A statistical model for the identification of genes governing the incidence of cancer with age

The cancer incidence increases with age. This epidemiological pattern of cancer incidence can be attributed to molecular and cellular processes of individual subjects. Also, the incidence of cancer with ages can be controlled by genes. Here we present a dynamic statistical model for explaining the epidemiological pattern of cancer incidence based on individual genes that regulate cancer formation and progression. We incorporate the mathematical equations of age-specific cancer incidence into a framework for functional mapping aimed at identifying quantitative trait loci (QTLs) for dynamic changes of a complex trait. The mathematical parameters that specify differences in the curve of cancer incidence among QTL genotypes are estimated within the context of maximum likelihood. The model provides testable quantitative hypotheses about the initiation and duration of genetic expression for QTLs involved in cancer progression. Computer simulation was used to examine the statistical behavior of the model. The model can be used as a tool for explaining the epidemiological pattern of cancer incidence.     

FAVL impairment of the Fanconi anemia pathway promotes the development of human bladder cancer

Effectiveness of DNA cross-linking drugs in the treatment of bladder cancer suggests that bladder cancer cells may have harbored an insufficient cellular response to DNA cross-link damage, which will sensitize cells to DNA cross-linking agents. Cell sensitivity benefits from deficient DNA damage responses, which, on the other hand, can cause cancer. Many changed cellular signaling pathways are known to be involved in bladder tumorigenesis; however, DNA cross-link damage response pathway [Fanconi anemia (FA) pathway], whose alterations appear to be a plausible cause of the development of bladder cancer, remains an under-investigated area in bladder cancer research. In this study, we found FAVL (variant of FA protein L—FANCL) was elevated substantially in bladder cancer tissues examined. Ectopic expression of FAVL in bladder cancer cells as well as normal human cells confer an impaired FA pathway and hypersensitivity to Mitomycin C, similar to those found in FA cells, indicating that FAVL elevation may possess the same tumor promotion potential as an impaired FA pathway harbored in FA cells. Indeed, a higher level of FAVL expression can promote the growth of bladder cancer cells in vitro and in vivo, which, at least partly, results from FAVL perturbation of FANCL expression, an essential factor for the activation of the FA pathway. Moreover, a higher level of FAVL expression was found to be associated with chromosomal instability and the invasiveness of bladder cancer cells. Collectively, FAVL elevation can increase the tumorigenic potential of bladder cancer cells, including the invasive potential that confers the development of advanced bladder cancer. These results enhance our understanding the pathogenesis of human bladder cancer, holding a promise to develop additional effective tools to fight human bladder cancer.     

FAVL impairment of the Fanconi anemia pathway promotes the development of human bladder cancer

Effectiveness of DNA cross-linking drugs in the treatment of bladder cancer suggests that bladder cancer cells may have harbored an insufficient cellular response to DNA cross-link damage, which will sensitize cells to DNA cross-linking agents. Cell sensitivity benefits from deficient DNA damage responses, which, on the other hand, can cause cancer. Many changed cellular signaling pathways are known to be involved in bladder tumorigenesis; however, DNA cross-link damage response pathway [Fanconi anemia (FA) pathway], whose alterations appear to be a plausible cause of the development of bladder cancer, remains an under-investigated area in bladder cancer research. In this study, we found FAVL (variant of FA protein L—FANCL) was elevated substantially in bladder cancer tissues examined. Ectopic expression of FAVL in bladder cancer cells as well as normal human cells confer an impaired FA pathway and hypersensitivity to Mitomycin C, similar to those found in FA cells, indicating that FAVL elevation may possess the same tumor promotion potential as an impaired FA pathway harbored in FA cells. Indeed, a higher level of FAVL expression can promote the growth of bladder cancer cells in vitro and in vivo, which, at least partly, results from FAVL perturbation of FANCL expression, an essential factor for the activation of the FA pathway. Moreover, a higher level of FAVL expression was found to be associated with chromosomal instability and the invasiveness of bladder cancer cells. Collectively, FAVL elevation can increase the tumorigenic potential of bladder cancer cells, including the invasive potential that confers the development of advanced bladder cancer. These results enhance our understanding the pathogenesis of human bladder cancer, holding a promise to develop additional effective tools to fight human bladder cancer.     

Influence of the war in Croatia on the frequency of gynecological cancer in the University Hospital Osijek in the period from 1985 to 2002

The aim of this study is to estimate the influence of war in Croatia on the frequency of gynecological cancer (cancer of corpus and cervix uteri and ovary) in the Clinical Hospital Osijek, particularly the relation between the pre-war and post-war period. We analyzed 1455 patients with corpus uteri and cervix uteri cancer and ovarian cancer treated in the Clinical Hospital Osijek in the period 1985-2002 (group I). Patients from Osjecko-Baranjska County were analyzed separately--1273 women, (group II) and in the group III there were 182 patients from other counties. The analyzed period was divided into: pre-war 1985-1990, war 1991-1993 and post-war period 1997-2002. In all three groups the number of patients treated for gynecological cancer was significantly larger in the post-war period (group I, N = 611, group II, N = 498, group III, N = 113) than in the pre-war period (group I, N = 457, group II, N = 433, group III, N = 24). The analysis of cancer frequency in relation to the site shows that a total number of patients treated for cervical cancer was larger in the post-war (N = 229) than in the pre-war period (N = 214), but the difference wasn't significant. However, the number of patients from Osjecko-baranjska County treated for cervical cancer was larger in the pre-war (N = 207) than in the post-war period (N = 178) but still, the difference wasn't significant. The number of patients treated for corpus uteri cancer and ovarian cancer was significantly larger for the I group in the post-war (N = 225 and N = 157 respectively) than in the pre-war period (N = 136, and N = 107 respectively). In the group II the number of patients treated for corpus uteri cancer and ovarian cancer was larger in the post-war (N = 196 and N = 124 respectively) than in the pre-war period (N = 130 and N = 96 respectively) but the difference was significant only for corpus uteri cancer. Significantly more women were treated for gynecological cancer in the post-war than in the pre-war period. However, the war had probably an indirect influence on the increased number of patients treated for gynecological cancer mainly because many more women arrived from other counties.     

Increased frequency of the S-allele of the L-myc oncogene in breast cancer

BACKGROUND: Association between restriction fragment length polymorphisms (RFLP) of known oncogenes and a predisposition to develop cancer have been postulated. The L-myc gene is a potential molecular marker associated with cancer susceptibility as well as metastasis, prognosis, and adverse survival. Our aim was to test the hypothesis that there was an association between L-myc S allele in breast cancer and a predisposition to the disease. MATERIALS AND METHODS: The distribution of L-myc polymorphism in 56 patients with breast cancer was determined by polymerase chain reaction-based restriction fragment length polymorphism and compared with that of 51 healthy control subjects. RESULTS: The allele frequencies of L and S in breast cancer patients were 0.70 and 0.30, respectively and those in normal individuals were 0.54 and 0.46, respectively. This difference was primarily the result of a high frequency of the S allele among breast cancer patients compared to controls. The frequency of S allele was significantly higher in breast cancer patients than in normal individuals (p < 0.01). No correlation was observed between the presence of L-myc S allele and several parameters of each patient's history or characteristics of tumor. CONCLUSION: Our results suggested that L-myc polymorphism may be significant in an individual's susceptibility to breast cancer in Turkey and may be useful for identifying patients at high risk of developing breast cancer.     

Consequences of the widespread use of antibiotics

The cancer problem is increasing as life expectancy increases and greater portions of the populace live to the age at which cancer is more likely. Early diagnosis still is difficult. Even with modern methods and with considerable public education with regard to cancer, the disease is often not diagnosed until it is beyond the stage at which cure might be effected. The need for a serodiagnostic test for general screening purposes for cancer detection is tremendous. The major objective of cancer serodiagnostic test methods is to discover a general test that will detect cancer in a high percentage of cases while it is in an early stage; that will give few "false positive" results; that can be done in any laboratory; and that is simple and inexpensive. Many serodiagnostic tests for cancer have been published but none has proven worthy of being a good general test to detect cancer. Yet unless some serodiagnostic test which will be suitable for general screening purposes is developed, it is difficult to see how there can be much improvement in the early diagnosis of cancer, particularly internal cancer. It is hoped that an open-minded attitude will be maintained by physicians on this subject. Recent reports of such a test being developed are encouraging and it is hoped that continued investigations will be confirmatory.     

VEGF-C在结肠癌生长及淋巴转移中的作用

目的：通过观察我院收治的结肠癌患者临床诊断资料,探讨分析血管内皮生长因子-C（VEGF-C）在该疾病患者中的生长以及淋巴转移的作用情况。方法：对我院收治的72例结肠癌患者与同期12例癌旁非癌组织患者,采用免疫组化法检测VEGF-C表达情况。结果：结肠癌与癌旁非癌组织患者的VEGF—C的阳性表达率分别为65-3％与8-3％,对比差异显著（P〈O．05）;VEGF．C在结肠癌中的表达与淋巴转移、浸润深度以及TNM分期情况有关（P〈0．05）。结论：结肠癌患者血管内皮生长因子-C（VEGF-C）的阳性表达率高,具体表达的水平高低与患者的淋巴转移、结肠癌浸润深度以及TNM分期有关,值得临床上进一步探讨与研究。     

Low serum cholesterol level and the risk of cancer of the colon

The study aimed at assessing a degree of low serum cholesterol relationship to carcinoma of the colon. The study involved 137 patients with carcinoma of the colon and 54 patients serving as a control group. Serum cholesterol and total proteins levels were assayed and nutritional status of the patients was analysed. It was found that serum cholesterol was significantly lower in patients with both advanced and mild cancer of the colon in comparison with a control group. Similar tendency was noted in the group of female patients with cancer of the colon but the difference between the patients with not advanced cancer and control group was statistically insignificant. Serum total proteins did not differ in patients with cancer of the colon and control group. In the group of male patients (with both stages of the cancer) in whom low serum cholesterol was noted (below 5.2 mM/L) a risk of cancer was 3-7 times higher. In female patients relative risk of cancer was significantly higher only in the advanced stages of the disease.     

Value of the history in the office diagnosis of breast cancer.

A review of the histories of 1059 patients with breast problems seen consecutively in office consultation revealed an incidence of breast cancer of 13%. Patients over 50 years of age or whose mother or sister had had breast cancer had a substantially greater likelihood of having breast cancer. The finding of the problem on routine examination, a family history of breast cancer in a relative other than the mother or a sister, or prominent breast pain or nipple discharge made the diagnosis of cancer less likely. Menstrual status, a history of previous benign disease, nulliparity, current hormone therapy and duration of symptoms did not help identify the patient likely to have breast cancer. Much time could be saved for both doctor and patient in taking the history from patients with breast disorders. Only the patient''s age and the history of the mother and sisters with regard to breast cancer will help identify the "high-risk" patient. Other historical findings are either valueless or should be used to reassure these usually anxious women.     

Oncomine数据库在肿瘤研究中的应用

Oncomine 是目前世界上最大的癌基因芯片数据库和综合数据挖掘平台之一,该数据库整合了GEO、TCGA和已发表文献来源的RNA和DNA-seq数据。数据库目前含有715个基因表达数据集（datasheet）、86 733个人体肿瘤组织和正常组织样本的信息,且有新的数据不断更新。Oncomine 数据库囊括的肿瘤类型有19种,包括：膀胱癌、脑/中枢神经系统肿瘤、乳腺癌、宫颈癌、结直肠癌、食管癌、胃癌、头/颈肿瘤、肾癌、白血病、肝癌、肺癌、淋巴瘤、黑色素瘤、骨髓瘤、卵巢癌、胰腺癌、前列腺癌、肉瘤。本文就如何利用Oncomine数据库,进行肿瘤组织中癌基因表达差异性分析以及基因共表达分析、癌基因在肿瘤组织中的表达及拷贝数分析、多组研究数据集的荟萃分析（meta analysis）、以及癌基因表达与患者生存率关系等进行分析。通过该数据库可以对肿瘤癌基因进行研究前的筛查,有利于发现新的肿瘤生物标记物或治疗靶点,为临床科学研究奠定一定的理论基础。     

Relationship between the cytologic characteristics of intraperitoneal free cancer cells and the prognosis in patients with gastric cancer

The presence of free cancer cells in the peritoneal cavity of 387 patients with gastric cancer was analyzed using specimens obtained by intraoperative lavage of the pouch of Douglas. If cancer cells were found in the specimen, the case was classified with respect to the number and arrangement (clustered or isolated) of the cancer cells found. Study of the relationship between the histologic type of cancer and the presence of free cancer cells showed that poorly differentiated adenocarcinomas and signet ring-cell carcinomas were associated with a higher incidence of free cancer cells than were other types of cancer. The relationships between the characteristics of the free cancer cells and the postoperative survival rate were also studied. Patients whose free cancer cells were present in clusters were associated with a more favorable prognosis than were those with no such clusters. Patients with small numbers of free cancer cells survived longer than did those with large numbers of free cancer cells.     

Small cell lung cancer: the importance of the extracellular matrix

Lung cancer is the leading cause of cancer deaths in the UK and the small cell lung cancer (SCLC) phenotype is the most aggressive form of this disease, with a high metastatic potential and the development of resistance to chemotherapy. Evidence now suggests that these features may be due to important links between the cancer cells and proteins in their local extracellular matrix (ECM). This article reviews the evidence for a chemoprotective effect of extracellular matrix in small cell lung cancer and discusses the importance of integrin-mediated signalling pathways in this setting.     

Cells of the tumor microenvironment speak the Wnt language

Wnt signaling plays numerous functions in cancer, from primary transformation and tumor growth to metastasis. In addition to these cancer cell-intrinsic functions, Wnt signaling emerges to critically control cross-communication among cancer cells and the tumor microenvironment (TME). Here, we summarize the evidence that not only multiple cancer cell types, but also cells constituting the TME ‘speak the Wnt language’. Fibroblasts, macrophages, endothelia, and lymphocytes all use the Wnt language to convey messages to and from cancer cells and among themselves; these messages are important for tumor progression and fate. Decoding this language will advance our understanding of tumor biology and unveil novel therapeutic avenues.     

Risk of prostate cancer among cancer survivors in the Netherlands

BackgroundIn parallel with increasing numbers of cancer patients and improving cancer survival, the occurrence of second primary cancers becomes a relevant issue. The aim of our study was to evaluate risk of prostate cancer as second primary cancer in a population-based setting.MethodsData from the Netherlands Cancer Registry were used to estimate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for prostate cancer as second primary cancer. The effect of time since first cancer diagnosis, specific first cancer sites, age, and pelvic radiotherapy was taken into account.ResultsOut of 551,553 male patients diagnosed with a first primary cancer between 1989 and 2008, 9243 patients were subsequently diagnosed with prostate cancer. Overall, cancer survivors showed an increased risk (SIR 1.3, 95% CI 1.2–1.3) of prostate cancer. The increased prostate cancer risk was limited to the first year of follow-up for the majority of the specific first cancer sites. More than 10 years after the first cancer diagnosis, only melanoma patients were at increased risk (SIR 1.5, 95% CI 1.2–1.9), while patients with head or neck cancers were at decreased risk (SIR 0.7, 95% CI 0.5–0.9) of being diagnosed with prostate cancer. Patients who underwent primary pelvic radiotherapy for their first cancer had a decreased risk of prostate cancer in the long term (SIR 0.5, 95% CI 0.4–0.6).ConclusionsOur data showed that cancer survivors have an increased prostate cancer risk in the first year following a first cancer diagnosis, which is most likely the result of active screening or incidental detection.     

癌患者血清中癌细胞凝集因子特性的研究

前曾报道癌患者血清中存在选择性凝集具高转移潜能的人鼻咽癌细胞的凝集因子．现除扩大了检测例数外,重点对癌患者血清中凝集因子的化学本质及生物学特性进行了系统研究,证明其可能是一种内源性凝集素（糖结合蛋白质）,特异性识别甘露糖及β1,6分枝的N-乙酰氨基乳糖．其作用不依赖于Ca+,而还原剂可提高其活性并对高碘酸氧化敏感．对这种内源性凝集素在癌栓形成及癌细胞转移中的作用进行了讨论．     

肿瘤干细胞鉴定方法

肿瘤干细胞假说是近年来提出的关于肿瘤发生的新理论,该理论认为肿瘤组织中仅有一小部分细胞可以产生肿瘤并且维持肿瘤生长。在体内外如何鉴定这种具有启动以及保持肿瘤生长的细胞类型,成为肿瘤基础及应用研究的关键问题。目前已经在白血病、乳腺癌、神经胶质瘤等肿瘤中成功鉴定并分离出肿瘤干细胞,这对于肿瘤的临床治疗具有重要意义。本文主要从肿瘤干细胞的鉴定及其在临床研究中的应用等方面进行综述。     

CT与MRI对肝硬化背景下小肝癌检出率的比较

目的:分析比较CT与MR对肝硬化背景下小肝癌检出情况,探究CT与MR在肝硬化背景下小肝癌的诊断价值。方法:选择2010年6月~2015年6月期间,我院收治确诊为肝硬化背景下小肝癌患者91例为研究对象,病理及临床相关方法确诊102个病灶,其中小肝癌69个和微小肝癌33个,患者均在不同时期或序列下行多排螺旋CT与MRI检查,分析比较两者对小肝癌和微小肝癌的检出率。结果:多排螺旋CT检查发现肝癌小病灶91个,其中66个小肝癌,25个微小肝癌;MRI检查发现95个病灶,小肝癌67个,微小肝癌28个;69个小肝癌病灶,检出率最高的为CT动脉期(92.75%)与LAVA动脉期(92.75%),检出率最低的为CT平扫(76.81%);33个微小肝癌病灶,检出率最高为LAVA动脉期(75.76%),检出率最低的为LAVA平衡期(36.36%);CT平扫、门静脉期、动脉期、平衡期、MRI-IN-PHASE、LAVA平衡期、LAVA平扫对小肝癌的检出率显著高于对微小肝癌的检出率(P0.05);CT对小肝癌的检出率显著高于微小肝癌的检出率(P0.05),MRI对小肝癌与微小肝癌的检出率无显著差异(P0.05);MRI与CT对小肝癌的检出率不存在差异(P0.05),但MRI对微小肝癌的检出率显著高于CT(P0.05)。结论:MRI-LAVA的动脉期序列对小肝癌病灶与微小肝癌病灶的检出率最高;CT与MRI在对小肝癌的检出率不存在差异,但MRI对微小肝癌的检出具有更明显的优势。     

Interactions of cancer cells with the microvasculature during metastasis

Metastasis of cancer via the bloodstream is a major factor in the diagnosis, treatment, and prognosis of patients with cancer. Key events in hematogenous metastasis occur in the microvasculature. This is a brief, selective review of some interactions involving cancer cells and the microvasculature in pathological sequence, specifically: 1) intravasation of cancer cells; 2) the arrest of circulating cancer in the microvasculature; 3) cancer cell trauma associated with arrest; 4) microvascular trauma; 5) the inflammatory and 6) coagulative responses associated with arrest; and 7) the fate of arrested cancer cells. The evidence shows that in addition to providing routes for cancer cell dissemination and arrest sites for cancer cell emboli, the microvasculature, through a series of complex interactions with cancer cells, controls the efficiency of and acts as a rate regulator for the metastatic process.     

Cancer of the Breast in Ontario

The breast is the leading cancer site among women; it accounts for 20% of all female cancer deaths. The lifetime probability of death from breast cancer for a female born in Ontario is 3.3%; that is, one in every 30 women will die of breast cancer. The risk of developing breast cancer is almost twice this figure.The medical certificate of death yields a reliable estimate of the number of persons who die of breast cancer, and the level of the age-specific breast cancer death rates has not changed over the past 30 years. Cohort analysis yields an indistinguishable mortality pattern for succeeding cohorts of women from 1871. Available information indicates no change in incidence.The stable mortality and incidence rates suggest that there has been little or no change in the survival rate, despite emphasis on early diagnosis and improvement in therapeutic skills and in technical facilities.