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Bisphosphonates as potential adjuvants for patients with cancers of the digestive system.

ABSTRACT: Best known for their anti-resorptive activity in bone, bisphosphonates (BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor (HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups.

SUBMITTER: Ang C

PROVIDER: S-EPMC4716044 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Bisphosphonates as potential adjuvants for patients with cancers of the digestive system.

Ang Celina C Doyle Erin E Branch Andrea A

World journal of gastroenterology 20160101 3

Best known for their anti-resorptive activity in bone, bisphosphonates (BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has ...[more]

PMID: 26811636

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Suicide rates among patients with cancers of the digestive system.

Project description:ObjectivePrevious studies have suggested that suicide rates are elevated among cancer patients relative to the general population. In this analysis, we comprehensively evaluated characteristics associated with higher suicide rates among patients with cancers of the digestive system.MethodsUsing the United States Surveillance, Epidemiology, and End Results database, we identified all patients diagnosed with digestive system cancers during 2000 to 2014. Patients were classified as having died of suicide if their cause of death in Surveillance, Epidemiology, and End Results was listed as "suicide and self-inflicted injury." Suicide rates were compared to age-, sex-, and race-adjusted rates in the general population.ResultsA total of 881 suicides were identified among 856 293 patients diagnosed with digestive system cancers. The suicide rate in this population was 32.8 per 100 000 person-years and was nearly twice that in the general population (standardized mortality ratio [SMR] = 1.91; 95% CI, 1.79-2.04). Suicide rates were significantly elevated for all cancer sites but were highest for esophageal (SMR = 5.03), pancreatic (SMR = 5.28), stomach (SMR = 2.84), and liver (SMR = 2.14) cancers. Standardized mortality ratios for suicide were highest within the first 5 years of diagnosis and increased with age at diagnosis for all sites except colon and stomach.ConclusionsPatients with cancers of the digestive system have a higher incidence of suicide than the general population. Suicide rates among esophageal and pancreatic cancer patients are more than 5 times general population rates. The involvement of psychiatrists and other mental health professionals may be a critical component of cancer care for these high-risk patient subgroups.

| S-EPMC6584762 | biostudies-literature

Gallstones, cholecystectomy, and risk of digestive system cancers.

Project description:Gallstones and cholecystectomy may be related to digestive system cancer through inflammation, altered bile flux, and changes in metabolic hormone levels. Although gallstones are recognized causes of gallbladder cancer, associations with other cancers of the digestive system are poorly established. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2005), which includes 17 cancer registries that cover approximately 26% of the US population, to identify first primary cancers (n = 236,850) occurring in persons aged ?66 years and 100,000 cancer-free population-based controls frequency-matched by calendar year, age, and gender. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis, adjusting for the matching factors. Gallstones and cholecystectomy were associated with increased risk of noncardia gastric cancer (odds ratio (OR) = 1.21 (95% confidence interval (CI): 1.11, 1.32) and OR = 1.26 (95% CI: 1.13, 1.40), respectively), small-intestine carcinoid (OR = 1.27 (95% CI: 1.01, 1.60) and OR = 1.78 (95% CI: 1.41, 2.25)), liver cancer (OR = 2.35 (95% CI: 2.18, 2.54) and OR = 1.26 (95% CI: 1.12, 1.41)), and pancreatic cancer (OR = 1.24 (95% CI: 1.16, 1.31) and OR = 1.23 (95% CI: 1.15, 1.33)). Colorectal cancer risk associated with gallstones and cholecystectomy decreased with increasing distance from the common bile duct (P-trend < 0.001). Hence, gallstones and cholecystectomy are associated with the risk of cancers occurring throughout the digestive tract.

| S-EPMC5856086 | biostudies-other

Prognostic Value of S100P Expression in Patients With Digestive System Cancers: A Meta-Analysis.

Project description:BackgroundDigestive system cancers (DSCs) are associated with high morbidity and mortality. S100P has been reported as a prognostic biomarker in DSCs, but its prognostic value remains controversial. Accordingly, we conducted a meta-analysis to investigate whether S100P is correlated with overall survival (OS) of patients with DSCs. The relationship between S100P and clinicopathological features was also evaluated.MethodsWe systematically searched PubMed, Embase, Web of Science and Cochrane Library for eligible studies up to January 2020. In total, 16 publications with 1,925 patients were included.ResultsS100P overexpression was associated with poor OS of patient with DSCs (HR=1.54, 95% CI: 1.14-2.08, P=0.005). When stratified by anatomic structure, S100P overexpression was associated with poor prognosis in non-gastrointestinal tract cancers (HR=1.98, 95% CI: 1.44-2.72, P<0.001) but not in gastrointestinal tract cancers (HR=1.09, 95% CI: 0.66-1.81, P=0.727). When stratified by tumor type, S100P overexpression predicted poor OS in cholangiocarcinoma (HR=2.14, 95% CI: 1.30-3.50, P=0.003) and hepatocellular carcinoma (HR=1.91, 95% CI: 1.22-2.99, P =0.005) but not in gastric cancer (HR=0.97, 95% CI: 0.65-1.45, P=0.872), colorectal cancer (HR=1.18, 95% CI: 0.32-4.41, P=0.807), gallbladder cancer (HR=1.40, 95% CI: 0.84-2.34, P=0.198), and pancreatic cancer (HR=1.92, 95% CI: 0.99-3.72, P=0.053). Furthermore, high S100P expression was significantly associated with distant metastasis (OR=3.58, P=0.044), advanced clinical stage (OR=2.03, P=0.041) and recurrence (OR=1.66, P=0.007).ConclusionS100P might act as a prognostic indicator of non-gastrointestinal tract cancers.

| S-EPMC7973272 | biostudies-literature

A retrospective analysis of the prevalence of dental diseases in patients with digestive system cancers.

Project description:The relationship between dental diseases and the prevalence of digestive system cancers remains unclear. The aim of the present study was to examine the prevalence of dental diseases in patients treated for digestive system cancers.The medical and dental records of patients treated for digestive system cancers were retrospectively reviewed, and the results obtained (decayed/filled/missing teeth [DMFT] indices and community periodontal index [CPI] codes) were compared with data from the national survey of dental diseases in order to investigate the relationship between oral health and digestive system cancers.DMFT, D, and F indices were significantly lower, while the M index was slightly higher in digestive system cancer patients than in the national survey. The proportions of individuals with more than 20 residual teeth and denture wearers were significantly lower in cancer patients than in the national survey. The prevalence of periodontitis (CPI codes 3 and 4) and severe periodontitis (CPI code 4) were significantly higher in cancer patients than in the national survey.The present results showed that digestive system cancers were closely associated with multi-tooth loss and/or a low denture-wearing rate. The prevalence of severe periodontitis was also found to be higher in cancer patients. These results suggest that periodontitis and associated multi-tooth loss play a potential role in digestive system cancers.

| S-EPMC6455988 | biostudies-literature

The Regulatory Functions of Circular RNAs in Digestive System Cancers.

Project description:Circular ribonucleic acids (circRNAs), which are a type of covalently closed circular RNA, are receiving increasing attention. An increasing amount of evidence suggests that circRNAs are involved in the biogenesis and development of multiple diseases such as digestive system cancers. Dysregulated circRNAs have been found to act as oncogenes or tumour suppressors in digestive system cancers. Moreover, circRNAs are related to ageing and a wide variety of processes in tumour cells, such as cell apoptosis, invasion, migration, and proliferation. Moreover, circRNAs can perform a remarkable multitude of biological functions, such as regulating splicing or transcription, binding RNA-binding proteins to enable function, acting as microRNA (miRNA) sponges, and undergoing translated into proteins. However, in digestive system cancers, circRNAs function mainly as miRNA sponges. Herein, we summarise the latest research progress on biological functions of circRNAs in digestive system cancers. This review serves as a synopsis of potential therapeutic targets and biological markers for digestive system cancer.

| S-EPMC7140005 | biostudies-literature

Predictive role of XRCC5/XRCC6 genotypes in digestive system cancers.

Project description:Cancers are a worldwide concern; oral, esophageal and gastrointestinal cancers represent important causes of cancer-related mortality and contribute to a significant burden of human health. The DNA repair systems are the genome caretakers, playing a critical role in the initiation and progression of cancers. However, the association between the genomic variations of DNA repair genes and cancer susceptibility is not well understood. This review focuses on the polymorphic genotypes of the non-homologous end-joining DNA repair system, highlighting the role of two genes of this pathway, XRCC5 and XRCC6, in the susceptibility to digestive system cancers and discussing their potential contributions to personalized medicine.

| S-EPMC3251741 | biostudies-literature

Circulating vitamin C and digestive system cancers: Mendelian randomization study.

Project description:Background & aimsVitamin C is an antioxidant with a potential role in the prevention of digestive system cancers, but there is yet no consensus whether vitamin C has a causal role in these cancers. The aim of this study was to utilize Mendelian randomization to decipher the potential causal associations of vitamin C with risk of digestive system cancers.MethodsTen genetic variants previously found to be significantly associated with circulating vitamin C were used as instrumental variables. Effect size estimates for the genetic associations of the vitamin C-associated genetic variants with six major malignancies of digestive system were obtained from the FinnGen (N = 309 154) and UK Biobank (N = 367 542) studies. Results from the two studies were combined using meta-analysis.ResultsGenetically predicted higher circulating vitamin C showed a suggestive association with lower risk of small intestine and colorectal cancer after accounting for multiple testing. The odds ratio per 1 standard deviation increment in circulating vitamin C was 0.55 (95% confidence interval 0.32-0.94; P = 0.029) for small intestine cancer and 0.84 (95% confidence interval 0.73-0.96; P = 0.013) for colorectal cancer. There was a suggestive association between genetically predicted higher circulating vitamin C with lower risk of liver cancer in FinnGen but no association in the meta-analysis (odds ratio 0.69; 95% CI 0.36-1.32; P = 0.265). Genetically predicted circulating vitamin C was not associated with cancers of the esophagus, stomach, or pancreas.ConclusionThis Mendelian randomization study indicates that vitamin C might play a role in the prevention of small intestine and colorectal cancer.

| S-EPMC7613472 | biostudies-literature

The role of hypoxia-inducible factor-2 in digestive system cancers.

Project description:Hypoxia is an all but ubiquitous phenomenon in cancers. Two known hypoxia-inducible factors (HIFs), HIF-1α and HIF-2α, primarily mediate the transcriptional response to hypoxia. Despite the high homology between HIF-1α and HIF-2α, emerging evidence suggests differences between both molecules in terms of transcriptional targets as well as impact on multiple physiological pathways and tumorigenesis. To date, much progress has been made toward understanding the roles of HIF-2α in digestive system cancers. Indeed, HIF-2α has been shown to regulate multiple aspects of digestive system cancers, including cell proliferation, angiogenesis and apoptosis, metabolism, metastasis and resistance to chemotherapy. These findings make HIF-2α a critical regulator of this malignant phenotype. Here we summarize the function of HIF-2 during cancer development as well as its contribution to tumorigenesis in digestive system malignancies.

| S-EPMC4669763 | biostudies-other

Prognostic value of CSN5 in patients with digestive system cancers: a systematic review and meta-analysis.

Project description:BackgroundDespite the understanding of the COP9 signalosome subunit 5 (CSN5) in tumor genesis, there is no conclusive evidence on its value to predict the survival and prognosis of digestive system tumor patients. Hence this study aimed to evaluate the impact of CSN5 levels on the survival and clinicopathological parameters of digestive system neoplasm patients.MethodsFirst, a comprehensive search was conducted in four databases. We utilized the Hazard Ratio (HR) with a 95% confidence interval (CI) to evaluate the prognostic value of CSN5 for the overall survival (OS) and recurrence-free survival (RFS) of patients. Then, we estimated the connection between CSN5 and the clinicopathological parameters based on the Odds Ratio (OR) with the corresponding 95% CI.ResultsThis meta-analysis included 22 studies and 2193 patients diagnosed with digestive system tumors. High expression of CSN5 was correlated to poorer OS (HR = 2.28, 95% CI: 1.71-3.03; p < 0.00001). Additionally, high CSN5 levels were correlated with worse invasion depth (OR = 0.49, 95% CI: 0.25-0.96, p = 0.04), positive lymphatic metastasis (OR = 0.28, 95% CI: 0.16-0.47, p = 0.00001), positive distant metastasis (OR = 0.32, 95% CI: 0.13-0.76, p = 0.01) and poorer differentiation degree (OR = 0.34, 95% CI: 0.19-0.60, p = 0.0003). However, we did not detect a correlation between CSN5 expression and age, gender, tumor stage, tumor size or vascular invasion. Furthermore, no significant publication bias was detected.ConclusionThis meta-analysis demonstrated that the overexpression of CSN5 level might foresee poorer OS in digestive system cancer patients. Additionally, CSN5 levels might be related to the prognosis of digestive system tumors.

| S-EPMC9308938 | biostudies-literature

Genetically predicted circulating B vitamins in relation to digestive system cancers.

Project description:BackgroundFolate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations.MethodsTwo, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants.ResultsGenetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (ORSD, 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (ORSD 1.16; 95% CI 1.06, 1.26, p = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined ORSD was 1.16 (95% CI 1.08, 1.25, p < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer.ConclusionsThese results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer.

| S-EPMC8184856 | biostudies-literature

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