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Current Oncology (Toronto, Ont.) May 2023Colorectal cancer is the most prevalent gastrointestinal neoplasm. When metastatic, the disease has limited systemic treatment options. Novel targeted therapies have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Colorectal cancer is the most prevalent gastrointestinal neoplasm. When metastatic, the disease has limited systemic treatment options. Novel targeted therapies have expanded these options for subsets with specific molecular alterations, such as microsatellite instability (MSI)-high cancers, but additional treatments and combinations are in urgent need to improve outcomes and improve survival of this incurable disease. The fluoropyrimidine-derivative trifluridine, in combination with tipiracil, has been introduced as a third-line treatment, and more recently, it was studied in combination with bevacizumab. This meta-analysis reports on studies with this combination in clinical practice outside clinical trials.
METHODS
A literature search in the Medline/PubMed and Embase databases was executed for finding series of trifluridine/tipiracil with bevacizumab in metastatic colorectal cancer. Criteria for inclusion in the meta-analysis were English or French language of the report, inclusion of twenty or more patients with metastatic colorectal cancer treated with trifluridine/tipiracil in combination with bevacizumab outside of a trial and containing information regarding response rates, progression-free survival (PFS), and overall survival (OS). Information on the demographics of the patients and on adverse effects of treatment was also collected.
RESULTS
Eight series with a total of 437 patients were eligible for the meta-analysis. The performed meta-analysis discovered a summary response rate (RR) of 2.71% (95% confidence interval (CI): 1.11-4.32%) and a disease control rate (DCR) of 59.63% (95% CI: 52.06-67.21%). Summary PFS was 4.56 months (95% CI: 3.57-5.55 months), and summary OS was 11.17 months (95% CI: 10.15-12.19 months). Common adverse effects identified mirrored the adverse-effect profile of the two components of the combination.
CONCLUSION
The current systematic review and meta-analysis reports the efficacy of trifluridine/tipiracil with bevacizumab in advanced lines of therapy for metastatic colorectal cancer in the setting of clinical practice outside clinical trials. Discovery of predictive biomarkers of response to trifluridine/tipiracil with bevacizumab will promote the tailoring of this treatment to individual patients to maximize clinical benefit.
Topics: Humans; Bevacizumab; Uracil; Colorectal Neoplasms; Trifluridine; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Rectal Neoplasms
PubMed: 37366880
DOI: 10.3390/curroncol30060397 -
Seminars in Cancer Biology Sep 2022Radiological imaging is an integral component of cancer care, including diagnosis, staging, and treatment response monitoring. It contains rich information about tumor... (Review)
Review
Radiological imaging is an integral component of cancer care, including diagnosis, staging, and treatment response monitoring. It contains rich information about tumor phenotypes that are governed not only by cancer cellintrinsic biological processes but also by the tumor microenvironment, such as the composition and function of tumor-infiltrating immune cells. By analyzing the radiological scans using a quantitative radiomics approach, robust relations between specific imaging and molecular phenotypes can be established. Indeed, a number of studies have demonstrated the feasibility of radiogenomics for predicting intrinsic molecular subtypes and gene expression signatures in breast cancer based on MRI. In parallel, promising results have been shown for inferring the amount of tumor-infiltrating lymphocytes, a key factor for the efficacy of cancer immunotherapy, from standard-of-care radiological images. Compared with the biopsy-based approach, radiogenomics offers a unique avenue to profile the molecular makeup of the tumor and immune microenvironment as well as its evolution in a noninvasive and holistic manner through longitudinal imaging scans. Here, we provide a systematic review of the state of the art radiogenomics studies in the era of immunotherapy and discuss emerging paradigms and opportunities in AI and deep learning approaches. These technical advances are expected to transform the radiogenomics field, leading to the discovery of reliable imaging biomarkers. This will pave the way for their clinical translation to guide precision cancer therapy.
Topics: Biomarkers, Tumor; Breast Neoplasms; Female; Genomics; Humans; Immunotherapy; Lymphocytes, Tumor-Infiltrating; Tumor Microenvironment
PubMed: 33290844
DOI: 10.1016/j.semcancer.2020.12.005 -
Therapeutic Advances in Medical Oncology 2023Gastroenteropancreatic (GEP) neuroendocrine neoplasms with Ki-67 > 20% were subdivided in the most recent 2019 World Health Organization histopathological... (Review)
Review
BACKGROUND
Gastroenteropancreatic (GEP) neuroendocrine neoplasms with Ki-67 > 20% were subdivided in the most recent 2019 World Health Organization histopathological classification into grade 3 (G3) neuroendocrine tumors (NETs), described as well-differentiated tumors, and neuroendocrine carcinomas, which are described as poorly differentiated tumors. This classification met the demand noted for different prognoses between these subgroups, prompting the need for treatment recommendations for well-differentiated G3 tumors.
METHODS
We systematically searched medical literature databases and oncology conferences for studies on G3 GEP NET to describe epidemiology, diagnosis, molecular features, and treatments used. We excluded studies that did not discriminate G3 NET data. Data were tabulated and described, and a quality analysis of the reports was performed.
RESULTS
We found 23 published studies and six abstracts; 89.7% of studies were retrospective, six were composed exclusively of G3 NETs. Among 761 patients, the median number of patients per study was 15, most were male and older than 60 years, and functional imaging tests were positive in more than 80% of cases. Overall, the scientific evidence supporting the treatment of G3 GEP NETs is limited. For localized disease, resection remains the standard treatment but there is no evidence to support neoadjuvant or adjuvant therapy. For advanced disease, capecitabine and temozolomide seems to be the most effective option, with a response rate, median progression-free survival, and median overall survival up to 37.9%, 20.6 months, and 41.2 months, respectively.
CONCLUSION
The latest available data on the epidemiology, diagnosis, molecular changes, and treatment of G3 GEP NET are described. Yet, the level of evidence for treatment recommendations is low, as most studies are retrospective. A treatment algorithm for G3 GEP NET is proposed.
PubMed: 36950274
DOI: 10.1177/17588359231156218 -
American Journal of Blood Research Dec 2013Granulocytic sarcoma also called myeloid sarcoma is an extramedullary tumor of immature granulocytic cells. It is a rare entity, and mostly accompanied by acute myeloid... (Review)
Review
Granulocytic sarcoma also called myeloid sarcoma is an extramedullary tumor of immature granulocytic cells. It is a rare entity, and mostly accompanied by acute myeloid leukemia. It is observed during the course of myeloproliferative disorders especially in chronic myeloid leukemia and myelodysplastic syndromes. In some rare circumstances, it is detected before clinical signs of leukemia or other diseases. When the bone marrow biopsy reveals no other hematologic malignancies, the granulocytic sarcoma is described as nonleukemic, primary or isolated. It is observed at any part of the body but the most common locations are soft tissues, bone, peritoneum and lymph nodes. Presenting signs or symptoms are mainly due to mass effect of the tumor and dysfunction of the organ, or the tissue that is affected. The diagnosis is performed by biopsy of the tumor. The tumor consists of immature granulocytic cells, which could be documented by H&E, immunohistochemistry, and flow cytometric methods. Fluorescence in-situ hybridization and molecular analysis are also performed. The optimal time and type of treatment is not clear. Surgery could be an option especially for tumors, which cause organ dysfunction and/or obstruction. Systemic treatment should be considered in all patients because without systemic treatment, relapses and progression to acute myeloid leukemia is the ultimate fate of the disease in many cases. Cytarabine-containing remission-induction chemotherapies have been the most applied therapeutic strategies, but it is not clear whether the consolidation therapies are required or not, and what kind of regimens are appropriate. The role of hematopoietic stem cell transplantation (HSC) as a consolidation regimen is not clear, but, after the relapse of the disease with or without bone marrow involvement, HSC transplantation should be considered in suitable patients after the reinduction performed by AML chemotherapies. There is only limited data about the role of radiotherapy in these patients. It could be used in patients with relapsed disease, organ dysfunction which should be quickly relieved and inadequate response to chemotherapy. The effect of radiotherapy on overall survival is not known. New prospective studies and clinical trials are needed to generate guidelines for the treatment of primary granulocytic sarcomas.
PubMed: 24396704
DOI: No ID Found -
Journal of Immunology (Baltimore, Md. :... May 2023The mammalian heart is characterized by the presence of striated myocytes, which allow continuous rhythmic contraction from early embryonic development until the last...
The mammalian heart is characterized by the presence of striated myocytes, which allow continuous rhythmic contraction from early embryonic development until the last moments of life. However, the myocardium contains a significant contingent of leukocytes from every major class. This leukocyte pool includes both resident and nonresident immune cells. Over recent decades, it has become increasingly apparent that the heart is intimately sensitive to immune signaling and that myocardial leukocytes exhibit an array of critical functions, both in homeostasis and in the context of cardiac adaptation to injury. Here, we systematically review current knowledge of all major leukocyte classes in the heart, discussing their functions in health and disease. We also highlight the connection between the myocardium, immune cells, lymphoid organs, and both local and systemic immune responses.
Topics: Animals; Myocytes, Cardiac; Myocardium; Leukocytes; Signal Transduction; Mammals
PubMed: 37068299
DOI: 10.4049/jimmunol.2200924 -
Clinical and Molecular Hepatology Apr 2023Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide and is characterized by complex molecular carcinogenesis. Neuropilins (NRPs) NRP1... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide and is characterized by complex molecular carcinogenesis. Neuropilins (NRPs) NRP1 and NRP2 are the receptors of multiple proteins involved in key signaling pathways associated with tumor progression. We aimed to systematically review all the available findings on their role in HCC. We searched the Scopus, Web of Science (WOS), PubMed, Cochrane and Embase databases for articles evaluating NRPs in preclinical or clinical HCC models. This study was registered in PROSPERO (CRD42022349774) and include 49 studies. Multiple cellular and molecular processes have been associated with one or both NRPs, indicating that they are potential diagnostic and prognostic biomarkers in HCC patients. Mainly NRP1 has been shown to promote tumor cell survival and progression by modulating several signaling pathways. NRPs mainly regulate angiogenesis, invasion and migration and have shown to induce invasion and metastasis. They also regulate the immune response and tumor microenvironment, showing a crucial interplay with the hypoxia response and microRNAs in HCC. Altogether, NRP1 and NRP2 are potential biomarkers and therapeutic targets, providing novel insight into the clinical landscape of HCC patients.
Topics: Humans; Carcinoma, Hepatocellular; Neuropilins; Liver Neoplasms; Signal Transduction; Biomarkers; Biomarkers, Tumor; Tumor Microenvironment
PubMed: 36726054
DOI: 10.3350/cmh.2022.0425 -
Hormone Research in Paediatrics 2011The human glucocorticoid receptor (hGR) is a ubiquitously expressed intracellular, ligand-dependent transcription factor, which mediates the action of glucocorticoids... (Review)
Review
CONTEXT
The human glucocorticoid receptor (hGR) is a ubiquitously expressed intracellular, ligand-dependent transcription factor, which mediates the action of glucocorticoids and influences physiological functions essential for life. Alterations in the molecular mechanisms of hGR action impair glucocorticoid signal transduction and alter tissue sensitivity to glucocorticoids. This review summarizes the pathophysiology, molecular mechanisms and clinical aspects of primary generalized glucocorticoid resistance (PGGR) and hypersensitivity (PGGH).
EVIDENCE ACQUISITION
A systematic review of the published, peer-reviewed medical literature (PubMed: 1975 through May 2011) was conducted to identify original articles and reviews on this topic.
EVIDENCE SYNTHESIS
Evidence synthesis was relied upon the experience of a number of experts in the field, including our extensive personal experience.
CONCLUSIONS
The molecular basis of PGGR and PGGH has been ascribed to mutations in the hGR gene, which alter tissue sensitivity to glucocorticoids. The stochastic nature of glucocorticoid signaling pathways in association with the variable effect that hGR gene mutations/polymorphisms might have on glucocorticoid signal transduction indicates that alterations in hGR action may have important implications for many critical biological processes, such as the behavioral and physiological responses to stress, the immune and inflammatory reaction, as well as growth and reproduction.
Topics: Diagnostic Techniques, Endocrine; Drug Hypersensitivity; Drug Resistance; Genetic Diseases, Inborn; Glucocorticoids; Humans; Models, Biological; Mutation; Receptors, Glucocorticoid
PubMed: 21912096
DOI: 10.1159/000330759 -
Military Medical Research Oct 2023Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,...
BACKGROUND
Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment.
METHODS
To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student's t-test followed by pathway analysis and comparison between the different omics modalities.
RESULTS
Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection.
CONCLUSION
This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.
Topics: Humans; Multiomics; Exercise; Cytokines
PubMed: 37853489
DOI: 10.1186/s40779-023-00477-5 -
Biochemical Society Transactions Jun 2021Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant to...
Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant to radiation. The biological response to radiobiological hypoxia is one of few physiologically relevant stresses that activates both the unfolded protein and DNA damage responses (UPR and DDR). Links between these pathways have been identified in studies carried out in normoxia. Based in part on these previous studies and recent work from our laboratory, we hypothesised that the biological response to hypoxia likely includes overlap between the DDR and UPR. While inhibition of the DDR is a recognised strategy for improving radiation response, the possibility of achieving this through targeting the UPR has not been realised. We carried out a systematic review to identify links between the DDR and UPR, in human cell lines exposed to <2% O2. Following PRISMA guidance, literature from January 2010 to October 2020 were retrieved via Ovid MEDLINE and evaluated. A total of 202 studies were included. LAMP3, ULK1, TRIB3, CHOP, NOXA, NORAD, SIAH1/2, DYRK2, HIPK2, CREB, NUPR1, JMJD2B, NRF2, GSK-3B, GADD45a, GADD45b, STAU1, C-SRC, HK2, CAV1, CypB, CLU, IGFBP-3 and SP1 were highlighted as potential links between the hypoxic DDR and UPR. Overall, we identified very few studies which demonstrate a molecular link between the DDR and UPR in hypoxia, however, it is clear that many of the molecules highlighted warrant further investigation under radiobiological hypoxia as these may include novel therapeutic targets to improve radiotherapy response.
Topics: Animals; Apoptosis; Cell Line, Tumor; DNA Damage; Humans; Hypoxia; Neoplasms; Protein Serine-Threonine Kinases; Signal Transduction; Unfolded Protein Response
PubMed: 34003246
DOI: 10.1042/BST20200861 -
Cureus Nov 2022Breast cancer is the most common type of cancer in women besides basal cell and squamous cell skin cancer. The current systemic therapy guidelines for this heterogeneous... (Review)
Review
Breast cancer is the most common type of cancer in women besides basal cell and squamous cell skin cancer. The current systemic therapy guidelines for this heterogeneous disease are mainly based on the molecular subtypes. However, more research is required to improve rates of therapy resistance and prevent side effects. Previous studies have shown that the human gut microbiota may have an important role in carcinogenesis as well as therapy outcomes, but this factor has not yet been integrated into therapy protocols. This systematic review aims to analyze how response rates and side effect profiles of breast cancer systemic therapies may be affected by the gastrointestinal microbiota. A literature search was performed using multiple databases and keywords related to gastrointestinal microbiota, breast cancer, and anticancer drugs. Studies were excluded if they primarily focused on diseases other than breast cancer. Abstracts, reviews, meta-analyses, and animal experiments were also excluded. After screening, nine studies met all selection criteria and included a total of 566 participants. Most studies described the impact of the gut microbiota on therapy response, but a few additionally discussed chemotherapy side effects, probiotics, or antibiotics. In general, diversity and specific microbiota were linked to chemotherapy response as well as prognosis. Microbiota diversity was also predictive of side effects such as neurological symptoms, weight gain, and constipation. The diversity and composition of gastrointestinal microbiota may serve as biomarkers and provide pathways for the optimization of chemotherapy in breast cancer patients.
PubMed: 36540440
DOI: 10.7759/cureus.31648