A minimum version of log-rank test for testing the existence of cancer cure using relative survival data

Cancer survival is one of the most important measures to evaluate the effectiveness of treatment and early diagnosis. The ultimate goal of cancer research and patient care is the cure of cancer. As cancer treatments progress, cure becomes a reality for many cancers if patients are diagnosed early and get effective treatment. If a cure does exist for a certain type of cancer, it is useful to estimate the time of cure. For cancers that impose excess risk of mortality, it is informative to understand the difference in survival between cancer patients and the general cancer-free population. In population-based cancer survival studies, relative survival is the standard measure of excess mortality due to cancer. Cure is achieved when the survival of cancer patients is equivalent to that of the general population. This definition of cure is usually called the statistical cure, which is an important measure of burden due to cancer. In this paper, a minimum version of the log-rank test is proposed to test the equivalence of cancer patients' survival using the relative survival data. Performance of the proposed test is evaluated by simulation. Relative survival data from population-based cancer registries in SEER Program are used to examine patients' survival after diagnosis for various major cancer sites.     

胃癌干细胞研究进展

胃癌是仅次于肺癌的第二大致死率癌症,尽管近年来对胃癌研究有了很大进展,但由于缺乏良好的动物模型,对胃癌的发病机理仍然不是很清楚.近年的研究表明,肿瘤组织不是由均一细胞构成的,其中存在一些少量细胞可以自我更新并可以分化为肿瘤组织的其他细胞,这类细胞具有类似成体组织干细胞（tissue stem cells）的特性称之为肿瘤干细胞（cancer stem cells）.肿瘤干细胞被认为在肿瘤的生长、转移、复发中发挥着重要作用.有证据表明在胃癌组织中存在胃癌干细胞（gastric cancer stem cells）,但是对胃癌干细胞的来源仍然不是十分明确.对肿瘤干细胞的研究有助于癌症的治疗,改变目前药物针对所有癌细胞的治疗策略.     

早期胃癌的治疗现状与进展

胃癌是常见的消化道肿瘤之一,是我国死亡率最高的恶性肿瘤之一。与日本韩国等发达国家相比,我国胃癌患者多数在就诊时已处于进展期,早期胃癌所占比例不足10%。传统的开腹胃癌手术仍是治疗早期胃癌的主要手段。相较于传统开腹手术,腹腔镜手术对于早期胃癌的治疗优势是显而易见的。早期胃癌患者行腹腔镜手术,具有术后恢复快,生活质量好,近期疗效佳等优势。内镜黏膜下剥离术(ESD,endoscopic submucosal dissection)是近年来出现的一项新的治疗早期胃癌的手段。本文就传统开腹手术、腹腔镜手术及ESD分别在早期胃癌治疗中的应用进行了综述。微创手术治疗早期胃癌将逐渐代替开腹手术,成为早期胃癌治疗的主要手段。     

Cancer Mortality in People Treated with Antidepressants before Cancer Diagnosis: A Population Based Cohort Study

BackgroundDepression is common after a cancer diagnosis and is associated with an increased mortality, but it is unclear whether depression occurring before the cancer diagnosis affects cancer mortality. We aimed to study cancer mortality of people treated with antidepressants before cancer diagnosis.ConclusionsInitiation of antidepressive treatment prior to cancer diagnosis is common and is associated with an increased mortality.     

The future burden of cancer in Canada: Long-term cancer incidence projections 2013–2042

BackgroundCancer is the leading cause of death in Canada and the estimated annual spending associated with cancer is approximately $7.5 billion. Projecting the future burden of cancer in Canada is essential for health planning and evaluation. We aimed to estimate the future incidence of cancer in Canada to 2042.MethodsAge-sex-region-specific cancer incidence data were obtained for the years 1983-2012 and cancer incidence was projected from 2013 to 2042 for the top five cancer sites. The modelling algorithm combined a mixture of cancer projection methods to select the best-fitted model. When the chosen model produced by the modelling algorithm resulted in estimates that were not consistent with expert opinion, an alternate model was selected that took into consideration historical changes in policy, screening and lifestyle behaviours. Incidence projections were made for Canada and its provinces.ResultsLung cancer incidence is estimated to rise to 14,866 cases in men and 19,162 in women in 2042. Colorectal cancer incidence is estimated to rise to 28,146 in men and 21,102 in women. Cases of bladder cancer are projected to rise to 10,708 and 3,364 in men and women, respectively. Breast cancer incidence is predicted to rise to 40,712 and prostate cancer incidence is projected to rise to 92,949.ConclusionThese cancer incidence projections up to 2042 can be used for planning cancer control strategies and prevention programs. Given the ongoing changes in the prevalence of risk factors and in cancer prevention policies, these estimates should be interpreted with caution.     

饮食和生活习惯与胃癌的相关性研究进展

胃癌是起源于胃粘膜上皮细胞的恶性肿瘤。近年来,虽然大部分国家胃癌发生率呈下降趋势,但我国胃癌的发病率和死亡率仍居高不下。胃癌的发生是多因素共同参与的复杂过程,如与种族、遗传、年龄、性别、幽门螺旋杆菌感染、饮食等因素相关,其中饮食及生活习惯被认为与胃癌的发生关系密切。而且早期胃癌的预后相对良好,降低发生率是防治胃癌的一项关键措施。因此,通过了解饮食及生活习惯因素与胃癌之间的关系,可以加强胃癌的一级预防,从而改善胃癌患者预后。本文就高盐、高脂饮食,蛋白质、蔬菜水果摄入以及吸烟、饮酒等因素与胃癌关系的研究进展进行综述,以期对胃癌的预防奠定一定基础。     

Transforming growth factor-β signaling,a potential mechanism associated with diabetes mellitus and pancreatic cancer?

Pancreatic cancer is a common malignant digestive disease. Epidemiological and clinical studies have demonstrated that pancreatic cancer is closely related to diabetes mellitus. Diabetic patients are more likely to develop pancreatic cancer, which is linked with poor outcomes. Pancreatic cancer is complicated with abnormal blood sugar and insulin resistance and promotes the development of diabetes mellitus. Understanding the molecular mechanisms linking diabetes mellitus and pancreatic cancer is essential for the treatment of diabetes cancer patients. The transforming growth factor-β (TGF-β) signaling pathway is deregulated in cancer and has a dual role in different stages of cancer as a suppressor or a promoter. More important, The TGF-β signaling pathway is also another important reason for diabetic complications. This review summarizes the relationship between diabetes and pancreatic cancer, in particular, focusing on the role of the TGF-β signaling pathway. It is possible to find drugs like metformin that can prevent and treat pancreatic cancer by targeting the TGF-β signaling pathway.     

Genetic epidemiology of prostate cancer

A family history of prostate cancer is a consistent risk factor for prostate cancer, and can also be used to predict the presence of prostate cancer among asymptomatic men who undergo PSA screening. Approximately 5% of cases of prostate cancer have a familial component. The genetic epidemiology of prostate cancer is complex, and genes on chromosome 1 and X chromosome contribute to familial aggregation. Neither of these prostate cancer susceptibility genes have been identified, but are the subject of an active search. Hereditary prostate cancer resembles non-hereditary prostate cancer in terms of age of onset, pathologic appearance and grade.     

HER-2/Epstein-Barr virus crosstalk in human gastric carcinogenesis: A novel concept of oncogene/oncovirus interaction

Gastric cancer is the fourth most common cancer and the second leading cause of cancer deaths worldwide. Additionally, it is well-known that metastatic cancer disease is a major cause of morbidity and mortality in cancer patients. Several investigations reported that HER-2 (ErbB-2 receptor) and Epstein-Barr virus (EBV) are important etiological factors in human gastric cancer, where either oncogene/oncovirus alone can derive a major event of cancer progression and metastasis via epithelial–mesenchymal transition (EMT). Herein, we discuss, for the first time, the possibility of HER-2/EBV-oncoproteins interaction in human gastric cancer initiation and/or progression.     

Risk of prostate,ovarian, and endometrial cancer among relatives of women with breast cancer.

OBJECTIVE--To investigate the risk of prostate, ovarian, and endometrial cancer among relatives of patients with breast cancer. DESIGN--Cohort study of 947 pedigrees in which the proband had breast cancer, linked with the Icelandic cancer registry. SETTING--Iceland. SUBJECTS--The 947 pedigrees included 29,725 people, of whom 1539 had breast cancer, 467 had prostate cancer, 135 ovarian cancer, and 105 endometrial cancer. MAIN OUTCOME MEASURES--Risk of prostate, ovarian, and endometrial cancer among blood relatives of women with breast cancer compared with risk in spouses. RESULTS--The risk of prostate cancer was significantly raised for all relatives (1.5), first degree relatives (1.4), and second degree relatives (1.3) of women with breast cancer. Risk of ovarian cancer was raised for all relatives (1.9) and first degree relatives (1.9) and risk of endometrial cancer was raised for all relatives only (1.9). The risk of prostate cancer was raised if the proband with breast cancer had a first degree relative with prostate cancer. CONCLUSIONS--Coaggregation exists between breast cancer and cancers of the prostate, ovaries, and endometrium. This risk relation is probably based on genes which act by increasing the risk for cancer at these sites. Environmental factors that are common among relatives may also play a part. Continued research is required into pathophysiological mechanisms that could explain these observations.     

与卵巢癌转移有关的microRNA研究进展

卵巢癌是女性生殖系统三大恶性肿瘤之一,其致死率居于各类妇科肿瘤之首,是严重影响妇女生命的重要疾患,卵巢癌的转移则是造成病人死亡的重要因素。近年来随着microRNA（又称miRNA或微RNA）作为一种小分子非编码RNA被发现,证实miRNA的作用与各类肿瘤有着重要的联系,这些肿瘤包括乳腺癌、食管癌、胰癌、口腔癌等。近几年的研究表明,miRNA可以影响卵巢癌的发生与发展,并与其转移也存在着紧密的关系。与卵巢癌转移有关的miRNA作用机制的揭示,将会为转移性卵巢癌的诊断及治疗提供新的途径。本综述在通过检索近年来最新文献的基础上,对于卵巢癌的转移机理进行了详尽的分析,并对miRNA在卵巢癌转移中的重要研究予以了详细的阐述。     

Characterization of the ptr5+ gene involved in nuclear mRNA export in fission yeast

Lung cancer is the leading cause of cancer related deaths worldwide. It is necessary to better understand the molecular mechanisms involved in lung cancer in order to develop more effective therapeutics for the treatment of this disease. Recent reports have shown that Wnt signaling pathway is important in a number of cancer types including lung cancer. However, the role of Frizzled-8 (Fzd-8), one of the Frizzled family of receptors for the Wnt ligands, in lung cancer still remains to be elucidated. Here in this study we showed that Fzd-8 was over-expressed in human lung cancer tissue samples and cell lines. To investigate the functional importance of the Fzd-8 over-expression in lung cancer, we used shRNA to knock down Fzd-8 mRNA in lung cancer cells expressing the gene. We observed that Fzd-8 shRNA inhibited cell proliferation along with decreased activity of Wnt pathway in vitro, and also significantly suppressed A549 xenograft model in vivo (p<0.05). Furthermore, we found that knocking down Fzd-8 by shRNA sensitized the lung cancer cells to chemotherapy Taxotere. These data suggest that Fzd-8 is a putative therapeutic target for human lung cancer and over-expression of Fzd-8 may be important for aberrant Wnt activation in lung cancer.     

The role of Snail in prostate cancer

Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of death from cancer in men. Epithelial-mesenchymal transition (EMT) is a process by which cancer cells invade and migrate, and is characterized by loss of cell-cell adhesion molecules such as E-cadherin and increased expression of mesenchymal proteins such as vimentin; EMT is also associated with resistance to therapy. Snail, a master regulator of EMT, has been extensively studied and reported in cancers such as breast and colon; however, its role in prostate cancer is not as widely reported. The purpose of this review is to put together recent facts that summarize Snail signaling in human prostate cancer. Snail is overexpressed in prostate cancer and its expression and activity is controlled via phosphorylation and growth factor signaling. Snail is involved in its canonical role of inducing EMT in prostate cancer cells; however, it plays a role in non-canonical pathways that do not involve EMT such regulation of bone turnover and neuroendocrine differentiation. Thus, studies indicate that Snail signaling contributes to prostate cancer progression and metastasis and therapeutic targeting of Snail in prostate cancer holds promise in ?future.     

The role of Snail in prostate cancer

Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of death from cancer in men. Epithelial-mesenchymal transition (EMT) is a process by which cancer cells invade and migrate, and is characterized by loss of cell-cell adhesion molecules such as E-cadherin and increased expression of mesenchymal proteins such as vimentin; EMT is also associated with resistance to therapy. Snail, a master regulator of EMT, has been extensively studied and reported in cancers such as breast and colon; however, its role in prostate cancer is not as widely reported. The purpose of this review is to put together recent facts that summarize Snail signaling in human prostate cancer. Snail is overexpressed in prostate cancer and its expression and activity is controlled via phosphorylation and growth factor signaling. Snail is involved in its canonical role of inducing EMT in prostate cancer cells; however, it plays a role in non-canonical pathways that do not involve EMT such regulation of bone turnover and neuroendocrine differentiation. Thus, studies indicate that Snail signaling contributes to prostate cancer progression and metastasis and therapeutic targeting of Snail in prostate cancer holds promise in �future.     

Proteins are potent biomarkers to detect colon cancer progression

Colon cancer is the most common type of cancer and major cause of death worldwide. The detection of colon cancer is difficult in early stages. However, the secretory proteins have been used as ideal biomarker for the detection of colon cancer progress in cancer patients. Serum/tissue protein expression could help general practitioners to identify colon cancer at earlier stages. By this way, we use the biomarkers to evaluate the anticancer drugs and their response to therapy in cancer models. Recently, the biomarker discovery is important in cancer biology and disease management. Also, many measurable specific molecular components have been studied in colon cancer therapeutics. The biomolecules are mainly DNA, RNA, metabolites, enzymes, mRNA, aptamers and proteins. Thus, in this review we demonstrate the important protein biomarker in colon cancer development and molecular identification of protein biomarker discovery.     

Advances of MUC1 as a target for breast cancer immunotherapy

MUC1 is a potential target in breast cancer immunotherapy as MUC1 is overexpressed in breast cancer, and is absent or expressed in low level in normal mammary gland. In addition, MUC1 is mostly aberrantly underglycosylated in cancer and the antigens on the cancer surface are different from normal cell. Therefore targeting MUC1 for cancer immunotherapy can exploit the difference between cancer and normal cells, and eliminating the cancerous cells while leaving the normal mammary cells unharmed. This review will focus on the recent advance of MUC1 breast cancer immunotherapy currently being investigated.     

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.     

Alpha B‐crystallin promotes the invasion and metastasis of gastric cancer via NF‐κB‐induced epithelial‐mesenchymal transition

Alpha B‐crystallin (CRYAB) is overexpressed in a variety of cancers. However, little is known about its specific function and regulatory mechanism in gastric cancer. Here, we first explore the role of CRYAB in gastric cancer progression and metastasis. The expression of CRYAB was determined by western blot and immunohistochemistry in gastric cancer tissues. Besides, methods including stably transfected against CRYAB into gastric cancer cells, western blot, migration and invasion assays in vitro and metastasis assay in vivo were also conducted. The expression of CRYAB is up‐regulated in gastric cancer tissues compared with matched normal tissues. High expression level of CRYAB is closely correlated with cancer metastasis and shorter survival time in patients with gastric cancer. Additionally, CRYAB silencing significantly suppresses epithelial‐mesenchymal transition (EMT), migration and invasion of gastric cancer cells in vitro and in vivo, whereas CRYAB overexpression dramatically reverses these events. Mechanically, CRYAB facilitates gastric cancer cells invasion and metastasis via nuclear factor‐κ‐gene binding (NF‐κB)‐regulated EMT. These findings suggest that CRYAB expression predicts a poor prognosis in patients with gastric cancer. Besides, CRYAB contributes to gastric cancer cells migration and invasion via EMT, mediated by the NF‐κB signalling pathway, thus possibly providing a novel therapeutic target for gastric cancer.     

Prohibitin promotes androgen receptor activation in ER-positive breast cancer

Prohibitin (PHB) is an evolutionarily conserved protein with multiple functions in both normal and cancer cells. Androgen receptor (AR) was reported to act as a different role in the ER-positive and ER-negative breast cancer. However, little is known about the role of PHB and whether PHB could regulate AR expression in the ER-positive breast cancer. Here, we determined the expression and clinical outcomes of PHB in breast cancer samples using 121 breast cancer tissues and published databases, and investigated the role of PHB in breast cancer cell growth, apoptosis and cell cycle arrest in the ER-positive breast cancer cells. We obtained the expression of PHB is significantly low in breast cancer samples, and low PHB expression positively correlated with poor prognosis of breast cancer. We detected that PHB could inhibit breast cancer cell proliferation, change cell cycle distribution and promote cell apoptosis in the ER-positive breast cancer cells. Moreover, we found PHB could significantly increase AR expression in both mRNA and protein levels in the ER-positive breast cancer cells. Additionally, a significant positive correlation between PHB and AR expression was identified in the 121 breast cancer tissues. PHB and AR expression are associated with prognosis in the ER-positive breast cancer patients. Our results indicate that PHB promotes AR activation in ER-positive breast cancer, making PHB and AR potential molecular targets for ER-positive breast cancer therapy.     

Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium.

Dominant predisposition to early-onset breast cancer and/or ovarian cancer in many families is known to be the result of germ-line mutations in a gene on chromosome 17q, known as BRCA1. In this paper we use data from families with evidence of linkage to BRCA1 to estimate the age-specific risks of breast and ovarian cancer in BRCA1-mutation carriers and to examine the variation in risk between and within families. Under the assumption of no heterogeneity of risk between families, BRCA1 is estimated to confer a breast cancer risk of 54% by age 60 years (95% confidence interval [CI] 27%-71%) and an ovarian cancer risk of 30% by age 60 years (95% CI 8%-47%). Similar lifetime-risk estimates are obtained by examining the risks of contralateral breast cancer and of ovarian cancer, in breast cancer cases in linked families. However, there is significant evidence of heterogeneity of risk between families; a much better fit to the data is obtained by assuming two BRCA1 alleles, one conferring a breast cancer risk of 62% and an ovarian cancer risk of 11% by age 60 years, the other conferring a breast cancer risk of 39% and an ovarian cancer risk of 42%, with the first allele representing 71% of all mutations (95% CI 55%-87%). There is no evidence of clustering of breast and ovarian cancer cases within families.