Comparative Toxic and Therapeutic Effects of Adriamycin and Bleomycin in Malignant Lymphoma

The toxic and therapeutic results obtained during phase I and phase II evaluation of adriamycin (ADM) and bleomycin (BLM) in 92 adequately treated cases with malignant lymphomas are reviewed. The number of pretreated patients as well as the different histologic expression of lymphoma are given together with the incidence of toxic manifestations (table 3, text-fig. 1). Stomatitis and alopecia are caused by both drugs and show about the same incidence as first sign of toxicity. Interstitial pulmonary lesions produced by BLM were observed in a fairly large percentage of cases and represent at the dosage used a limiting factor to prolonged administration. The therapeutic response has been evaluated on the Karnofsky's scale. With ADM category I response occurred in 72.2% of cases and with BLM in 50% (table 5, 6). Complete remissions for more than 1 year occurred in 3 patients treated with ADM and 1 with BLM. With both drugs all types of lesions responded, including bone marrow invasion. In responsive patients remissions occurred promptly (average 13.7 days with ADM and 10.3 days with BLM) (table 4). Because of their toxic and therapeutic properties, both drugs appear suitable for therapeutic trials in combination with conventional agents.

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Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary SuccessOK

Biomedicines ◽

10.3390/biomedicines9060667 ◽

2021 ◽

Vol 9 (6) ◽

pp. 667

Author(s):

Gabriella Racchetti ◽

Jacopo Meldolesi

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Immune Responses ◽

Extracellular Vesicles ◽

Immune Regulation ◽

Great Increase ◽

The Body ◽

Cell Aging ◽

Therapeutic Effects ◽

Therapeutic Properties

Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. About two decades ago, these cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Such discovery induced great increase of their investigation. Soon thereafter, however, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation. Here we illustrate the MSC-EV therapeutic effects, largely mediated by specific miRNAs, covering various diseases and pathological processes occurring in the bones, heart and vessels, kidney, and brain. MSC-EVs operate also on the development of cancers and on COVID-19, where they alleviate the organ lesions induced by the virus. Therapy by MSC-EVs can be improved by combination of their innate potential to engineering processes inducing precise targeting and transfer of drugs. The unique properties of MSC-EVs explain their intense studies, carried out with extraordinary success. Although not yet developed to clinical practice, the perspectives for proximal future are encouraging.

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The Treatment of Iron-deficiency Anemia—Palatable but Ineffective Iron Medication

PEDIATRICS ◽

10.1542/peds.31.6.1041 ◽

1963 ◽

Vol 31 (6) ◽

pp. 1041-1044

Author(s):

LOUIS K DIAMOND ◽

J. LAWRENCE NAIMAN ◽

DONALD M. ALLEN ◽

FRANK A. OSKI,

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Ferrous Sulfate ◽

Oral Iron ◽

Gastrointestinal Absorption ◽

Deficiency Anemia ◽

Therapeutic Effects ◽

Rapid Rise ◽

Carbohydrate Complex ◽

Therapeutic Results

Experience with a new oral iron-carbohydrate complex (Jefron) in the treatment of iron-deficiency anemia shows that the therapeutic results are inferior to those obtainable with ferrous sulfate. Many children showed no response after months of treatment with this drug and when subsequently placed on ferrous sulfate therapy showed a rapid rise in hemoglobin to normal levels. Preliminary studies suggest that poor gastrointestinal absorption may be a factor in the inadequate therapeutic effects.

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Comparison of the therapeutic effects of hUC-MSC intravenous delivery and intraperitoneal administration of MSCs encapsulated in alginate capsules for the treatment of rat liver cirrhosis

10.1101/2021.04.26.441497 ◽

2021 ◽

Author(s):

Svitlana Rymar ◽

Polina Pikus ◽

Ianina Pokholenko ◽

Polina Buchek ◽

Nadiya Shuvalova ◽

...

Keyword(s):

Liver Cirrhosis ◽

Umbilical Cord ◽

Therapeutic Potential ◽

Intraperitoneal Administration ◽

Liver Parenchyma ◽

Negative Control ◽

Human Umbilical Cord ◽

Therapeutic Effects ◽

Alginate Capsules ◽

Therapeutic Properties

Mesenchymal stem cells are the most promising regenerative medicine tool for the treatment of various diseases, including liver disease, although the exact mechanism of their therapeutic action remains unclear. It was found that MSCs are captured by the lungs after systemic transplantation, quickly disappear, and are not detected at the site of injury, but at the same time exhibit an obvious therapeutic effect. Comparison of the MSC efficiency depending on the route of their administration may shed light on the mechanisms involved in the implementation of MSC therapeutic potential. In this work, we compared the therapeutic effects of human umbilical cord MSCs (hUC-MSCs) administered systemically and intraperitoneally in the form of MSCs encapsulated in alginate capsules in a CCl4-induced model of liver cirrhosis in rats. Our study showed that both treatments resulted in liver recovery. MSC transplantation by two different routes led to a decrease in collagen deposition, the disappearance of the fibrous area by the 13th week, and normalization of the morphometric parameters of liver parenchyma cells. The expression of some genes (EGF, alpha SMA, GFAP) which is activated in liver injury, decreased to the level observed in negative control animals. However, a detailed study of liver recovery in dynamics showed that encapsulated MSCs led to faster normalization in several parameters of the liver tissue. Our results showed that human umbilical cord MSCs effectively exhibit their therapeutic properties when using both methods of transplantation, however, intraperitoneal administration of encapsulated MSCs accelerated the process of liver regeneration.

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Therapeutic Potential of 47Sc in Comparison to 177Lu and 90Y: Preclinical Investigations

Pharmaceutics ◽

10.3390/pharmaceutics11080424 ◽

2019 ◽

Vol 11 (8) ◽

pp. 424 ◽

Cited By ~ 6

Author(s):

Klaudia Siwowska ◽

Patrycja Guzik ◽

Katharina A. Domnanich ◽

Josep M. Monné Rodríguez ◽

Peter Bernhardt ◽

...

Keyword(s):

Radionuclide Therapy ◽

Therapeutic Potential ◽

Folate Receptor ◽

Tumor Growth Inhibition ◽

Therapeutic Effects ◽

Targeted Radionuclide Therapy ◽

Decay Properties ◽

Therapeutic Properties ◽

Folate Conjugate

Targeted radionuclide therapy with 177Lu- and 90Y-labeled radioconjugates is a clinically-established treatment modality for metastasized cancer. 47Sc is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy β−-particles. In this study, 47Sc was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of 177Lu-folate and 90Y-folate, respectively. In vitro, 47Sc-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to 177Lu-folate, but 90Y-folate was more potent at equal activities due to the higher energy of emitted β−-particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (~21 Gy) when treated with 47Sc-folate (12.5 MBq), 177Lu-folate (10 MBq), and 90Y-folate (5 MBq), respectively. The treatment resulted in increased median survival of 39, 43, and 41 days, respectively, as compared to 26 days in untreated controls. There were no statistically significant differences among the therapeutic effects observed in treated groups. Histological assessment revealed no severe side effects two weeks after application of the radiofolates, even at double the activity used for therapy. Based on the decay properties and our results, 47Sc is likely to be comparable to 177Lu when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with 44Sc or 43Sc as a diagnostic match, enabling the realization of radiotheragnostics in future.

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A Systems Biology Approach in Therapeutic Response Study for Different Dosing Regimens—a Modeling Study of Drug Effects on Tumor Growth using Hybrid Systems

Cancer Informatics ◽

10.4137/cin.s8185 ◽

2012 ◽

Vol 11 ◽

pp. CIN.S8185 ◽

Cited By ~ 3

Author(s):

Xiangfang Li ◽

Lijun Qian ◽

Michale L. Bittner ◽

Edward R. Dougherty

Keyword(s):

Systems Biology ◽

Drug Development ◽

Tumor Growth ◽

Hybrid Systems ◽

Anticancer Agents ◽

Therapeutic Response ◽

Therapeutic Effects ◽

Systems Model ◽

Optimal Drug ◽

Dosing Regimens

Motivated by the frustration of translation of research advances in the molecular and cellular biology of cancer into treatment, this study calls for cross-disciplinary efforts and proposes a methodology of incorporating drug pharmacology information into drug therapeutic response modeling using a computational systems biology approach. The objectives are two fold. The first one is to involve effective mathematical modeling in the drug development stage to incorporate preclinical and clinical data in order to decrease costs of drug development and increase pipeline productivity, since it is extremely expensive and difficult to get the optimal compromise of dosage and schedule through empirical testing. The second objective is to provide valuable suggestions to adjust individual drug dosing regimens to improve therapeutic effects considering most anticancer agents have wide inter-individual pharmacokinetic variability and a narrow therapeutic index. A dynamic hybrid systems model is proposed to study drug antitumor effect from the perspective of tumor growth dynamics, specifically the dosing and schedule of the periodic drug intake, and a drug's pharmacokinetics and pharmacodynamics information are linked together in the proposed model using a state-space approach. It is proved analytically that there exists an optimal drug dosage and interval administration point, and demonstrated through simulation study.

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Functional Microparticles Are up Regulated in Patients with Anti-Heparin/Platelet Factor 4 Antibodies: A Potential Mechanism of Thrombogenesis in the Heparin-Induced Thrombocytopenia Syndrome.

Blood ◽

10.1182/blood.v110.11.2105.2105 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2105-2105

Author(s):

Josephine Cunanan ◽

Michelle Kujawski ◽

He Zhu ◽

Margaret Prechel ◽

Jeanine Walenga ◽

...

Keyword(s):

Platelet Activation ◽

Medical Center ◽

Annexin V ◽

Platelet Factor 4 ◽

Cellular Damage ◽

Clinical Samples ◽

Limiting Factor ◽

Therapeutic Effects ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia

Abstract Heparin-induced thrombocytopenia (HIT) is one of the most catastrophic adverse effects of heparin therapy, representing a complex syndrome involving immunopathologic and hemostatic disorders. Vascular and blood cellular damage results in the generation of microparticles (MP). These MP are formed from stress conditions/cellular disruption and apoptosis. Cellular MP mediated pathophysiologic responses include platelet activation, up regulation of adhesion molecules, monocyte activation, up regulation of tissue factor and endothelial dysfunction. Several methods based on flow cytometric and other immunologic probes have been used to measure MP in the HIT syndrome. Recently, a functional method based on the complexation of MP with annexin V promoting the generation of factor Xa and thrombin has become available (Hyphen Biomedical, Neuville-Oise, France). To validate the hypothesis that functional MP are elevated in the HIT syndrome, this method was utilized for the quantitation of MP in sera ELISA positive for anti-heparin/platelet factor 4 (HIT) antibodies. Specimens (n = 53) were selected from archived samples that had been referred to Loyola University Medical Center for the laboratory diagnosis of HIT by quantitating anti-heparin/PF4 antibodies by ELISA and by evaluating HIT antibody induced platelet activation using the 14C Serotonin Release Assay (SRA). All selected specimens were positive for HIT antibodies in the GTI PF4 Enhanced ELISA with a broad range of antibody titers (absorbance range of 0.4 – 2.5). Eleven of these specimens were positive in the SRA. In addition, serial samples from HIT patients treated with argatroban (from the ARG-911 clinical study) were included (n = 23). The normal samples represented control sera obtained from healthy human volunteers (n = 25) and processed in the same manner as the clinical samples. Test samples were added to microtiter plates coated with streptavidin and biotinylated annexin V. MP present in the test sample bound to annexin V via exposed surface phospholipids. Following incubation and washing steps, a FXa – FVa mixture containing calcium and prothrombin was added. The assay was optimized so that MP associated phospholipid was the limiting factor for the generation of thrombin. In normal non-HIT sera, the MP levels ranged 5.6 – 10.1 nM (6.1 ± 2.8 nM). The pre-treatment, baseline levels of circulating MP in the suspected HIT patients ranged from 4.2 – 26.8 nM (15.8 ± 7.3 nM). Interestingly, SRA positive/ELISA positive samples had relatively higher levels of MP (19.9 ± 7.7 nM; range 11.5 – 29.8 nM) than SRA negative/ELISA positive samples (14.2± 4.6; range 6.8–21.2). In the ARG-911 study, sequential blood samples exhibited MP levels at the baseline ranging from 8.2 – 38.6 nM (21.8 ± 10.8 nM), whereas after 3 days of argatroban treatment were reduced to 5.1 – 19.2 nM (12.6 ± 6.3). The results of these studies suggest that circulating functional MP are increased in patients with ELISA positive HIT antibodies. Anticoagulation with such direct thrombin agents as argatroban effectively decreases the circulating functional MP levels. Since the elevated MP levels may mediate thrombin and FXa generation, the therapeutic effects of these drugs in HIT may be related to the decreased activation of coagulation and related thrombogenic processes.

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Mathematical Modelling and Analysis of the Tumor Treatment Regimens with Pulsed Immunotherapy and Chemotherapy

Computational and Mathematical Methods in Medicine ◽

10.1155/2016/6260474 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Liuyong Pang ◽

Lin Shen ◽

Zhong Zhao

Keyword(s):

Combination Chemotherapy ◽

Half Life ◽

Sufficient Conditions ◽

Effective Concentration ◽

Therapeutic Effects ◽

Chemotherapy Drugs ◽

Treatment Regimens ◽

Mixed Treatment ◽

Therapeutic Results ◽

The Impact

To begin with, in this paper, single immunotherapy, single chemotherapy, and mixed treatment are discussed, and sufficient conditions under which tumor cells will be eliminated ultimately are obtained. We analyze the impacts of the least effective concentration and the half-life of the drug on therapeutic results and then find that increasing the least effective concentration or extending the half-life of the drug can achieve better therapeutic effects. In addition, since most types of tumors are resistant to common chemotherapy drugs, we consider the impact of drug resistance on therapeutic results and propose a new mathematical model to explain the cause of the chemotherapeutic failure using single drug. Based on this, in the end, we explore the therapeutic effects of two-drug combination chemotherapy, as well as mixed immunotherapy with combination chemotherapy. Numerical simulations indicate that combination chemotherapy is very effective in controlling tumor growth. In comparison, mixed immunotherapy with combination chemotherapy can achieve a better treatment effect.

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Evaluation of Human Chorionic Gonadotropin (HCG) Therapeutic Results in Patients With Unilateral cryptorchidism (Undescended Testis)

The Open Urology & Nephrology Journal ◽

10.2174/1874303x02013010013 ◽

2020 ◽

Vol 13 (1) ◽

pp. 13-17

Author(s):

Farzaneh Sharifiaghdas ◽

Sepideh Sharifiaghdas ◽

Esmaeil R. Maleki ◽

Behzad Narouie ◽

Abdolsamad Shikhzadeh ◽

...

Keyword(s):

Undescended Testis ◽

Inguinal Canal ◽

Cost Effective ◽

Therapeutic Effects ◽

Therapeutic Results ◽

Invasive Method ◽

One Year ◽

Retractile Testis ◽

Hcg Therapy ◽

Unilateral Cryptorchidism

Background: Cryptorchidism or undescended testis is an evolutionary defect where one or both testes fail to descend into the scrotum. HCG causes the testes to fail, possibly due to weight gain, an increase in testicular vasculature, and stimulating the testosterone and di-hydro-testosterone. The present study has been conducted to evaluate the therapeutic effects of HCG on patients with unilateral cryptorchidism. Methods: In a prospective descriptive study, 211 patients of 8 months to 7 years old with unilateral cryptorchidism whose parents refused surgery received HCG therapy. The patients were followed up 1 month, 3months, and 12 months after the first injection. They were examined in terms of the location of testes, possible relapses, sides of undescended testes, treatment complications, and HCG therapeutic results. Results: Four weeks after the first injection, 160 patients (75.12%) out of 211 cases had the descent of testes into the inguinal canal and the scrotum. 69.5% of non-palpable abdominal testes descended into the inguinal canal, 69.7% of patients with inguinal testes, 78% of patients with supra inguinal testes and 100% of patients with retractile testis experienced the descent of testes into the scrotum. Conclusion: The therapeutic response to HCG was successful in more than 50% of the cases in all the groups. Therefore, the need for performing surgical procedures on children with unilateral cryptorchidism would be decreased and they can be treated by a cost-effective and less invasive method. Moreover, at least one-year follow-up of the patients is required to ensure outcomes of the treatment.

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Changes in the Transcriptome Profiles of Human Amnion-Derived Mesenchymal Stromal/Stem Cells Induced by Three-Dimensional Culture: A Potential Priming Strategy to Improve Their Properties

International Journal of Molecular Sciences ◽

10.3390/ijms23020863 ◽

2022 ◽

Vol 23 (2) ◽

pp. 863

Author(s):

Alessia Gallo ◽

Nicola Cuscino ◽

Flavia Contino ◽

Matteo Bulati ◽

Mariangela Pampalone ◽

...

Keyword(s):

Stem Cells ◽

Three Dimensional ◽

3D Culture ◽

Therapeutic Effects ◽

Rna Seq ◽

Human Amnion ◽

Cell Based Therapy ◽

Therapeutic Properties ◽

Stromal Stem Cells

Mesenchymal stromal/stem cells (MSCs) are believed to function in vivo as a homeostatic tool that shows therapeutic properties for tissue repair/regeneration. Conventionally, these cells are expanded in two-dimensional (2D) cultures, and, in that case, MSCs undergo genotypic/phenotypic changes resulting in a loss of their therapeutic capabilities. Moreover, several clinical trials using MSCs have shown controversial results with moderate/insufficient therapeutic responses. Different priming methods were tested to improve MSC effects, and three-dimensional (3D) culturing techniques were also examined. MSC spheroids display increased therapeutic properties, and, in this context, it is crucial to understand molecular changes underlying spheroid generation. To address these limitations, we performed RNA-seq on human amnion-derived MSCs (hAMSCs) cultured in both 2D and 3D conditions and examined the transcriptome changes associated with hAMSC spheroid formation. We found a large number of 3D culture-sensitive genes and identified selected genes related to 3D hAMSC therapeutic effects. In particular, we observed that these genes can regulate proliferation/differentiation, as well as immunomodulatory and angiogenic processes. We validated RNA-seq results by qRT-PCR and methylome analysis and investigation of secreted factors. Overall, our results showed that hAMSC spheroid culture represents a promising approach to cell-based therapy that could significantly impact hAMSC application in the field of regenerative medicine.

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RAF1 expression is correlated with HAF, a parameter of liver computed tomographic perfusion, and may predict the early therapeutic response to sorafenib in advanced hepatocellular carcinoma patients

Open Medicine ◽

10.1515/med-2020-0024 ◽

2020 ◽

Vol 15 (1) ◽

pp. 167-174

Author(s):

Ninzi Tian ◽

Dong Wu ◽

Ming Tang ◽

Huichuan Sun ◽

Yuan Ji ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Therapeutic Response ◽

Therapeutic Effects ◽

Advanced Hepatocellular Carcinoma ◽

Sorafenib Treatment ◽

Advanced Hcc ◽

Expression Levels ◽

Portal Vein Flow ◽

Tumor Tissues ◽

Resistant Group

AbstractObjectivesMonitoring the early treatment effect of sorafenib in advanced hepatocellular carcinoma (HCC) patients is a diagnostic challenge. In a previous study, we reported the potential role of liver computed tomography perfusion (CTP) in the assessment of the response to sorafenib therapy in HCC. The present study aims to investigate whether sorafenib-targeted genes is correlated with CTP parameter, and investigate the potential of sorafenib-targeted genes in early prediction of therapeutic response to sorafenib in advanced HCC.MethodsA total of 21 HCC patients were enrolled. Sorafenib was administered orally at a dose of 400 mg twice daily continuously. Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) criteria. CTP scanning was performed before and after two weeks of sorafenib treatment using a 320-detector row CT scanner. The perfusion parameters of portal vein flow (PVF), hepatic artery flow (HAF), and perfusion index (PI) were acquired by CTP. The expression levels of several sorafenib-targeted genes were assayed using real-time quantitative PCR and western blot analysis. Logistic regression was performed to analyze the relationship between HAF values and RAF1 expression levels.ResultsAccording to mRECIST, the disease control rate (CR+PR+SD) of treatment group was 70.5% after two months of treatment. Compared to background controls, tumor tissues exhibited higher HAF. A sorafenib-targeted gene, RAF1 expression, was increased in tumor tissues especially in the sorafenib-resistant group. The sorafenib-resistant group exhibited a significantly higher RAF1 expression and HAF than the sensitive group. Moreover, the RAF1 expression is positively correlated with the HAF value.ConclusionRAF1 expression might predict therapeutic effects of sorafenib in advanced HCC, where RAF1 could potentially serve as a molecular marker for monitoring early therapeutic effects after sorafenib treatment.

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