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| Mechanism of action of vincristine, paclitaxel, oxaliplatin and cisplatin. Anti-tumor mechanism of action of vincristine, paclitaxel, oxaliplatin and cisplatin leading to cell arrest and cell death. (A) Vincristine prevents microtubule aggregation, whereas paclitaxel prevents microtubule disaggregation, an effect leading to cancer cell division arrest and cell death. (B) Oxaliplatin and cisplatin bind to nuclear DNA (deoxyribonucleic acid) of cancer cells, causing disruption of DNA replication and RNA (ribonucleic acid) transcription and subsequent arrest of cancer cell division. The DNA adducts activate apoptotic pathways that induce cell death and tumor degradation. (C) All four anti-tumor agents alter the function of mitochondria, followed by disruption of respiratory chain function and increased production of reactive oxygen species (ROS). Additionally, oxaliplatin and cisplatin cause damage to cancer cell mitochondria by binding to mitochondrial DNA, altering mDNA replication and transcription. (D) All four agents cause activation of immune cells, an effect likely contributing to tumor cell degradation. Only a few representative immune cell-types are shown.
Source publication
Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic...
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... Additionally, these agents alter the respiratory chain by altering the function of mitochondria, leading to the production of ROS (reactive oxygen species). Also, oxaliplatin and cisplatin bind to mitochondrial DNA and interfere with its replication and transcription [44]. These mechanisms are the most common for metal complexes and affect the G0/G1 phase. ...
Drug resistance in infectious diseases developed by bacteria and fungi is an important issue since it is necessary to further develop novel compounds with biological activity that counteract this problem. In addition, new pharmaceutical compounds with lower secondary effects to treat cancer are needed. Coordination compounds appear to be accessible and promising alternatives aiming to overcome these problems. In this review, we summarize the recent literature on coordination
compounds based on nitrobenzoic acid (NBA) as a ligand, its derivatives, and other nitrocontaining ligands, which are widely employed owing to their versatility. Additionally, an analysis of crystallographic data is presented, unraveling the coordination preferences and the most effective crystallization methods to grow crystals of good quality. This underscores the significance of elucidating
crystalline structures and utilizing computational calculations to deepen the comprehension of the electronic properties of coordination complexes.
... Among these 38 patients, a total of 64 adverse events were described. The most common adverse event reported was abdominal pain, at 25% (95% CI, [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Nausea and vomiting were the next most common adverse events, occurring in 23% (95% CI, 14-34) and 16% (95% CI, 8-24) of patients, respectively. ...
... Expectedly, we found a lower rate of response in patients who had received a dose of vinca alkaloids in the 30 days prior to methylnaltrexone administration. It is well understood that constipation related to the use of vinca alkaloids is due to autonomic neuropathy, which differs from OIC. 24 When constipation is due to autonomic neuropathy secondary to vinca alkaloid use, the response to laxatives is often diminished, with up to 40% of patients reportedly not experiencing improvement with laxative use. 25 Because the pathophysiology of autonomic neuropathy is different from that of OIC, we would not expect an opioid antagonist to alleviate constipation associated with vinca alkaloid use, and this would be demonstrated by a lower response rate with methylnaltrexone use in this patient cohort. ...
OBJECTIVES
Constipation is a common adverse event of opioid use that is often difficult to treat. Methylnaltrexone is a therapeutic option for opioid-induced constipation (OIC) approved for oral and subcutaneous use in adults. These administration routes are not always feasible in the pediatric population. The primary objective of this research was to quantify the response rate of methylnaltrexone in pediatric patients when it was administered via the intravenous (IV) route.
METHODS
This retrospective study evaluated patients ages <18 years who received IV methylnaltrexone between January 1, 2013, and June 30, 2020, for OIC. Efficacy was evaluated through documentation of bowel evacuation within 4 hours of methylnaltrexone administration. Adverse events observed within 24 hours of administration were attributed to methylnaltrexone.
RESULTS
Methylnaltrexone was administered to 134 unique patients during the study period. Of these, 46 met exclusion criteria, resulting in 88 patients being included in the study. Patients with an underlying hematology/oncology diagnosis consisted of 77% of the study population, and 23% of patients had an underlying medical/surgical diagnosis. The response rate to IV methylnaltrexone was 25% (CI, 16–34).
CONCLUSIONS
The results of this retrospective chart review demonstrate the potential role of IV methylnaltrexone in the pediatric population. Despite the overall lower response rate relative to that reported in adults, IV methylnaltrexone possesses a unique mechanism of action that may serve as an alternative treatment option for patients unable to use the oral and subcutaneous administration routes. There were no significant adverse events seen in the study.
... Chemotherapy-induced peripheral neuropathy (CIPN) represents one of the most challenging side effects to overcome, as agents, like this one, cause damage to peripheral nerves, which in turn leads to numbness, tingling, and pain in different body parts of the patient (5) . The treatment of these problems may serve for the variety of clinical symptoms, which can negatively impact life quality of a patient significantly, making physically impossible to walk, write or even hold a cup (2) The scope of the CIPN is determined by different factors and including the chemotherapeutic agent type, the overall dose, and individual's genetic disposition (6) . Some chemotherapeutic drugs, like platinum derivative compounds (e. g. "cisplatin"), are used in treating ovarian cancers. ...
This case study evaluates the impact of a multidisciplinary rehabilitation approach combining Dance/Movement Therapy (DMT) and psychological motion therapy on an ovarian cancer patient having chemotherapy-induced peripheral neuropathy (CIPN). The patient, U.B, had a five-week intervention targeted at improving physical functioning, lowering neuropathic pain, and raising overall quality of life. Baseline assessments included tests of grip strength, knee and shoulder flexion, psychological well-being using the Hospital Anxiety and Depression Scale (HADS), neuropathic pain using the DN4 scale, and quality of life using the EORTC QLQ-C30. The intervention comprised weekly sessions integrating DMT and psychological approaches, followed by weekly examinations to track development. Results demonstrated considerable increases in physical functioning, with grip strength increasing by 4 kg in both hands and notable advances in knee and shoulder flexion. Psychological well-being showed great progress, with HADS ratings for anxiety and depression falling significantly. The DN4 neuropathic pain score reduced from 8 to 5, showing a considerable reduction in pain. Quality of life metrics improved across several areas, including physical activities, work and leisure, and general health. The overall health score climbed from 4 to 6, while the quality-of-life score improved from 3 to 5. This study illustrates the usefulness of a holistic rehabilitation approach in treating CIPN and enhancing the quality of life for ovarian cancer patients. The confluence of physical and psychological therapy offers a complete strategy for treating the numerous issues associated with CIPN. These findings imply that multidisciplinary therapies should be used in cancer rehabilitation programs to enhance patient outcomes. Further study with larger samples and randomized controlled trials is necessary to validate these results and explore the long-term advantages of such therapies.
... Terdapat enam kelompok agen kemoterapi utama yang dapat menyebabkan kerusakan pada neuron sensorik, motorik, dan otonom perifer, sehingga muncul manifestasi gangguan saraf tepi: antineoplastik berbasis platinum (terutama oxaliplatin dan cisplatin), alkaloid vinca (terutama vincristine dan vinblastine), epothilone (ixabepilone), taksan (paclitaxel, docetaxel), penghambat proteasom (bortezomib), dan obat imunomodulator (thalidomide) (Starobova & Vetter, 2017). Tidak ada penanda biologis (biomarker) yang spesifik untuk menilai dan mendiagnosis gangguan saraf tepi pada pasien atau untuk memprediksi kerentanan dan tingkat keparahan gejala gangguan saraf tepi berdasarkan durasi atau dosis kemoterapi (Ibrahim & Ehrlich, 2020). ...
Neuropati perifer adalah gangguan serabut saraf tepi akibat sekunder dari berbagai proses patologis seperti diabetes melitus, kekurangan vitamin maupun obat-obatan seperti obat kemoterapi. Gejala klinis berupa gangguan motorik, sensorik, dan gangguan otonom. Pasien kanker yang menjalani kemoterapi rentan mengalami gejala neuropati perifer yang disebabkan oleh perubahan anatomis (seperti degenerasi aksonal distal) atau perubahan fisiologis. Untuk itu diperlukan edukasi terkait neuropati perifer pada pasien yang menjalani kemoterapi. Kegiatan ini bertujuan untuk meningkatkan pengetahuan pasien poli onkologi mengenai efek samping penggunaan obat kemoterapi, seperti gangguan saraf tepi. Kegiatan pengabdian masyarakat ini dilaksanakan di Gedung Onkologi Rumah Sakit Umum Daerah (RSUD) Provinsi Nusa Tenggara Barat (NTB). Implementasi kegiatan mengenai edukasi gangguan saraf tepi akibat obat kemoterapi dilakukan dengan memberikan pre-test, penyampaian materi edukasi, post-test, dan diskusi. Edukasi ini diikuti oleh tiga puluh orang partisipan yang merupakan pasien poli onkologi RSUD Provinsi NTB. Pada kegiatan pretest didapatkan masih banyak partisipan belum mengetahui gangguan saraf tepi akibat efek samping obat. Pada post-test, skor pengetahuan diatas rata-rata (100%) terkait gangguan saraf tepi akibat efek samping obat. Hal ini menunjukkan efektivitas edukasi dan metode yang digunakan. Terdapat peningkatan pemahaman pasien poli onkologi pada RSUD Provinsi NTB terkait neuropati akibat efek samping obat kemoterapi.
... 7,40 Based on preclinical evidence, oxidative stress, interference with tubulin with damage to the cytoskeleton and impairment in axonal transport, neuronal drug accumulation due to the activity of specific transporters, and neuroinflammation have been suggested as possible pathogenic events. 4,17,18,35,36,38 Despite intense investigation using in vitro cellular systems, the use of animal models remains essential in experimental CIPN. 44 However, some of these models reproduce only partially the clinical picture of the tested drugs, thus raising concern when the preclinical results are translated into clinical practice. ...
Paclitaxel-induced peripheral neurotoxicity (PIPN) is a potentially dose-limiting side effect in anticancer chemotherapy. Several animal models of PIPN exist, but their results are sometimes difficult to be translated into the clinical setting. We compared 2 widely used PIPN models characterized by marked differences in their methodologies. Female C57BL/6JOlaHsd mice were used, and they received only paclitaxel vehicle (n = 38) or paclitaxel via intravenous injection (n = 19, 70 mg/kg) once a week for 4 weeks (Study 1) or intraperitoneally (n = 19, 10 mg/kg) every 2 days for 7 times (Study 2). At the end of treatment and in the follow-up, mice underwent behavioral and neurophysiological assessments of PIPN. At the same time points, some mice were killed and dorsal root ganglia, skin, and sciatic and caudal nerve samples underwent pathological examination. Serum neurofilament light levels were also measured. The differences in the neurotoxicity parameters were analyzed using a nonparametric Mann-Whitney test, with significance level set at P < 0.05. Study 1 showed significant and consistent behavioral, neurophysiological, pathological, and serological changes induced by paclitaxel administration at the end of treatment, and most of these changes were still evident in the follow-up period. By contrast, study 2 evidenced only a transient small fiber neuropathy, associated with neuropathic pain. Our comparative study clearly distinguished a PIPN model recapitulating all the clinical features of the human condition and a model showing only small fiber neuropathy with neuropathic pain induced by paclitaxel.
... It provides an effect contributing to the degradation of cancer cells through the activation of the immune system and apoptotic pathway. Another mechanism involves interfering with the synthesis of protein & nucleic acid (NA) by blocking the utilization of glutamic acid [50][51][52][53][54][55]. ...
From the ancient period, nature has always blessed human beings with a variety of medicinal plants having no or less side effects. Catharanthus roseus (Apocyanceae) is a well-known ayurvedic herb that can be found in vast quantities all around the world. The common name for C. roseus are periwinkle, pink periwinkle, Madagascar periwinkle, old maid, graveyard plant, cape periwinkle, and bright eyes. The present research has aimed to review the presence of phytochemicals, ethnopharmacological, traditional, and important medicinal information on C. roseus. This plant has traditionally been used to treat muscle discomfort, central nervous system depression, and wasp stings. Recent research has revealed that C. roseus contains more than 70 different types of alkaloids (indole alkaloids), saponins, flavonoids, carbohydrates, and chemotherapeutic agents that are effective in treating life-threatening diseases like cancers. The phytoconstituents present in C. roseus exhibited antidiabetic, anticancer, antiulcer, antioxidant, antibacterial, and other pharmacological effects in different in vitro and in vivo studies. Vinca alkaloids (vincristine and vinblastine) are one of the prominent phytoconstituents present in this plant which highly contribute to cancer chemotherapy. This mini-review will provide valid and crucial information about C. roseus to future research in natural drug discovery processes and also for clinical researchers to find vital and effective medication to treat life-threatening conditions.
... 96% of chemotherapy patients develop peripheral neuropathy such as numbness and tingling due to axonal degeneration caused by systemic administration of Vcr [54,[73][74][75]. In mouse models, locally injecting Vcr into the hind paw resulted in transient mechanical hypersensitivity but later transitioned into long-term hyposensitivity or loss of sensation [76]. Treatment of dissociated DRG neurons from rodents demonstrated neurite fragmentation and loss of neurite processes [50,77]; however, the DRG dissociation process removes support cells from culture that may be necessary for axonal dieback. ...
Low back pain, knee osteoarthritis, and cancer patients suffer from chronic pain. Aberrant nerve growth into intervertebral disc, knee, and tumors, are common pathologies that lead to these chronic pain conditions. Axonal dieback induced by capsaicin (Caps) denervation has been FDA-approved to treat painful neuropathies and knee osteoarthritis but with short-term efficacy and discomfort. Herein, we propose to evaluate pyridoxine (Pyr), vincristine sulfate (Vcr) and ionomycin (Imy) as axonal dieback compounds for denervation with potential to alleviate pain. Previous literature suggests Pyr, Vcr, and Imy can cause undesired axonal degeneration, but no previous work has evaluated axonal dieback and cytotoxicity on adult rat dorsal root ganglia (DRG) explants. Thus, we performed axonal dieback screening using adult rat DRG explants in vitro with Caps as a positive control and assessed cytotoxicity. Imy inhibited axonal outgrowth and slowed axonal dieback, while Pyr and Vcr at high concentrations produced significant reduction in axon length and robust axonal dieback within three days. DRGs treated with Caps, Vcr, or Imy had increased DRG cytotoxicity compared to matched controls, but overall cytotoxicity was minimal and at least 88% lower compared to lysed DRGs. Pyr did not lead to any DRG cytotoxicity. Further, neither Pyr nor Vcr triggered intervertebral disc cell death or affected cellular metabolic activity after three days of incubation in vitro. Overall, our findings suggest Pyr and Vcr are not toxic to DRGs and intervertebral disc cells, and there is potential for repurposing these compounds for axonal dieback compounds to cause local denervation and alleviate pain.
... Underlying risk factors of ciPN include history of smoking, age, reduced creatinine clearance from the body, neurotoxic chemotherapeutic drugs, and independent cancer-associated neuropathy (Seretny et al. 2014). Six primary chemical groups causing ciPN are platinum-based antineoplastics, taxanes, immunomodulatory drugs, vinca alkaloids, epothilones, and proteasome inhibitors (Starobova and vetter 2017). the etiopathogenesis of ciPN is multifactorial. ...
... Altered neuronal excitability in ciPN is further exacerbated by the effects of potassium (K+) channels that are expressed in peripheral nerves. the four major groups consist of the ca2+-activated K + channels (Kca), voltage-gated K + channels (Kv), inwardly rectifying K + channels (Kir) and two-pore K + channels (K2P) (Starobova and vetter 2017). thalidomide is used in multiple myeloma, but activation of certain pathways eventually damages neurons and leads to PN (Figure 2b). the detailed mechanisms of PN induced by various chemotherapeutic drugs are given below. ...
... It is widely used in traditional Chinese medicine to treat diabetes, gastrointestinal diseases and also used as anti-cancer drug with its flower and stalk portions in dried form for the cooking of herbal soup [2]. However, Catharanthus roseus toxicity can lead to bone marrow suppression, gastrointestinal toxicity, paresthesia, stomatitis, fever, and even cause multi-organ failure [3,4]. We herein report a case of Catharanthus roseus juice toxicity presenting as acute cholangitis. ...
... and vinorelbine which is widely used for chemotherapy, mainly for hematological malignancies [1]. The toxicity of Catharanthus roseus includes bone marrow suppression and gastrointestinal toxicity, similar to the toxic effects of these vinca alkaloids, but also includes paresthesia, stomatitis, fever and could lead to multi-organ failure [3,4]. Our case presented with symptoms of lower leg numbness indicative of neurotoxicity following the ingestion of Catharanthus roseus. ...
Background
Catharanthus roseus, a Madagascar native flowering plant, is known for its glossy leaves and vibrant flowers, and its medicinal significance due to its alkaloid compounds. As a source of vinblastine and vincristine used in chemotherapy, Catharanthus roseus is also employed in traditional medicine with its flower and stalks in dried form. Its toxicity can lead to various adverse effects. We report a case of Catharanthus roseus juice toxicity presenting as acute cholangitis, emphasizing the importance of healthcare providers obtaining detailed herbal supplement histories.
Case presentation
A 65-year-old woman presented with abdominal pain, fever, anorexia, and lower limb numbness. Initial diagnosis of acute cholangitis was considered, but imaging excluded common bile duct stones. Further investigation revealed a history of ingesting Catharanthus roseus juice for neck pain. Laboratory findings showed leukocytosis, elevated liver enzymes, and hyperbilirubinemia. The patient developed gastric ulcers, possibly due to alkaloids in Catharanthus roseus. No bacterial growth was noted in blood cultures. The patient recovered after discontinuing the herbal extract.
Conclusions
Catharanthus roseus toxicity can manifest as fever, hepatotoxicity with cholestatic jaundice, and gastric ulcers, mimicking acute cholangitis. Awareness of herbal supplement use and potential toxicities is crucial for healthcare providers to ensure prompt diagnosis and appropriate management. This case emphasizes the need for public awareness regarding the possible toxicity of therapeutic herbs and the importance of comprehensive patient histories in healthcare settings.
... Нарушения чувствительности, как правило, составляют основную часть клинической картины ХИПН и явля-ются преобладающим проявлением данного осложнения [7]. Большинство пациентов сталкивается с нарушениями чувствительности уже в первый месяц противоопухолевого лечения [21]. Существующие данные свидетельствуют о возрастании риска развития нейропатии по мере увеличения суммарной дозы химиотерапевтических препаратов. ...
Chemotherapy-related peripheral neuropathy (CIPN) is a complication which occurs in the most cancer patients receiving taxanes and platinum-based systemic therapy. CIPN includes the wide range of clinical symptoms, and the peripheral sensitive disorders are the most common. Some patients have CIPN-related symptoms persistent after chemotherapy completion. Impact on patient's quality of life and high prevalence among cancer patients make an active search for new ways of CIPN medical correction relevant. We reviewed the existing data on medical prophylaxis and treatment of CIPN and also presented our observation data with CIPN patients. Based on our research results, we showed that the impact of CIPN on a patient's quality's life was spread beyond the peripheral sensitivity disorder. This should be taken into account for further studying of the possible correction of CIPN.
