Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review focuses on the application of drug-loaded nanoparticles (NPs), also called therapeutic NPs, to combat cancer chemoresistance. Many cancer patients have encouraging response to first line chemotherapies but end up with cancer progression or cancer recurrence that requires further treatment. Response to subsequent chemotherapies with various agents usually drops significantly due to formidable cancer chemoresistance. A number of mechanisms have been postulated to account for cancer chemoresistance or poor response to chemotherapy. The best studied mechanism of resistance is mediated through the alteration in the drug efflux proteins responsible for the removal of many commonly used anticancer drugs. Therapeutic NPs have emerged as an innovative and promising alternative of the conventional small molecule chemotherapies to combat cancer drug resistance and have shown enhanced therapeutic efficacy and reduced adverse side effects as compared to their small molecule counterparts. Here the possible mechanisms of therapeutic NPs to combat cancer chemoresistance are reviewed, including prolonging drug systemic circulation lifetime, targeted drug delivery, stimuli-responsive drug release, endocytic uptake of drugs and co-delivering chemo-sensitizing agents. We also call attention to the current challenges and needs of developing therapeutic NPs to combat cancer drug resistance.
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PMID:Therapeutic nanoparticles to combat cancer drug resistance. 2021 78

Exciting new studies are increasingly strengthening the link between mitochondrial mutagenesis and tumor progression. Here we provide a comprehensive review and meta-analysis of studies reporting on mitochondrial DNA mutations in common human cancers. We discuss possible mechanisms by which mitochondrial DNA mutations may influence carcinogenesis, outline important caveats for interpreting the detected mutations--particularly differentiating causality from association--and suggest how new mutational assays may help resolve fundamental controversies in the field and delineate the origin and expansion of neoplastic cell lineages. Finally, we discuss the potential clinical utility of mtDNA mutations for improving the sensitivity of early cancer diagnosis, rapidly detecting cancer recurrence, and predicting the disease outcome.
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PMID:Generation, function, and prognostic utility of somatic mitochondrial DNA mutations in cancer. 2054 83

The possibility that anesthetic drugs can influence cancer recurrence rate is a subject of recent interest. Based on early in vitro data demonstrating opiates on breast cancer xenografts and two recent epidemiologic studies suggesting differences in recurrence rates in both breast and prostate cancer contingents dependent on whether patients received a combined regional-general anesthetic or a general anesthetic with opioid analgesia, there has been recent interest in the role of the micro-opioid receptor (MOR) in angiogenesis and oncogenic signaling. We recently demonstrated that morphine causes reciprocal transactivation of the MOR and VEGF receptors and that MOR-knockout mice do not develop significant tumors when injected with lung cancer cells as do their wild-type controls. Furthermore, infusion of the peripheral MOR antagonist methylnaltrexone markedly attenuates tumor growth in experimental mouse models. These experimental data support the hypothesis that opioids affect tumor progression and suggest the MOR as a potential target for chemotherapeutic drugs.
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PMID:Effect of perioperative opioids on cancer recurrence: a hypothesis. 2079 70

In contrast to hematological malignancies, meaningful improvements in survival statistics for patients with malignant brain tumors have not been realized in >40 years of clinical research. Clearly, a new medical approach to brain cancers is needed. Recent research has led to a new concept that needs to destroy all cancer subclones to control the cancer progression. However, this new concept fails to distinguish the difference between dominating subclones and dormant subclones. Here, we address the issue of clonal switch and emphasize that there may be one or more than one dominant clones within the tumor mass at any time. Destructing one dominant clone triggers activating other dormant subclones to become dominating subclones, causing cancer progress and post-treatment cancer recurrence. We postulate the concept of subclonal switchboard signaling and the pathway that involved in this process. In the context of stem cell and development, there is a parallel with the concept of quiescent/dormant cancer stem cells (CSC) and their progeny, the differentiated cancer cells; these 2 populations communicate and co-exist. The mechanism with which determines to extend self-renewal and expansion of CSC is needed to elucidate. We suggest eliminating the "dominating subclonal switchboard signals" that shift the dormant subclones to dominating subclones as a new strategy.
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PMID:Control dominating subclones for managing cancer progression and posttreatment recurrence by subclonal switchboard signal: implication for new therapies. 2193 25

Surgery for the removal of a primary tumor presents an opportunity to eradicate cancer or arrest its progression, but is also believed to promote the outbreak of pre-existing micrometastases and the initiation of new metastases. These deleterious effects of surgery are mediated through various mechanisms, including psychological and physiological neuroendocrine and paracrine stress responses elicited by surgery. In this review we (i) describe the many risk factors that arise during the perioperative period, acting synergistically to make this short timeframe critical for determining long-term cancer recurrence, (ii) present newly identified potent immunocyte populations that can destroy autologous tumor cells that were traditionally considered immune-resistant, thus invigorating the notion of immune-surveillance against cancer metastasis, (iii) describe in vivo evidence in cancer patients that support a role for anti-cancer immunity, (iv) indicate neuroendocrine and paracrine mediating mechanisms of stress- and surgery-induced promotion of cancer progression, focusing on the prominent role of catecholamines and prostaglandins through their impact on anti-cancer immunity, and through direct effects on the malignant tissue and its surrounding, (v) discuss the impact of different anesthetic approaches and other intra-operative procedures on immunity and cancer progression, and (vi) suggest prophylactic measures against the immunosuppressive and cancer promoting effects of surgery.
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PMID:Surgery and stress promote cancer metastasis: new outlooks on perioperative mediating mechanisms and immune involvement. 2250 92

Obesity and components of energy imbalance, that is, excessive energy intake and suboptimal levels of physical activity, are established risk factors for cancer incidence. Accumulating evidence suggests that these factors also may be important after the diagnosis of cancer and influence the course of disease, as well as overall health, well-being, and survival. Lifestyle and medical interventions that effectively modify these factors could potentially be harnessed as a means of cancer control. However, for such interventions to be maximally effective and sustainable, broad sweeping scientific discoveries ranging from molecular and cellular advances, to developments in delivering interventions on both individual and societal levels are needed. This review summarizes key discussion topics that were addressed in a recent Institute of Medicine Workshop entitled, "The Role of Obesity in Cancer Survival and Recurrence"; discussions included (i) mechanisms associated with obesity and energy balance that influence cancer progression; (ii) complexities of studying and interpreting energy balance in relation to cancer recurrence and survival; (iii) associations between obesity and cancer risk, recurrence, and mortality; (iv) interventions that promote weight loss, increased physical activity, and negative energy balance as a means of cancer control; and (v) future directions.
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PMID:The role of obesity in cancer survival and recurrence. 2269 35

MicroRNAs are small non-coding RNA regulators of gene expression that play important roles in critical biological processes, including cell division, self-renewal and cell state maintenance. Their deregulation leads to extensive clinical consequences in tumorigenesis. Cancers demonstrate heterogeneity in their cell states implicated in their resistance and resurgence. Apart from proliferating cells, cancers harbor a small proportion of assorted quiescent cells that resist conventional therapeutics and contribute to cancer recurrence. MicroRNA expression, targets, microRNPs (microRNA-protein complexes) and their functions have been demonstrated to be regulated in distinct tumor cell states and as an adaptive response to stress signals in tumor-unfavorable environments. In turn, altered microRNPs and their modified post-transcriptional mechanisms of gene expression may contribute to tumor resistance and influence tumor progression. An understanding of distinct microRNA mechanisms in cancer cells would provide extensive insights into the versatile roles of microRNAs in the perpetuation of tumors and indicate potential therapeutic avenues.
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PMID:MicroRNA-mediated posttranscriptional mechanisms of gene expression in proliferating and quiescent cancer cells. 2269 54

Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate to form orthophosphate. Pyrophosphate can substitute for ATP under certain circumstances. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer, and PPase was identified as a potential gastric tumor-specific marker; it was therefore selected for further study. Clinicopathological analysis, using proteomic analysis and immunohistochemistry, was used to validate PPase as a prognostic marker in gastric cancers. Proteomic analysis showed that PPase was overexpressed in patients with lymph node (LN) metastases and high tumor node metastasis (TNM) stages (p < 0.05). Based on immunohistochemistry, patients whose tumors overexpressed PPase had higher T stages, LN metastasis, a higher TNM stage, a higher cancer recurrence rate, and shorter survival times than patients whose tumors exhibited PPase underexpression (p < 0.05). Gain-of-function and loss-of-function approaches were employed to examine the malignant phenotypes of PPase-overexpressing or PPase-depleted cells. A decrease in PPase expression caused a significant decrease in gastric cancer cell migration and invasion in vitro, whereas forced overexpression of PPase enhanced migration but not invasion. Our findings indicate that PPase is involved in gastric tumor progression and that PPase may be a useful marker for poor prognosis of human gastric cancers.
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PMID:Pyrophosphatase overexpression is associated with cell migration, invasion, and poor prognosis in gastric cancer. 2279 19

Tumor dormancy is a poorly understood phenomenon conceptualized as a protracted quiescent state during which cancer cells are present but clinical disease is not apparent, a condition referred to as "cancer without disease" by Folkman. Examples include the incidental detection of occult in situ tumors in post-mortem organ analysis and cancer recurrence after long disease-free periods. Lack of angiogenic competency has been proposed as a major determinant of the fate of dormant tumors. Other proposed processes include establishment of homeostatic equilibrium between tumor cells and the host's immune system response and a non-permissive microenvironment for tumor growth. Recent cellular and molecular studies suggest that neuroendocrine mediators regulate the biology of tumor progression and act as endogenous modulators of angiogenesis, inflammation, and other molecular processes involved in tumor reactivation from dormancy. We review experimental and clinical evidence and propose that neuroendocrine dynamics of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis might contribute to the loss of tumor dormancy.
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PMID:Tumor dormancy and the neuroendocrine system: an undisclosed connection? 2309 Feb 59

The initiation and progression of pancreatic ductal adenocarcinoma (PDAC) is governed by a series of genetic and epigenetic changes, but it is still unknown whether these alterations are required for the maintenance of primary and metastatic PDAC. We show here that the c-Myc oncogene is upregulated throughout the entire process of neoplastic progression in human PDAC and in genetically engineered mice that express mutant Kras. To experimentally address whether c-Myc is essential for the growth and survival of cancer cells, we developed a novel mouse model that allows a temporally and spatially controlled expression of this oncogene in pancreatic progenitors and derived lineages of the exocrine pancreas. Unlike previous reports, upregulation of c-Myc was sufficient to induce the formation of adenocarcinomas after a short latency without additional genetic manipulation of cell survival pathways. Deficiency in Cdkn2a increased the rate of metastasis but had no effect on tumor latency or c-Myc-mediated cancer maintenance. Despite a macroscopically complete regression of primary, metastatic, and transplantable tumors following the ablation of c-Myc, some cancer cells remained dormant. A significant number of these residual neoplastic cells expressed cancer stem cell markers, and re-expression of exogenous c-Myc in these cells led to rapid cancer recurrence. Collectively, the results of this study suggest that c-Myc plays a significant role in the progression and maintenance of PDAC, but besides targeting this oncogene or its downstream effectors, additional therapeutic strategies are necessary to eradicate residual cancer cells to prevent disease recurrence.
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PMID:Dormant cancer cells contribute to residual disease in a model of reversible pancreatic cancer. 2346 12


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