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Prediction of cancer drugs by chemical-chemical interactions.

Cancer, which is a leading cause of death worldwide, places a big burden on health-care system. In this study, an order-prediction model was built to predict a series of cancer drug indications based on chemical-chemical interactions. According to the confidence scores of their interactions, the order from the most likely cancer to the least one was obtained for each query drug. The 1(st) order prediction accuracy of the training dataset was 55.93%, evaluated by Jackknife test, while it was 55.56% and 59.09% on a validation test dataset and an independent test dataset, respectively. The propos

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… Floxuridine-Cancers of the digestive system Floxuridine (D04197) is used to treat hepatic metastases of gastrointestinal adenocarcinomas, and also used for palliation of cancers in the liver and gastrointestinal tract [58] . … Moreover, hepatic arterial infusion (HAI) can significantly enhance the antitumor activity of floxuridine against colorectal liver metastases, as compared with systemic infusion [59] . …

Intrathecal administration of Y-27632, a specific rho-associated kinase inhibitor, for rat neoplastic meningitis.

The small GTP-binding protein Rho and its target Rho-associated kinase trigger an intracellular signaling cascade that controls actin cytoskeleton and plays an essential role in cell motility and adhesion. A specific Rho-associated kinase inhibitor, Y-27632, has been reported to inhibit cancer invasion. Clinically, disseminated tumor cells in the cerebrospinal fluid invade the intraparenchymal region, damaging the brain and nerves, resulting in fatal brain stem dysfunction, despite intrathecal chemotherapy. To expand therapeutic options for this devastating neoplastic meningitis, we evaluated

Malnutrition and cachexia in ovarian cancer patients: pathophysiology and management.

In ovarian cancer patients the poor nutritional status and cachexia are caused by the metabolic effects of the enlarging tumor masses and bowel obstruction. These patients may have a high resting energy expenditure due to increase in Cori cycle activity, glucose and triglyceride-fatty acid cycling and gluconeogenesis. Biochemical mediators of cachexia include cytokines, such as tumor necrosis factor and interleukin-6, and tumor-produced catabolic factors, such as lipid-mobilizing factor, proteolysis-inducing factor, and anemia-inducing factor. Mechanisms involved in the pathogenesis of obstruc

Current and Emerging Therapeutic Targets for the Treatment of Cholangiocarcinoma: An Updated Review.

Cholangiocarcinoma is a malignancy of the bile ducts that is often associated with late diagnosis, poor overall survival, and limited treatment options. The standard of care therapy for cholangiocarcinoma has been cytotoxic chemotherapy with modest improvements in overall survival with the addition of immune checkpoint inhibitors. The discovery of actionable mutations has led to the advent of targeted therapies against FGFR and IDH-1, which has expanded the treatment landscape for this patient population. Significant efforts have been made in the pre-clinical space to explore novel immunothera

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… /or metastatic ICC | Cryoablation, sintilimab (anti-PD-1), lenvatinib (VEGFR1-3) | ORR | Enrolling NCT04299581 | II | Unresectable and/or metastatic ICC | Cryoablation and Camrelizumab (Anti-PD-1) | ORR | Enrolling NCT04891289 | II | Unresectable and liver metastasis ICC | Gemcitabine, oxaliplatin, floxuridine … cholangiocarcinoma | 177Lu-EB-FAPI PRRT (FAP inhibitor molecule) | Hematoxicity, ORR, hepatotoxicity, renal toxicity | Enrolling NCT04413734 | II | Unresectable and/or metastatic BTC | triprilumab (anti-PD-1), GemCis | PFS | Enrolling NCT04251715 | IId | Unresectable ICC | mFOLFIRINOX, hepatic arterial infusion of floxuridine …

Review of cancer therapies for the perioperative physician.

Advances in cancer treatments over the past decades combining chemotherapy with novel technologies in immunotherapies, radiation therapies, and interventional radiology have prolonged life expectancy. Patients have more options for treatments of their primary or metastatic diseases. Increased procedural techniques amid an aging population with multiple comorbidities present risks and challenges in the perioperative period.Chemotherapy remains the mainstay of cancer treatment, can be given intraoperatively, and is combined with other treatment modalities. Immunotherapy is particular to cancer c

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… brain tumors | Bone marrow suppression, dose‐dependent risk of leukemia, renal failure, liver failure, cardiomyopathy, pulmonary fibrosis, peripheral neuropathy Antimetabolites | Folic acid antagonist — methotrexate, pemetrexed, praxatrexate Pyrimidine antagonist — 5‐fluorouracil (5‐FU), decitabine, floxuridine …

Ocular complications of antineoplastic therapies.

Ocular complications of antineoplastic agents can have a profound effect on the quality of life of cancer patients. New oncologic treatments like monoclonal antibodies, immunotherapies, antibody-drug conjugates, checkpoint inhibitors and growth factor receptors have resulted in increased ocular complications. These ocular complications differs in respect to distinct mechanisms of actions and lead to significant challenges in the management of cancer patients. In this review, we reviewed literature, clinical studies and cases detailing ocular complications due to administration of antineoplasti

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… Five-minute treatments with fluorouracil, floxuridine, and mitomycin have long-term effects on human Tenon's capsule fibroblasts. Arch. Ophthalmol. 110(8), 1150–1154 (1992). 28. Shapiro MS, Thoft RA, Friend J, Parrish RK, Gressel MG. 5-Fluorouracil toxicity to the ocular surface epithelium. …

The Role of Drug Repurposing in the Development of Novel Antimicrobial Drugs: Non-Antibiotic Pharmacological Agents as Quorum Sensing-Inhibitors.

Background: The emergence of multidrug-resistant organisms (MDROs) is a global public health issue, severely hindering clinicians in administering appropriate antimicrobial therapy. Drug repurposing is a drug development strategy, during which new pharmacological applications are identified for already approved drugs. From the viewpoint of the development of virulence inhibitors, inhibition of quorum sensing (QS) is a promising route because various important features in bacterial physiology and virulence are mediated by QS-dependent gene expression. Methods: Forty-five pharmacological agents,

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… The FDA-approved anti-cancer drugs, streptozotocin and floxuridine, reduce the virulence of Staphylococcus aureus Sci. Rep. 2018 8 1 10 10.1038/s41598-018-20617-5 29410445 PMC5802796 104. Abbas H.A. Shaldam M.A. …

Chemotherapy Side-Effects: Not All DNA Damage Is Equal.

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark

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… Methotrexate therapy often leads to liver cirrhosis and fibrosis, and capecitabine, gemcitabine, and floxuridine frequently cause hepatitis and cholestasis [ 38 , 39 , 43 ]. 2.2.3. …

Интеграция нанотехнологий в онкологию для передовых стратегий наночастиц в целевую диагностику и лечение рака.

Рак остается одной из основных глобальных проблем в области здравоохранения. Обычная терапия часто ограничивается низкой избирательностью опухолей, системной токсичностью, резистентностью к многочисленным лекарствам и неоптимальными фармакокинетиками. Нанотехнология предлагает преобразующий подход в онкологии. Она позволяет осуществлять целенаправленные поставки наркотиков, контролировать или стимулировать их высвобождение и использовать многофункциональные платформы, сочетающие в себе терапию и диагностику. Нанопчасти повышают растворимость наркотиков, продлевают циркуляцию и повышают внутрик

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… III, Completed (2014) NCT02181075 , Phase I, Completed (2014) NCT02536183 , Phase I, Terminated (2016) NCT02850419 , Phase II, Withdrawn (2017) NCT03749850 , Phase I, Unknown status (2021) NCT04791228 , Phase II, Withdrawn (2021) NCT04852367 , Phase I, Withdrawn (2021) CPX-1 Liposomal irinotecan and floxuridine … Completed (2014) | | | NCT02536183 , Phase I, Terminated (2016) | | | NCT02850419 , Phase II, Withdrawn (2017) | | | NCT03749850 , Phase I, Unknown status (2021) | | | NCT04791228 , Phase II, Withdrawn (2021) | | | NCT04852367 , Phase I, Withdrawn (2021) CPX-1 | Liposomal irinotecan and floxuridine …

Targeted Hybrid Nanocarriers as Co-Delivery Systems for Enhanced Cancer Therapy.

Hybrid nanocarriers have realized a growing interest in drug delivery research because of the potential of being able to treat, manage or cure diseases that previously had limited therapy or cure. Cancer is currently considered the second leading cause of death globally. This makes cancer therapy a major focus in terms of the need for efficacious and safe drug formulations that can be used to reduce the rate of morbidity and mortality globally. The major challenge encountered over the years with cancer chemotherapy is the non-selectivity of anticancer drugs, leading to severe adverse effects i

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… Inhibit the microtubule disassembly | Breast, lung, myelomas, lymphomas, leukemias Anti-metabolites* | Azacitidine, clofarabine, cytarabine, decitabine, floxuridine, gemcitabine, 5-fluorouracil, 6-mercaptopurine, hydroxyurea, methotrexate, thioguanine, trifluridine/tipiracil combo | Nucleus | Disrupts …

Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances.

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug

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… In a recent study, the drugs, oligo-floxuridine (FdU) and monomethyl auristatine E (MMAE), were chemically coupled to exotoxin A from Pseudomonase aeruginosa and diphtheria toxin from Corynebacterium diphtheria, respectively, to form self-assembled protein NPs with an average size of 50 nm targeting …

What Drives Innovation: The Canadian Touch on Liposomal Therapeutics.

Liposomes are considered one of the most successful drug delivery systems (DDS) given their established utility and success in the clinic. In the past 40⁻50 years, Canadian scientists have made ground-breaking discoveries, many of which were successfully translated to the clinic, leading to the formation of biotech companies, the creation of research tools, such as the Lipex Extruder and the NanoAssemblr™, as well as contributing significantly to the development of pharmaceutical products, such as Abelcet®, MyoCet®, Marqibo®, Vyxeos®, and Onpattro™, which are making positive impacts on patient

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… Tardi et al. illustrated an example of a system in which cholesterol was used to control drug leakage rates and with this system, they were able to maintain a 1:1 synergistic ratio of irinotecan and floxuridine in vivo [ 72 ]. …

Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy.

BackgroundGlucocorticoids are often used in the treatment of nonhematologic malignancy. This review summarizes the clinical evidence of the effect of glucocorticoid therapy on nonhematologic malignancy.MethodsA systematic review of clinical studies of glucocorticoid therapy in patients with nonhematologic malignancy was undertaken. Only studies having endpoints of tumor response or tumor control or survival were included. PubMed, EMBASE, the Cochrane Register/Databases, conference proceedings (ASCO, AACR, ASTRO/ASTR, ESMO, ECCO) and other resources were used. Data was extracted using a standar

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… Ludwig Breast Cancer Study Group Cancer Res 1985 45 4454 4459 2862995 Kemeny N Conti JA Cohen A Campana P Huang Y Shi WJ Botet J Pulliam S Bertino JR Phase II study of hepatic arterial floxuridine, leucovorin, and dexamethasone for unresectable liver metastases from colorectal carcinoma J Clin Oncol …

Non-coding RNA/microRNA-modulatory dietary factors and natural products for improved cancer therapy and prevention: Alkaloids, organosulfur compounds, aliphatic carboxylic acids and water-soluble vitamins.

Non-coding small RNA molecules, the microRNAs (miRNAs), contribute decisively to the epigenetic regulation processes in cancer cells. Problematic pathogenic properties of cancer cells and the response of cancers towards anticancer drugs are highly influenced by miRNAs. Both increased drug activity and formation of tumor resistance are regulated by miRNAs. Further to this, the survival and proliferation of cancer cells and the formation of metastases is based on the modulated expression of certain miRNAs. In particular, drug-resistant cancer stem-like cells (CSCs) depend on the presence and abs

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… Genome-wide mRNA and microRNA profiling of the NCI 60 cell-line screen and comparison of FdUMP[10] with fluorouracil, floxuridine, and topoisomerase 1 poisons Mol. Cancer Ther. 9 2010 3105 3114 21159603 10.1158/1535-7163.MCT-10-0674 PMC3059097 74 Corcoran C. Friel A.M. Duffy M.J. Crown J. …

DNA Damaging Drugs

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Recent Advances in Nanoparticle-Based Co-Delivery Systems for Cancer Therapy.

Cancer therapies have advanced tremendously throughout the last decade, yet multiple factors still hinder the success of the different cancer therapeutics. The traditional therapeutic approach has been proven insufficient and lacking in the suppression of tumor growth. The simultaneous delivery of multiple small-molecule chemotherapeutic drugs and genes improves the effectiveness of each treatment, thus optimizing efficacy and improving synergistic effects. Nanomedicines integrating inorganic, lipid, and polymeric-based nanoparticles have been designed to regulate the spatiotemporal release of

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… The latter also investigated CPX-1, which is the encapsulation of irinotecan and floxuridine, specifically in patients with colorectal cancer [ 71 ]. The administration of CPX-351 and CPX-1 showed a higher remission rate and a prolonged survival rate in patients. …

Critical considerations for targeting colorectal liver metastases with nanotechnology.

Colorectal cancer remains a significant cause of morbidity and mortality worldwide. Half of all patients develop liver metastases, presenting unique challenges for their treatment. The shortcomings of conventional chemotherapy has encouraged the use of nanomedicines; the application of nanotechnology in the diagnosis and treatment of disease. In spite of technological improvements in nanotechnology, the complexity of biological systems hinders the prospect of nanomedicines being applied in cancer therapy at the present time. This review highlights current biological barriers and discusses aspe

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… Jazz Pharmaceuticals, 2019 NK012 (Nippon Kayaku) | Polymeric micelle of SN‐38 (PEG‐PGA), ~20 nm | Small cell lung cancer, metastatic colorectal cancer | Phase II | | Kayaku, 2019 ; Nakajima et al., 2008 ; Takahashi et al., 2010 CPX‐1 (Jazz Pharmaceuticals) | Liposomal formulation of Irinotecan and Floxuridine …

Timeline of Translational Formulation Technologies for Cancer Therapy: Successes, Failures, and Lessons Learned Therefrom.

Over the past few decades, the field of cancer therapy has seen a significant change in the way in which formulations are designed and developed, resulting in more efficient products that allow us to ultimately achieve improved drug bioavailability, efficacy, and safety. However, although many formulations have entered the market, many others have fallen by the wayside leaving the scientific community with several lessons to learn. The successes (and failures) achieved with formulations that have been approved in Europe and/or by the FDA for the three major types of cancer therapy (peptide-bas

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… In 2002, another intra-arterial formulation of microspheres loaded with 90 Y, under the tradename SIR-Spheres ® , was authorized by the FDA and CE-marked as a medical device for the treatment of unresectable metastatic liver tumors from primary colorectal cancer with adjuvant chemotherapy with floxuridine …

Emerging Nanotherapeutic Approaches to Overcome Drug Resistance in Cancers with Update on Clinical Trials.

A key issue with modern cancer treatments is the emergence of resistance to conventional chemotherapy and molecularly targeted medicines. Cancer nanotherapeutics were created in order to overcome the inherent limitations of traditional chemotherapeutics. Over the last few decades, cancer nanotherapeutics provided unparalleled opportunities to understand and overcome drug resistance through clinical assessment of rationally designed nanoparticulate delivery systems. In this context, various design strategies such as passive targeting, active targeting, nano-drug, and multimodal nano-drug combin

Pleuropulmonary Changes Induced by Drugs in Patients with Hematologic Diseases

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… Drugs causing cellular interstitial pneumonia in hematology include azacytidine, azathioprine, chlorambucil, 2-chlorodeoxyadenosine (cladribine), cyclophosphamide, cytarabine, dasatinib, floxuridine, fludarabine, GM-CSF, gemtuzumab, hydroxurea, imatinib, interferon alpha and beta, lenalidomide, methotrexate …