CMTM Family and Gastrointestinal Tract Cancers: A Comprehensive Review.
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ABSTRACT:
SUBMITTER: Li J
PROVIDER: S-EPMC9056025 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Upper gastrointestinal tract malignancies are among the most challenging cancers with regard to response to treatment and prognosis. Cancers of the esophagus, stomach, pancreas, liver, and biliary tree have dismal 5-year survival, and very modest improvements in this rate have been made in recent times. Oncolytic viruses are being developed to address these malignancies, with a focus on high safety profiles and low off-target toxicities. Each viral platform has evolved to enhance oncolytic potency and the clinical response to either single-agent viral therapy or combined viral treatment with radiotherapy and chemotherapy. A panel of genomic alterations, chimeric proteins, and pseudotyped capsids are the breakthroughs for vector success. This article revisits developments for each viral platform to each tumor type, in an attempt to achieve maximum tumor selectivity. From the bench to clinical trials, the scope of this review is to highlight the beginnings of translational oncolytic virotherapy research in upper gastrointestinal tract malignancies and provide a bioengineering perspective of the most promising platforms.
| S-EPMC5870634 | biostudies-literature
Project description:BackgroundMetastasis is the most frequent type of recurrence in gastrointestinal (GI) cancers, and there is an emerging potential for new diagnostic and therapeutic approaches, especially in the cases of metastatic GI carcinomas. The expression profiles of circulating exosomal microRNAs are of particular interest as novel non-invasive diagnostic and prognostic biomarkers for improved detection of GI cancers in body fluids, especially in the serum of patients with recurrent cancers. The aim of this study is to systematically review primary studies and identify the miRNA profiles of serum exosomes of GI cancers.Methods and designThis systematic review will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidance. Relevant studies will be identified through a comprehensive search of the following main electronic databases: PubMed, Web of Science, Embase, Scopus, and Google Scholar, with no language restrictions (up to July 2017). Full copies of articles will be identified by a defined search strategy and will be considered for inclusion against pre-defined criteria. The quality assessment of the included studies will be performed by the Newcastle-Ottawa Scale (NOS). Data will be analyzed using Stata software V.12. Publication bias will be assessed by funnel plots, Beggs' and Eggers' tests. The levels of evidence for primary outcomes will be evaluated using the GRADE criteria.DiscussionThe analysis of circulating exosomal miRNA profiles provides attractive screening and non-invasive diagnostic tools for the majority of solid tumors including GI cancers. There is limited information regarding the relationship between serum exosomal miRNA profiles and the pathological condition of patients with different GI cancers. Since there is no specific biomarker for GI cancers, we aim to suggest a number of circulating exosomal miRNA candidates as potential multifaceted GI cancer biomarkers for clinical utility.Systematic review registrationPROSPERO CRD42017057129.
| S-EPMC5693515 | biostudies-literature
Project description:Accumulating evidence suggests that Interleukin-33 (IL-33), a member of the IL-1 family, has crucial roles in tissue homeostasis and repair, type 2 immunity, inflammation, and viral infection. IL-33 is a novel contributing factor in tumorigenesis and plays a critical role in regulating angiogenesis and cancer progression in a variety of human cancers. The partially unraveled role of IL-33/ST2 signaling in gastrointestinal tract cancers is being investigated through the analysis of patients' samples and by studies in murine and rat models. In this review, we discuss the basic biology and mechanisms of release of the IL-33 protein and its involvement in gastrointestinal cancer onset and progression.
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Project description:BackgroundCancers of the gastrointestinal (GI) tract are the common leading cause of cancer-related death in the world. Recent advances in cancer therapies such as intensive multidrug chemotherapy and molecular targeted treatment have improved therapeutic efficacy; however, the outcomes are not satisfied. Moreover, these therapies also cause severe side effects. New type of cancer therapies is urgently needed to improve the outcomes and to reduce side effects of GI tract cancers.SummaryThis account is a comprehensive review article on the newly developed, photochemistry-based cancer therapy named as near-infrared photoimmunotherapy (NIR-PIT). NIR-PIT is a highly selective tumor treatment that employs an antibody-photoabsorber conjugate, which is activated by near-infrared light. A world-wide phase 3 clinical trial of NIR-PIT against recurrent head and neck cancer patients is currently underway. NIR-PIT differs from conventional cancer therapies such as surgery, chemotherapy, and radiation in its selectivity for killing cancer cells and cells treated with NIR-PIT leading to immunogenic cell death. Preclinical research in animals with combining cancer-targeting NIR-PIT and other cancer immunotherapies could lead to responses not only in local tumor but also in distant metastases. NIR-PIT also leads to an immediate and dramatic increase in vascular permeability after therapy. From these aspects, NIR-PIT appears to be a promising new form of cancer therapy. NIR-PIT could be readily translated into clinical use for virtually any cancers in the near future provided suitable humanized antibodies are available. Here, we describe the specific advantages and applications of NIR-PIT in the GI tract. Key Messages: We believe that NIR-PIT with NIR excitation light, which can be delivered via a fiber optic diffuser through endoscopes, is a promising method for a new treatment of GI cancers.
| S-EPMC8200364 | biostudies-literature
Project description:ImportanceClonal hematopoiesis (CH) has been associated with development of atherosclerosis and leukemia and worse survival among patients with cancer; however, the association with cancer therapy efficacy, in particular immune checkpoint blockade (ICB), and toxicity has not yet been established. Given the widespread use of ICB and the critical role hematopoietic stem cell-derived lymphocytes play in mediating antitumor responses, CH may be associated with therapeutic efficacy and hematologic toxicity.ObjectiveTo determine the association between CH and outcomes, hematologic toxicity, and therapeutic efficacy in patients with metastatic gastrointestinal tract cancers being treated with systemic therapy, both in the first-line metastatic treatment setting and in ICB.Design, setting, and participantsThis retrospective cohort study included 633 patients with stage IV colorectal (CRC) and esophagogastric (EGC) cancer who were treated with first-line chemotherapy and/or ICB at Memorial Sloan Kettering Cancer Center. Patients underwent matched tumor and peripheral blood DNA sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets next-generation sequencing assay between January 1, 2006, and December 31, 2020.ExposuresClonal hematopoiesis-related genetic alterations were identified by next-generation sequencing of patients' tumor and normal blood buffy coat samples, with a subset of these CH alterations annotated as likely putative drivers (CH-PD) based upon previously established criteria.Main outcomes and measuresPatients with CH and CH-PD in peripheral blood samples were identified, and these findings were correlated with survival outcomes (progression-free survival [PFS] and overall survival [OS]) during first-line chemotherapy and ICB, as well as baseline white blood cell levels and the need for granulocyte colony-stimulating factor (G-CSF) support.ResultsAmong the 633 patients included in the study (390 men [61.6%]; median age, 58 [IQR, 48-66] years), the median age was 52 (IQR, 45-63) years in the CRC group and 61 (IQR, 53-69) years in the EGC group. In the CRC group, 161 of 301 patients (53.5%) were men, compared with 229 of 332 patients (69.0%) in the EGC group. Overall, 62 patients (9.8%) were Asian, 45 (7.1%) were Black or African American, 482 (76.1%) were White, and 44 (7.0%) were of unknown race or ethnicity. Presence of CH was identified in 115 patients with EGC (34.6%) and 83 with CRC (27.6%), with approximately half of these patients harboring CH-PD (CRC group, 44 of 83 [53.0%]; EGC group, 55 of 115 [47.8%]). Patients with EGC and CH-PD exhibited a significantly worse median OS of 16.0 (95% CI, 11.6-22.3) months compared with 21.6 (95% CI, 19.6-24.3) months for those without CH-PD (P = .01). For patients with CRC and EGC, CH and CH-PD were not associated with PFS differences in patients undergoing ICB or first-line chemotherapy. Neither CH nor CH-PD were correlated with baseline leukocyte levels or increased need for G-CSF support.Conclusions and relevanceThese findings suggest CH and CH-PD are not directly associated with the treatment course of patients with metastatic gastrointestinal tract cancer receiving cancer-directed therapy.
| S-EPMC9896303 | biostudies-literature
Project description:BackgroundLaser Tissue Soldering (LTS) is a promising tissue bonding technique in which a solder is applied between the tissues and then irradiated by laser, causing it to solidify and form links with the tissue.MethodsA comprehensive systematic review summarizing the state of research of LTS in the gastrointestinal tract.ResultsMost studies were conducted on large animal tissues, using liquid proteinaceous solder, and irradiated by a continuous wave laser at 808 nm. LTS can provide better sealing and burst pressure than conventional methods. The application of LTS on top of or in addition to sutures showed an impressive increase in burst pressures. LTS may decrease the inflammatory and foreign body reaction caused by sutures.ConclusionsLTS has strong potential to be applied in a clinical setting in leak prevention and in closure of gastrointestinal structures as an adjunct or additional anastomotic technology, decreasing leak rates, morbidity, and mortality.
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Project description:Introduction: Alcohol is a carcinogen for human cancer. This contribution summarizes the relationships between alcohol use and gastrointestinal cancers, and implications for prevention. Methods: Comparative risk assessment and narrative literature review. Results: The following gastrointestinal cancer sites were found to be causally impacted by alcohol use: lip and oral cavity, pharynx other than nasopharynx, esophagus, colon and rectum, and liver. Globally, 368,000 deaths (304,000 men and 64,000 women) and more than 10 million disability-adjusted life years (DALYs) lost (10.1 million; 8.4 million men and 1.6 million women) in 2016 were attributable to alcohol use, making up about 10% of all deaths and DALYs lost due to these cancers, respectively. There are effective and cost-effective alcohol control policies available to reduce this burden, namely the best buys of increasing taxation, reducing availability, and banning advertisement. In addition, public knowledge about the alcohol-cancer link should be increased. Discussion: There are a number of assumptions underlying these estimates, but overall all of them seem to be conservative.
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Project description:Aristolochic acids (AAs) are potent mutagens commonly found in herbal plant-based remedies widely used throughout Asian countries. To understand whether AA is involved in the tumorigenesis of the oro-gastrointestinal tract, we used whole-exome sequencing to profile 54 cases of four distinct types of oro-gastrointestinal tract cancer (OGITC) from Taiwan. A diverse landscape of mutational signatures including those from DNA mismatch repair and reactive oxygen species was observed. APOBEC mutational signatures were observed in 60% of oral squamous cell carcinomas. Only one sample harbored AA mutational signatures, contradictory to prior reports of cancers from Taiwan. The metabolism of AA in the liver and urinary tract, transient exposure time, and high cell turnover rates at OGITC sites may explain our findings. AA signatures in OGITCs are rare and unlikely to be a major contributing factor in oro-gastrointestinal tract tumorigenesis.
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Project description:The oncogenic potential of viral infections is well established and documented for many years already. However, the contribution of (commensal) bacteria and parasites to the development and progression of cancers has only recently gained momentum, resulting in a rapid growth of publications on the topic. Indeed, various bacteria and parasites have been suggested to play a role in the development of gastrointestinal cancer in particular. Therefore, an overview of the current epidemiological knowledge on the association between infections with bacteria and parasites and cancers of the gastrointestinal tract is needed. In this review, we summarized the methodological characteristics and main results of epidemiological studies investigating the association of 10 different bacteria (Bacteroides fragilis, Campylobacter spp., Clostridium spp., Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Porphyromonas gingivalis, non-typhoidal Salmonella, Salmonella Typhi, and Streptococcus spp.) and three parasites (Cryptosporidium spp., Schistosoma spp., and Strongyloides stercoralis) with gastrointestinal cancer. While the large body of studies based on microbiome sequencing provides valuable insights into the relative abundance of different bacterial taxa in cancer patients as compared to individuals with pre-malignant conditions or healthy controls, more research is needed to fulfill Koch's postulates, possibly making use of follow-up data, to assess the complex role of bacterial and parasitic infections in cancer epidemiology. Studies incorporating follow-up time between detection of the bacterium or parasite and cancer diagnosis remain valuable as these allow for estimation of cause-effect relationships.
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Project description:Biliary tract cancers have dismal prognoses even when cytotoxic chemotherapy is administered. There is an unmet need to develop precision treatment approaches using comprehensive genomic profiling. A total of 121 patients with biliary tract cancers were analyzed for circulating-tumor DNA (ctDNA) and/or tissue-based tumor DNA (tissue-DNA) using clinical-grade next-generation sequencing: 71 patients (59%) had ctDNA; 90 (74%), tissue-DNA; and 40 (33%), both. Efficacy of targeted therapeutic approaches was assessed based upon ctDNA and tissue-DNA. At least one characterized alteration was detected in 76% of patients (54/71) for ctDNA [median, 2 (range, 0-9)] and 100% (90/90) for tissue-DNA [median, 4 (range, 1-9)]. Most common alterations occurred in TP53 (38%), KRAS (28%), and PIK3CA (14%) for ctDNA vs TP53 (44%), CDKN2A/B (33%) and KRAS (29%) for tissue-DNA. In 40 patients who had both ctDNA and tissue-DNA sequencing, overall concordance was higher between ctDNA and metastatic site tissue-DNA than between ctDNA and primary tumor DNA (78% vs 65% for TP53, 100% vs 74% for KRAS and 100% vs 87% for PIK3CA [But not statistical significance]). Among 80 patients who received systemic treatment, the molecularly matched therapeutic regimens based on genomic profiling showed a significantly longer progression-free survival (hazard ratio [95%confidence interval], 0.60 [0.37-0.99]. P = .047 [multivariate]) and higher disease control rate (61% vs 35%, P = .04) than unmatched regimens. Evaluation of ctDNA and tissue-DNA is feasible in biliary tract cancers.
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