India are associated with HPV infection. A higher percentage of p16 immunopositivity amongst younger patients with no tobacco habits points towards a distinct subset of patients in whom HPV may be the chief culprit and not just playing a supporting role.     

Heterogeneity in gastric carcinoma with special reference to DNA content and mitotic activity: histopathologic differentiation.

DNA ploidy and mitotic activity were microspectrophotometrically investigated in 46 patients with gastric carcinoma. Measurements of DNA content and mitotic index (M.I.) were examined in the mucosal, submucosal, muscularis propria, and serosal layers of tumors, respectively. The frequency of cells with values exceeding hexaploid chromosome (6c) and mitotic counting analysis revealed a significant higher value in serosa, compared with findings in the mucosa. This tendency was not evident in cases of a differentiated type adenocarcinoma but was noted in those with the undifferentiated type. There were 37 tumors (80.0%) with the same DNA distribution patterns in every layer of the stomach (homogeneous DNA ploidy). Heterogeneity of DNA ploidy was observed in nine tumors (20.0%). Carcinoma with a heterogeneous DNA ploidy manifested a significantly higher incidence of metastasis to the lymph nodes than did those with homogeneous type. Characteristically, there was venous permeation preponderance in the differentiated type and peritoneal dissemination preponderance in the undifferentiated type. This evidence of DNA heterogeneity in gastric carcinoma tissues suggests a possible correlation with the metastatic behavior.     

DNA疫苗诱导的小鼠抗肿瘤特异性细胞免疫和体液免疫

目的:检测以双表达质粒pIRES为载体构建的带有全序列癌胚抗原(CEA)基因和IL-2基因的核苷酸疫苗对机体特异性抗肿瘤免疫反应的激活效果。方法:利用分子生物学技术,将CEA基因片段和IL-2基因片段连接于真核双表达质粒pIRES中,用肌内注射方法接种核酸疫苗;检测疫苗在小鼠肌肉组织中的表达情况及其对小鼠脾细胞CEA特异性细胞免疫和体液免疫反应的激活效果。结果:小鼠经肌内注射质粒后,免疫组化证实该核酸疫苗可在体内有效表达CEA分子;免疫检测显示注射后小鼠血清中出现抗CEA抗体,脾细胞IL-4分泌增强,特异性淋巴细胞增值反应明显并伴有自然杀伤细胞NK活性显著增高。结论:实验所构建的核酸疫苗pIRES-CEA,pIRES-IL-2,pIRES-IL-2等可在小鼠体内高效表达并表现出良好的免疫原性。     

Optimal follow-up duration for evaluating objective response to radiotherapy in patients with hepatocellular carcinoma:a retrospective study

The time to complete or partial (objective) response to radiotherapy in patients with hepatocellular carcinoma (HCC) is variable; thus, the reported frequency of these responses depends on the length o...     

贲门癌胃癌根治术前动脉灌注美蓝标记的临床应用

作者采用介入放射学方法，对１２例消化道癌症病人行术前动脉灌注美蓝染色标记，其中胃癌７例，贲门癌５例。除１例胃癌患者，因癌广泛转移未能手术外，其余１１例均行根治手术，术中共清扫淋巴结８４组计１９１个，癌转移淋巴结６８个，占清扫淋巴结的３５．６％，癌转移淋巴结染色率１００％。病灶及淋巴结染色后呈鲜艳水蓝色，本法可清楚显示病灶范围和所在区域淋巴结，可验证术中是否彻底切除病灶，也为清扫范围提供了依据。除以     

Individual and Integrated Effects of Potential Risk Factors for Oral Squamous Cell Carcinoma: A Hospital-Based Case- Control Study in Jazan,Saudi Arabia

Background: Oral cancer is the sixth most common cancer in the world, with a high prevalence reported in Jazanprovince of Saudi Arabia. The objectives of this study were to check individual and integrated effects of potential riskfactors for oral squamous cell carcinoma. Materials and methods: A case control study was designed with a sampleof 210 subjects, in which histopathologically confirmed incident cases (n=70) and controls (n=140) matched for age,gender and referral route, were recruited. Differences in exposure to potential risk factors between cases and controlswere assessed using chi-square and McNemar analyses. A logistic regression model with interactions was applied to checkindividual and integrated effects. Results: Mean age of the sample was 55 years (+ 20 years). Shammah (O.R = 33.01;C.I = 3.22 – 39.88), shisha (O.R = 3.96; C.I = 0.24 – 63.38), and cigarette (O.R = 1.58; C.I = 0.13, 2.50) consumptionwas significantly associated (P<0.05) with oral squamous cell carcinoma development. In contrast, Khat chewing (O.R= 0.67; C.I = 0.19-2.36) was without significant effect. An increase in odds ratios was observed when combinationsof shammah and shisha (O.R = 35.03; C.I = 11.50-65.66), shisha and cigarettes (O.R = 10.52; C.I = 1.03 – 33.90) orshamma and cigarettes (O.R = 10.10; C.I = 0.50 - 20.40) were used. Conclusion: Combined exposure to risk-factorshas serious implications and policies on oral cancer prevention should be designed with attention to this aspect.     

Epithelial Dysplasia at Excision Margins of Oral Squamous Cell Carcinoma: A Review on Relationship to Clinicopathological Parameters and Prognosis

Background: Epithelial dysplasia (ED) at oral cancer excision margins is a frequent finding. Dysplastic epithelium at excision margins may not be similar to dysplasia in Oral potentially malignant disorders (OPMD) as malignant transformation has already taken place. Therefore, management of ED at excision margins should be different to that of OPMD. ED creates a dilemma in relation to further management of cancer patients, since there are no accepted guidelines. Therefore, the objective of this review is to analyze  existing literature and to arrive at evidence based recommendations for the management of ED at excision margins. Methods: A comprehensive string was run on PubMed, Medscape and Medline. The final outcome included 113 studies. Finally, the most relevant 10 articles were critically assessed for inclusion and exclusion criteria against various parameters. Results and Conclusions:  Severe and Moderate ED need re-excision in order to improve prognosis. There is not enough sound evidence for the management of Mild ED at excision margins of oral squamous cell carcinoma. Guidelines for the management of ED at excision margins should be formulated after comprehensive multi center studies using lager cohorts of patients.     

Assessment of the Blood Parameters,Cardiac and Liver Enzymes in Oral Squamous Cell Carcinoma Following Treated with Injectable Doxorubicin-Loaded Nano-Particles

Purpose: Oral squamous cell carcinoma (OSCC) is the most common and most malignant disorder of the oralcavity. Standard cancer treatments have many complications for patients. Nausea, vomiting, and perturbation inblood cells are the most common side effects when using Doxorubicin (Dox) for the treatment of OSCC. Use ofDoxorubicin-loaded nano-particles (n-Dox) give rise to increase its biological efficacy and the rapeutic effects. This studyassessed the efficacy of the injectable form of the n-Doxon blood parameters and cardiac and liver enzymes comparedto the commercial form of Dox in OSCC-induced by 4NQO in rats. Methods: 4-nitroquinoline-1-oxideas was used asa solution in drinking water for inducing OSCC during 14 weeks in male Sprague-Dawley rats. Four groups of animalswere categorized randomly: first (OSCC+Dox), second (OSCC+n-Dox), third (OSCC) and, last, healthy animals. Results:Using n-Dox had no harmful effect on the number of white and red blood cells. Thrombocytopenia and leukopenia inanimals treated with n-Dox was less than the other groups. Hemoglobin and hematocrit in all treated groups did notdiffer and were similar to the healthy control. Hepatic and cardiac enzymes did not show any significant difference inany of the groups. Conclusion: The results of this research showed that significant decreases in haematological changesoccurred, including leukopenia and anemia, in an animal model of OSCC induced by 4-NQO following use of n-Doxwith compare to Dox. Use of n-Dox is better than of Dox for treatment of OSCC.     

Outcomes of Post-Operative Treatment with Concurrent Chemoradiotherapy (CRT) in High-Risk Resected Oral Cavity Squamous Cell Carcinoma (OCSCC): A Multi-Institutional Collaboration

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I–IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m² cisplatin dose (p < 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (<200 mg/m²) vs. 20.8 months (≥200 mg/m²). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m² was associated with improved DFS in high-risk resected OCSCC pts.     

A Correlative Study of N-Cadherin Expression with Different Grades of Oral Squamous Cell Carcinoma Projecting as a Marker of Epithelial to Mesenchymal Transition in Tumor Progression

Background: Epithelial cells typically express E-cadherin where as N-cadherin expressed by mesenchymal cells.The epithelial to mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-celladhesion, and gain migratory and invasive properties to become mesenchymal cells. EMT is typical for carcinoma cellsduring tumor progression and correlate with the local invasiveness and metastatic potential of the tumor. Oral squamouscell carcinoma is a malignant neoplasm arising from the mucosal epithelium of the oral cavity. It can be classifiedas well; moderate and poor depends on a tumor cells resemblance to its tissue of origin. Materials and Methods: Atotal of 130 cases of histopathologically diagnosed as OSCC were selected for the study, out of which 66,38 and 26were well, moderate and poorly differentiated respectively. One section was stained with Haematoxylin and Eosinand the other section for N-cadherin immunohistochemical study. Then the N-cadherin expression was correlatedhistopathologically with different grades of OSCC. Statistical analysis was carried out mainly by Chi-Square analysis.Results: Among the 66 cases of WDSCC mean value of N-cadherin expression was 1.79, 38 cases of MDSCC meanvalue of N-cadherin expression was 4.16 and among the 26 cases of PDSCC the mean value was 6.38.That means thevalue of N- cadherin expression was progressively increasing with decreased differentiation of the tumor cells. Thestatistical analysis also shown it was highly significant (P<0.001). Conclusion: A correlative study of N-cadherinexpression with different grades of OSCC will be useful to predict the state of tumor progression and also it may giveaccuracy for histopathogical grading of the tumor.     

Nuclear DNA content and prognosis in human breast cancer: A static cytophotometric study

Summary Nuclear DNA content was measured by static cytophotometry in smears from breast carcinomas from 80 women, and the results were correlated with other prognostic variables and survival using multivariate statistical analysis. 49% of patients had diploid tumors and 51% hyperdiploid tumors. There was a strong correlation between DNA ploidy and axillary lymph node status, tumor size, ER status, and short term survival (median follow-up 40 months). Of all parameters measured, ploidy showed the strongest correlation with survival, and was a significant prognostic indicator even when other prognostic factors were taken into account.     

Altered methionine metabolism and global DNA methylation in liver cancer: relationship with genomic instability and prognosis

Mounting evidence underlines the role of genomic hypomethylation in the generation of genomic instability (GI) and tumorigenesis, but whether DNA hypomethylation is required for hepatocellular carcinoma (HCC) development and progression remains unclear. We investigated the correlation between GI and DNA methylation, and influence of methionine metabolism deregulation on these parameters and hepatocarcinogenesis in c-Myc and c-Myc/Tgf-alpha transgenic mice and human HCCs. S-adenosyl-L-methionine/S-adenosylhomocysteine ratio and liver-specific methionine adenosyltransferase (MatI/III) progressively decreased in dysplastic and neoplastic liver lesions developed in c-Myc transgenic mice and in human HCC with better (HCCB) and poorer (HCCP) prognosis (based on patient's survival length). Deregulation of these parameters resulted in a rise of global DNA hypomethylation both in c-Myc and human liver lesions, positively correlated with GI levels in mice and humans, and inversely correlated with the length of survival of HCC patients. No changes in MATI/III and DNA methylation occurred in c-Myc/Tgf-alpha lesions and in a small human HCC subgroup with intermediate prognosis, where a proliferative activity similar to that of c-Myc HCC and HCCB was associated with low apoptosis. Upregulation of genes involved in polyamine synthesis, methionine salvage and downregulation of polyamine negative regulator OAZ1, was highest in c-Myc/Tgf-alpha HCCs and HCCP. Our results indicate that alterations in the activity of MAT/I/III, and extent of DNA hypomethylation and GI are prognostic markers for human HCC. However, a small human HCC subgroup, as c-Myc/Tgf-alpha tumors, may develop in the absence of alterations in DNA methylation.     

Carcinoma in situ of the breast: correlation of histopathology to immunohistochemical markers and DNA ploidy

In a consecutive and unselected series of 178 cases of carcinoma in situ of the breast (CIS), comprising both ductal (DCIS) and lobular type (LCIS), and a series of 48 cases of invasive carcinoma (IC) with predominance of DCIS, the association between histopathology, immunohistochemical markers (ER, PgR, MIB-1, c-erbB-2, and p53), and DNA ploidy was investigated, in order to discriminate biologically different groups. In DCIS, significant correlation was shown between large nuclear size and comedonecrosis, both of which showed also strong association to DNA aneuploidy, high proliferation activity, low steroid receptor content, and overexpression of c-erbB-2 and p53 – factors that may indicate an aggressive behavior. Small nuclear CIS, whether LCIS or DCIS, on the contrary, were DNA diploid with low proliferation, and no cases showed overexpression of c-erbB-2 and p53. Heterogeneity with respect to the investigated parameters was also a frequent finding that may reflect a development complexity. In IC, comparison of the DCIS and the invasive component showed similar patterns. No significant differences were shown between DCIS without and with invasion. This may indicate that none of the investigated parameters on its own are essential for the event of invasion.     

KRT13, FAIM2 and CYP2W1 mRNA Expression in Oral Squamous Cell Carcinoma Patients with Risk Habits

Background: Expression of KRT13, FAIM2 and CYP2W1 appears to be influenced by risk habits, thusexploring the associations of these genes in oral squamous cell cancer (OSCC) with risk habits, clinico-pathologicalparameters and patient survival may be beneficial in identifying relevant biomarkers with different oncogenicpathways. Materials and Methods: cDNAs from 41 OSCC samples with and without risk habits were includedin this study. Quantitative real-time PCR was used to analyze KRT13, FAIM2 and CYP2W1 in OSCC. Thehousekeeping gene (GAPDH) was used as an endogenous control. Results: Of the 41 OSCC samples, KRT13was down-regulated in 40 samples (97.6%), while FAIM2 and CYP2W1 were down-regulated in 61.0% and48.8%, respectively. Overall, there were no associations between KRT13, FAIM2 and CYP2W1 expression withrisk habits, selected socio-demographic and clinico-pathological parameters and patient survival. Conclusions:Although this study was unable to show significance, there were some tendencies in the associations of KRT13,FAIM2 and CYP2W1 expression in OSCC with selected clinic-pathological parameters and survival.