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Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Vinblastine is also a vinca alkaloid derived from the periwinkle plant. It is indicated for the treatment of HL and NHL, breast cancer, Kaposi’s sarcoma, and renal cell carcinoma. It exerts its antitumor effect by inhibiting tubulin polymerization and disrupting microtubules during the M-phase of the cell cycle. As with most agents described here, animal studies in early pregnancy have demonstrated increased resorption, spontaneous abortion, and gross fetal abnormalities. However, some human studies have reported no teratogenic effects from first-trimester exposure (90). At 18 weeks of gestation, a patient was diagnosed with an endodermal sinus tumor of the ovary, and following laparotomy, she received three courses of cisplatin, vinblastine, and bleomycin (69). She delivered a healthy and normal infant at 31 weeks. To date, there have been more than half a dozen other patients who have received vinblastine in combination regimens, followed by the delivery of normal, healthy infants (91,92).
Antitubulin Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
These alkaloids were discovered through in vivo screens for antidiabetic activity which showed that the plant extracts reduced white blood cell counts in mouse models. This prompted an investigation into their anticancer properties, particularly as potential antileukemic agents. The isolated alkaloids, vinblastine and vincristine, and the related semisynthetic agents vindesine, vinorelbine, and vinflunine (Figure 4.7) are used to treat a variety of cancers, including the acute leukemias (e.g., acute lymphocytic leukemia [ALL]) and lymphomas (e.g., Hodgkin’s and non-Hodgkin’s lymphoma, and mycosis fungoides), and some solid tumors (e.g., breast, testicular, and lung cancers, neuroblastoma, histiocytosis, and Kaposi’s sarcoma). Structures of the Vinca alkaloids vinblastine and vincristine, and their three semisynthetic analogues, vindesine, vinorelbine, and vinflunine.
Herbs in Cancer Therapy
Published in Anil K. Sharma, Raj K. Keservani, Surya Prakash Gautam, Herbal Product Development, 2020
Annum Malik, Shahzadi Sidra Saleem, Kifayat Ullah Shah, Learn-Han Lee, Bey Hing Goh, Tahir Mehmood Khan
Two important classes of the tubulin-binding agents include Vinca alkaloids and taxanes. Vinca alkaloids are microtubule-targeting drugs which binds with ɑ/β-tubulin dimers and as a result destabilized the microtubules. (Hassan and MA). Recent evidence indicates that microtubule function is disrupted by both kinds of drugs including taxanes that are known to be microtubule stabilizing drugs and vinca alkaloids that are considered as microtubule destabilizing drugs (Escuin et al. 2005). Hence, they prevent the proper alignment of daughter chromosomes to the microtubules. This disruption in proper alignment of daughter chromosomes on microtubules results in the inhibition of phases of mitotic cell division, particularly metaphase and anaphase. Such inhibition of cell division or particularly called cell cycle arrest may ultimately be followed by apoptosis (Nobili et al. 2009). For example, vinca alkaloids prevents cell cycle progression and induce mitotic block and apoptosis. Whatever the concentration of vinca alkaloids, mitochondria appear to be at the point of convergence for the apoptotic signals (Pourroy et al. 2004). Podophyllotoxin binds to microtubules, thus preventing their formation and destabilizing them (Darwiche et al. 2007).
A novel hepatoprotective activity of Alangium salviifolium in mouse model
Published in Drug and Chemical Toxicology, 2022
Preeti Dhruve, Mohd Nauman, Raosaheb K. Kale, Rana P. Singh
The bark decoction of A. salviifolium is used traditionally to treat cancerous wounds (Jain and Jain 2010). The decoction contains mostly oil and volatile organic compounds, and thus GC-MS analysis of methanolic BEA was carried out to analyze the phytoconstituents. Thirty seven compounds that were identified in GC-MS analysis of BEA contained fatty acids, alkaloids, and plant steroids. Among alkaloids, vinca alkaloids (vinblastine, vincristine, and vindesine) was a major class of plant-derived anticancer agents (Taneja and Qazi 2007). Alkaloids like piperine have already been reported for its hepatoprotective and chemopreventive effects (Darshan and Doreswamy 2004, Selvendiran and Sakthisekaran 2004, Rather and Bhagat 2018). Previous studies on plant sterols especially γ-sitosterol have shown to decrease the CCl4-induced liver damage as AST and ALT were decreased with an increase in catalase activity. Stigmasterol treatment to mice receiving a carcinogen, DMBA, and promoter croton oil, caused a reduction in tumor size and average number of papilloma along with a decrease in AST, ALT, and ALP; with a concomitant increase in glutathione, SOD, and CAT activities (Ali et al.2015, Tiwary et al. 2017). Therefore, these identified plant alkaloids and sterols may contribute to the hepatoprotective and antioxidant activities of BEA.
Redox-sensitive TRP channels: a promising pharmacological target in chemotherapy-induced peripheral neuropathy
Published in Expert Opinion on Therapeutic Targets, 2021
Ramandeep Singh, Pratik Adhya, Shyam Sunder Sharma
Interference with microtubule functioning is crucial for the anti-cancer action of a wide variety of chemotherapeutic agents. Chemotherapeutic agents like vinca alkaloids (vincristine and vinblastine), taxanes (paclitaxel and docetaxel), and epothilones (ixabepilone) constitute the group of microtubules targeting agents. Vinca alkaloids are reported to destabilize the microtubule fibrils by preventing microtubule polymerization, whereas taxanes by interacting with tubulin protein, stabilizes the microtubule and inhibit its disassembly [75]. Although the mechanism of epothilones is poorly understood, however, they are reported to disrupt the microtubule of the mitotic spindles of long axons leading to the development of epothilones-induced peripheral neuropathy [76]. Reports suggested that Vincristine, paclitaxel, ixabepilone, and eribulin causes neuropathy by damaging the microtubule-based long axonal transport in sensory neurons [77]. Impairment in axonal transport leads to scarcity in the supply of essential nutrients involved in synapse formation and maintenance [78]. Moreover, vincristine-induced microtubules damage in oligodendrocytes results in abnormal myelination of sensory nerve fibers which can subsequently lead to peripheral neuropathy [79]. Recently, Bortezomib-induced peripheral neuropathy is also reported to be dependent on its effect on microtubule stability in sensory neurons. Bortezomib disrupts axonal motility of mitochondria through the accumulation of delta 2 tubulins [80,81].
Update on diagnosis and treatment of immune thrombocytopenia
Published in Expert Review of Clinical Pharmacology, 2021
Rajeev Sandal, Kundan Mishra, Aditya Jandial, Kamal Kant Sahu, Ahmad Daniyal Siddiqui
In pregnancy, differential diagnoses for thrombocytopenia include gestational thrombocytopenia, pregnancy-related hypertensive disorders like eclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count). Once the diagnosis of ITP is established, the patient should be kept on close follow up for bleeding with target platelet count >30 × 109/L till term. The mode of delivery is guided by the obstetrician’s choice. For normal delivery, the platelet count should be kept >50 × 109/L, and for cesarean section it should be maintained >70 × 109/L for safe spinal anesthesia. Drugs preferred in pregnancy are IVIG and corticosteroids. Patients are usually started on prednisolone at 20 mg daily and the patient is kept on a minimum dose to maintain target platelets to avoid unnecessary side effects. IVIG at dose 1–2 gm/kg can be used if the fast response is required near term. Anti-D can be also used in non-splenectomized patients after documenting negative direct coombs test. In refractory cases, combination therapies comprising of high-dose corticosteroid (dexamethasone) with IVIG or azathioprine, or cyclosporine with azathioprine can be used. The published experience with TPO-RAs in pregnancy is limited to case reports only. Rituximab increases the risk of immunosuppression in the newborn, so its use is not recommended. If a patient needs splenectomy for refractory ITP, it should be preferably performed during the second trimester. Vinca alkaloids, mycophenolate and cyclophosphamide should not be used during pregnancy [7,8,12,181].