Synthetic prodrug design enables biocatalytic activation in mice to elicit tumor growth suppression

Considering the intrinsic toxicities of transition metals, their incorporation into drug therapies must operate at minimal amounts while ensuring adequate catalytic activity within complex biological systems. As a way to address this issue, this study investigates the design of synthetic prodrugs that are not only tuned to be harmless, but can be robustly transformed in vivo to reach therapeutically relevant levels. To accomplish this, retrosynthetic prodrug design highlights the potential of naphthylcombretastatin-based prodrugs, which form highly active cytostatic agents via sequential ring-closing metathesis and aromatization. Structural adjustments will also be done to improve aspects related to catalytic reactivity, intrinsic bioactivity, and hydrolytic stability. The developed prodrug therapy is found to possess excellent anticancer activities in cell-based assays. Furthermore, in vivo activation by intravenously administered glycosylated artificial metalloenzymes can also induce significant reduction of implanted tumor growth in mice.

Phytotoxic effects of CdTe quantum dots on root meristems of Allium cepa L.

The effect of solutions of cadmium telluride quantum dots (CdTe QD) as powerful cytotoxic effectors was investigated using a standard Allium cepa L. test system. The diameters of synthesized CdTe QD derived from the optical data varied within 3 – 4 nm. Toxicity of experimental solutions of CdTe QD at the organism level were evaluated by measuring biomass growth of onion roots and cytotoxic influence was estimated based on proliferative activity of root meristem cells. All of CdTe QD experimental solutions in concentration 10 µM significantly inhibited the growth of Allium cepa L. roots, proliferative activity, and total dehydrogenase activity. Relation between the QDs size and their phytotoxicity was not found. However, the highest inhibiting impact was for QDs solution with a nanocrystals size of 3.5 nm. Their ability to penetrate into cells and interact with their intracellular components may cause inhibiting mitosis without fixed clastogenic and aneugenic effects. Solutions of CdTe QD at a given concentration can be considered as potent cytostatic agents for plant cells with antimitotic properties.

Hemophagocytic Lymphohistiocytosis in Children

Objective of the Paper: To present a clinical case of a 2.5-year girl hospitalised with severe pneumonia with associated hemophagocytic lymphohistiocytosis (HLH). Key Points. HLH is a syndrome, the clinical representation of which is a system sepsis-like inflammatory reaction; in the majority of cases, this condition is hardly diagnosed by paediatricians. Associated pancytopenia and hyperferritinaemia are of diagnostic importance. Here we present a clinical case of a 2.5-year girl who was hospitalised with severe pneumonia and associated HLH. As there is no common approach to the management of HLH, we summoned a board of doctors and decided to start steroid therapy (dexamethasone) and IV immunoglobulin (Octagam), and if there was no effect from therapy within a week, cytostatic agents would be added. The therapy was initiated promptly after macrophages had been found in bone marrow smear. Clinical and paraclinic improvements were noted on day 5, so aggressive immunosuppresion was not initiated. In a month there were no signs of organ dysfunction; the values normalised, and the child was discharged from the inpatient clinic. Conclusion. HLH is associated with high mortality, therefore, early diagnosis and therapy are critical. The specificity of this case is that we managed to promptly diagnose the condition, initiated treatment and achieved complete remission without aggressive immunosuppresion. Keywords: hemophagocytic lymphohistiocytosis, macrophages, pancytopenia.

A Case Report on Canine Transmissible Venereal Tumor

Background: A male Japanese spitz (3 years) was brought at Himalayan Animal Rescue Trust (HART), Pokhara with a complaint of swollen gums and loss of appetite. A lobulated tumorous mass was seen at the gingival region on physical examination.Objectives: Diagnosis and treatment of condition detected in the dog was the major objective.Methods: Impression smear of tumor cell was prepared and was observed under oil immersion microscope (100x).Results: Microscopic examination shows the presence of vacuolations within the cytoplasm and the condition was diagnosed to be CTVT.Treatment: Chemotherapy was performed using the most effective cytostatic agents I.e. Vincristine sulphate (once a week, I/v). The chemotherapy was repeated for 3 doses till the tumor gets completely regressed.Conclusion: The condition was resolved after third session of chemotherapy. Myelosuppression and gastrointestinal effects like vomiting are the major complications of using vincristine.

Polyphenols as Possible Agents for Pancreatic Diseases

Pancreatic cancer (PC) is very aggressive and it is estimated that it kills nearly 50% of patients within the first six months. The lack of symptoms specific to this disease prevents early diagnosis and treatment. Today, gemcitabine alone or in combination with other cytostatic agents such as cisplatin (Cis), 5-fluorouracil (5-FU), irinotecan, capecitabine, or oxaliplatin (Oxa) is used in conventional therapy. Outgoing literature provides data on the use of polyphenols, biologically active compounds, in the treatment of pancreatic cancer and the prevention of acute pancreatitis. Therefore, the first part of this review gives a brief overview of the state of pancreatic disease as well as the procedures for its treatment. The second part provides a detailed overview of the research regarding the anticancer effects of both pure polyphenols and their plant extracts. The results regarding the antiproliferative, antimetastatic, as well as inhibitory effects of polyphenols against PC cell lines as well as the prevention of acute pancreatitis are presented in detail. Finally, particular emphasis is given to the polyphenolic profiles of apples, berries, cherries, sour cherries, and grapes, given the fact that these fruits are rich in polyphenols and anthocyanins. Polyphenolic profiles, the content of individual polyphenols, and their relationships are discussed. Based on this, significant data can be obtained regarding the amount of fruit that should be consumed daily to achieve a therapeutic effect.

Palliative Electrochemotherapy Treatment of Cutaneous Metastases in a Patient with Advanced Thyroid Papillary Carcinoma

Advanced papillary thyroid carcinoma (PTC) with cutaneous metastases may cause pain, ulceration, and bleeding. Electrochemotherapy (ECT) is a minimally invasive treatment of tumors located in the skin and subcutaneous tissue. The electric pulses potentiate the toxicity of cytostatic agents entering the tumor cell. It is highly effective especially to relieve pain and improve the quality of life. The adverse events are local and transient. A case of progressive metastatic PTC who developed bleeding cutaneous metastases treated with ECT is described.

ANTIBODY-DRUG CONJUGATES FOR TARGETED CANCER THERAPY

Monoclonal antibody (MAB) conjugates with cytostatic agents (ADC) are intended for selective delivery of a cytostatic agent to a tumor cell. Three ADC have been approved for clinical use (gemtuzumab ozogamicin, brentuximab vedotin, trastuzumab-DM1); a few dozens of other ADC are undergoing clinical trials. Several derivatives of natural substances (antibiotics and inhibitors of microtubules) having a high antitumor activity are used as cytostatic agents included in ADC. They are inapplicable in clinical practice as self-sustained drugs due to their considerable toxicity. Of great importance for the implementation of the ADC effect is the character of a linker connecting MAB with a cytostatic agent and ensuring selective intracellular release after ADC internalization. The structure, mechanisms of action, and the results of clinical trials of a number of ADC are considered here as an illustration (by way of example). The development of ADC can help introduce new effective cytostatic agents into clinical practice.