scholarly journals Cisplatin induced neurotoxicity is mediated by Sarm1 and calpain activation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Aysel Cetinkaya-Fisgin ◽  
Xinghua Luan ◽  
Nicole Reed ◽  
Ye Eun Jeong ◽  
Byoung Chol Oh ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Side Effects ◽  
Cancer Cells ◽  
Wallerian Degeneration ◽  
Axonal Degeneration ◽  
Adduct Formation ◽  
Calpain Activation ◽  
Chemotherapy Agent ◽  
Distal Axonal Degeneration ◽  
Calpain Inhibitors

AbstractCisplatin is a commonly used chemotherapy agent with significant dose-limiting neurotoxicity resulting in peripheral neuropathy. Although it is postulated that formation of DNA-platinum adducts is responsible for both its cytotoxicity in cancer cells and side effects in neurons, downstream mechanisms that lead to distal axonal degeneration are unknown. Here we show that activation of calpains is required for both neurotoxicity and formation of DNA-platinum adduct formation in neurons but not in cancer cells. Furthermore, we show that neurotoxicity of cisplatin requires activation of Sarm1, a key regulator of Wallerian degeneration, as mice lacking the Sarm1 gene do not develop peripheral neuropathy as evaluated by both behavioral or pathological measures. These findings indicate that Sarm1 and/or specific calpain inhibitors could be developed to prevent cisplatin induced peripheral neuropathy.

scholarly journals Acupuncture Treatment for Bortezomib-Induced Peripheral Neuropathy: A Case Report

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Ting Bao ◽  
Ruixin Zhang ◽  
Ashraf Badros ◽  
Lixing Lao
Keyword(s):  
Multiple Myeloma ◽  
Case Report ◽  
Peripheral Neuropathy ◽  
Side Effects ◽  
Diabetic Neuropathy ◽  
Side Effect ◽  
Acupuncture Treatment ◽  
Chemotherapy Agent ◽  
Successful Case

Peripheral neuropathy is a common and severe dose-limiting side effect of the chemotherapy agent, bortezomib, in multiple myeloma patients. Treatment with narcotics, antidepressants, and anticonvulsants has limited response and potential significant side effects. Acupuncture has been reported to be effective in treating diabetic neuropathy and chemo-induced peripheral neuropathy. There has not been report on the effect of acupuncture in treating bortezomib-induced peripheral neuropathy specifically. Here, we report a successful case of using acupuncture to relieve bortezomib-induced peripheral neuropathy symptoms.

Molecular Studies on Novel Antitumor Bis 1,4-Dihydropyridine Derivatives Against Lung Carcinoma and their Limited Side Effects on Normal Melanocytes

2019 ◽  
Vol 18 (15) ◽  
pp. 2156-2168 ◽  
Author(s):  
Magda F. Mohamed ◽  
Nada S. Ibrahim ◽  
Ahmed H.M. Elwahy ◽  
Ismail A. Abdelhamid
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Cells ◽  
Cell Line ◽  
Lung Carcinoma ◽  
Carcinoma Cell ◽  
Normal Cells ◽  
Lung Carcinoma Cell Line ◽  
Molecular Studies ◽  
Dihydropyridine Derivatives

Background: Cancer is a complex genetic disease which is characterized by an abnormal cell growth, invasion and spreading to other parts of the body. There are several factors that lead to cancer by causing DNA damage and the impairment of its repair. Treatment of cancer using the chemotherapeutic drugs have adverse side effects such as toxicity as they lose their specificity toward cancer cells and affect also normal cells. Moreover, the cancer cells can resist the chemotherapeutic agents and make them ineffective. For these reasons, much attentions have been paid to develop new drugs with limited side effects on normal cells and to diminish cancer resistance to drug chemotherapy. Recently, some 1,4-dihydropyridine derivatives were reported to act as Multi-Drug Resistance (MDR) modulators that inhibit p-glycoprotein which is responsible for the inability of drugs to enter the cancer cells. Also 1,4-DHPs have antimutagenic properties against chemicals via modulating DNA repair when studied on drosophila. Objective: The objective of this study is the synthesis of bis 1,4-DHPs incorporating ester as well as ether linkages and evaluate the anticancer activity of new compounds for synergistic purpose. Different genetic tools were used in an attempt to know the mechanism of action of this compound against lung cancer. Method: An efficient one pot synthesis of bis 1,4-DHPs using 3-aminocrotononitrile and bis(aldehydes) has been developed. The cytotoxic effect against human cell lines MCF7, and A549 cell lines was evaluated. Results: All compounds exhibited better cytotoxicity toward lung carcinoma cells than breast cancer cells. With respect to lung carcinoma cell line (A549), compound 10 was the most active compound and the three other compounds 7, 8, and 9 showed comparable IC50 values. In case of breast cancer cell line (MCF7), the most active one was compound 7, while compound 8 recorded the least activity. Conclusion: we have developed an efficient method for the synthesis of novel bis 1,4-dihydropyridine derivatives incorporating ester or ether linkage. All compounds showed better cytotoxicity results against A549 than MCF7, so that lung carcinoma cell line was chosen to perform the molecular studies on it. The results showed that all compounds (7, 8, 9 and 10) caused cell cycle arrest at G1 phase. The molecular docking study on CDK2 confirmed the results of cell cycle assay which showed good binding energy between the compounds and the active site of enzyme indicating the inhibition of the enzyme.

CARBON NANOHORN AS NANOCONTAINER FOR CISPLATIN: INSIGHTS ON THE INTERACTION WITH PLASMA MEMBRANES OF NORMAL AND BREAST CANCER CELLS

2021 ◽  
Author(s):  
Eduardo Ribeiro Almeida ◽  
Helio F. Dos Santos ◽  
Priscila V. S. Z. Capriles
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Plasma Membranes ◽  
Breast Cancer Treatment ◽  
Therapeutic Alternatives

Cisplatin (cddp)-based chemotherapy is one of the most effective therapeutic alternatives for breast cancer treatment, the most common form of cancer, despite the severe side effects related to the high...

Natural-Derived Molecules as a Potential Adjuvant in Chemotherapy: Normal Cell Protectors and Cancer Cell Sensitizers

2021 ◽  
Vol 21 ◽  
Author(s):  
Rajib Hossain ◽  
Muhammad Torequl Islam ◽  
Mohammad S. Mubarak ◽  
Divya Jain ◽  
Rasel Khan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Polyphenolic Compounds ◽  
Anticancer Effect ◽  
Anticancer Activities ◽  
Normal Cells ◽  
Anti Cancer ◽  
Global Threat

Background: Cancer is a global threat to humans and a leading cause of death worldwide. Cancer treatment includes, among other things, the use of chemotherapeutic agents, compounds that are vital for treating and preventing cancer. However, chemotherapeutic agents produce oxidative stress along with other side effects that would affect the human body. Objective: To reduce the oxidative stress of chemotherapeutic agents in cancer and normal cells by naturally derived compounds with anti-cancer properties, and protect normal cells from the oxidation process. Therefore, the need to develop more potent chemotherapeutics with fewer side effects has become increasingly important. Method: Recent literature dealing with the antioxidant and anticancer activities of the naturally naturally-derived compounds: morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin has been surveyed and examined in this review. For this, data were gathered from different search engines, including Google Scholar, ScienceDirect, PubMed, Scopus, Web of Science, Scopus, and Scifinder, among others. Additionally, several patient offices such as WIPO, CIPO, and USPTO were consulted to obtain published articles related to these compounds. Result: Numerous plants contain flavonoids and polyphenolic compounds such as morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin, which exhibit ‎antioxidant, anti-inflammatory, and anti-carcinogenic actions via several mechanisms. These compounds show sensitizers of cancer cells and protectors of healthy cells. Moreover, these compounds can reduce oxidative stress, which is accelerated by chemotherapeutics and exhibit a potent anticancer effect on cancer cells. Conclusions: Based on these findings, more research is recommended to explore and evaluate such flavonoids and polyphenolic compounds.

scholarly journals AWARENESS OF CHEMOTHERAPY SIDE EFFECTS AND ATTITUDE TOWARDS CHEMOTHERAPY USE AMONG CANCER PATIENTS ATTENDING ONCOLOGY CLINIC AT BUGANDO MEDICAL CENTRE, IN MWANZA, NORTHERN TANZANIA

2018 ◽  
Vol 8 (5) ◽  
pp. 448-454 ◽  
Author(s):  
Deogratias M Katabalo ◽  
Raphael Matinde ◽  
Stanley Mwita ◽  
Karoli Marwa ◽  
Nestory Masalu
Keyword(s):  
Side Effects ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cross Section ◽  
Positive Attitude ◽  
Medical Centre ◽  
Bugando Medical ◽  
Northern Tanzania ◽  
Chemotherapy Side Effects ◽  
Bugando Medical Centre

Background: Chemotherapy is the use of drugs to kill cancer cells. Because cancer cells generally grow and divide faster than normal cells, they are more susceptible to the action of these drugs. However, damage to healthy cells is unavoidable, and this damage accounts for the side effects linked to these drugs. Methodology: A cross section study was conducted at oncology department in Bugando Medical Centre. A sample of 216 people was recruited into the study. The data was collected by using the pre-constructed questionnaire. After data collection, the data was transferred into SPSS version 20 and analyzed. Results: The study found that 88 (40.7%) of the respondents were aware of the chemotherapy side effects whereby majority, 68 (77.3%) of these had been informed by the doctor. Most of the respondents, 197 (92.1%) had a positive attitude towards the use of chemotherapy. Conclusion: There is still poor awareness of the chemotherapy side effects among the cancer patients attending and receiving chemotherapy in oncology department at Bugando Medical Centre. However, most of the respondents had positive attitude towards the use of chemotherapy Keywords: Awareness, attitude, chemotherapy, side effects and Tanzania.

scholarly journals PENGARUH AKUPUNKTUR JIN’S 3 NEEDLE TERHADAP PENURUNAN INTENSITAS NYERI DIABETIC NEUROPATHY PERIFER

2020 ◽  
Vol 4 (1) ◽  
pp. 46-51
Author(s):  
Leny Candra Kurniawan ◽  
Ikhwan Abdullah
Keyword(s):  
Peripheral Neuropathy ◽  
Side Effects ◽  
Diabetic Neuropathy ◽  
Diabetic Peripheral Neuropathy ◽  
Nerve Fibers ◽  
Significance Level ◽  
Peripheral Diabetic Neuropathy ◽  
Study Population ◽  
Sugar Levels ◽  
Needle Acupuncture

Diabetic Peripheral Neuropathy is a type of nerve damagethat occurs due to diabetes. High blood sugar levels in thelong term can cause damage to nerve fibers throughout thebody, such as legs, feet, blood circulation, heart, digestivesystem, and urinary tract. Diabetic Peripheral Neuropathy isa serious complication of diabetes that often causes pain inthe limbs. Pain management Diabetic Peripheral Neuropathyis usually by administering pain medication for a long periodof time. These medicines will have side effects. The use ofacupuncture as an alternative to help reduce the intensity ofpain in peripheral diabetic neuropathy has proven to beeffective and relatively without side effects. The advantage ofacupuncture therapy is that it has relatively no side effects.The general aim of this study is to reduce the intensity of painin peripheral neuropathy. The research design usesquantitative methods. The study population was all patientswith peripheral neuropathy who visited the Harmoni HealthyClinic in March-May 2019. The sampling method used wasaccidental sampling. The benefits of this study provide analternative for DM sufferers to reduce the intensity ofneuropathic pain naturally with acupuncture without fear.side effects. From the results of this study it is known thatthere is an influence of Jin’s Three Needle acupuncture inreducing the intensity of pain in Peripheral Neuropathy.Calculations using statistical SPSS 21 with paired sample ttest obtained significant results (0.00) from the value of α(0.05), then H1 is accepted. So with a significance level of5%, it can be concluded that Jin's Three Needle acupuncturecan reduce the intensity of pain in diabetic peripheralneuropathy

scholarly journals The war against cancer: Suicide gene therapy

2016 ◽  
Vol 2 (3) ◽  
pp. 139
Author(s):  
Muzeyyen Izmirli ◽  
Dilara Sonmez ◽  
Bulent Gogebakan
Keyword(s):  
Gene Therapy ◽  
Cytochrome P450 ◽  
Side Effects ◽  
Cancer Cells ◽  
Thymidine Kinase ◽  
Viral Vectors ◽  
Suicide Gene ◽  
Suicide Gene Therapy ◽  
Kinase Gene ◽  
Cancer Society

<p>The National Cancer Institute and the American Cancer Society announced that 1.6 million new cancer cases are projected to occur in the USA in 2016. One of the most innovative approaches against cancer is suicide gene therapy, in which suicide-inducing transgenes are introduced into cancer cells. When cancer treatments target the total elimination of tumor cells, there will be no side effects for normal cells. Cancer tissues are targeted through various targeted transport methods, followed by tissue-specific enzymes converting a systemically suitable prodrug into an active drug in the tumor. Suicidal genes are delivered by transporters, such as viral and non-viral vectors, into cancer cells. Suicide gene therapeutic strategies currently pursued are herpes simplex virus thymidine kinase gene with prodrug ganciclovir, cytosine deaminase gene, carboxyl esterase/irinotecan, varicella zoster virus thymidine kinase/6-methoxypurine arabinonucleoside, nitroreductase Nfsb/5-(aziridin-1-yl)-2,4-dinitrobenzamide, carboxypeptidase G2/4-[(2-chloroethyl)(2- mesyloxyethyl)amino]benzoyl-L-glutamic acid, cytochrome p450-isofosfamide, and cytochrome p450-cyclophosphamide. The goal of this review is to summarize the different suicide gene systems and gene delivery vectors addressed to cancer cells, with a particular emphasis on recently developed systems. Finally, we briefly describe the advantageous clinical applications and potential side effects of suicide gene therapy. </p>

scholarly journals Chronic inflammatory demyelinating polyradiculoneuropathy induced by paclitaxel

2021 ◽  
Author(s):  
Isabella Sabião Borges ◽  
João Victor Aguiar Moreira ◽  
Eustaquio Costa Damasceno Junior ◽  
Alencar Pereira dos Santos ◽  
Gabriela Tomás Alves ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Glial Cells ◽  
Conduction Block ◽  
Chemotherapeutic Agents ◽  
Chronic Inflammatory Demyelinating Polyradiculoneuropathy ◽  
Microtubule Stabilization ◽  
Progressive Muscle Weakness ◽  
History Of ◽  
Secondary Demyelination ◽  
Distal Axonal Degeneration

Background: Peripheral neuropathies in cancer are most often due to neurotoxic chemotherapeutic agents. Approximately 30% of patients receiving neurotoxic chemotherapy (CTX) will suffer from chemotherapy-induced peripheral neuropathy (CIPN). Paclitaxel is an extremely effective chemotherapeutic agent for the treatment of breast, ovarian, and lung cancer. However, paclitaxel-induced peripheral neuropathy occurs in 59-87% of patients who receive this drug. Paclitaxel is an anti-tubulin drug that causes microtubule stabilization, resulting in distal axonal degeneration, secondary demyelination and nerve fiber loss. Case: We present a case of a 68-year-old female patient with history of breast cancer who presented sensorial ataxia and progressive muscle weakness two months after starting CTX with paclitaxel. The physical examination showed tetraparesis with proximal predominance, areflexia, severe hypopalesthesia and postural instability. Electroneuromyography showed the existence of asymmetric demyelinating polyradiculoneuropathy, with conduction block and temporal dispersion in practically all evaluated nerves. The cerebrospinal fluid confirmed the albumin-cytological dissociation. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was confirmed and patient underwent monthly treatment with methylprednisolone with good response. Discussion: Evidences has implicated neuroinflammation in the development of PIPN. While most CTX drugs do not cross the blood-brain-barrier, they readily penetrate the blood-nerve-barrier and bind to and accumulate in dorsal root ganglia and peripheral axons. CTX can induce neuroinflammation through activation of immune and immune- like glial cells. In fact, immune cells (e.g., macrophages, lymphocytes) and glial cells (e.g., Schwann cells) in the peripheral nervous system play important role in the induction and maintenance of neuropathy. Conclusion: CIDP should be included in the spectrum of CIPN.

scholarly journals A Novel Marine Natural Product Derived Pyrroloiminoquinone with Potent Activity against Skin Cancer Cells

Marine Drugs ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. 443 ◽  
Author(s):  
Jaden Cowan ◽  
Mohammad Shadab ◽  
Dwayaja H. Nadkarni ◽  
Kailash KC ◽  
Sadanandan E. Velu ◽  
...  
Keyword(s):  
Natural Products ◽  
Side Effects ◽  
Skin Cancer ◽  
Cancer Cells ◽  
Natural Product ◽  
The United States ◽  
Marine Natural Product ◽  
Migration And Invasion ◽  
Migration Assay ◽  
Lead Compounds

Non-melanoma skin cancer is one of the major ailments in the United States. Effective drugs that can cure skin cancers are limited. Moreover, the available drugs have toxic side effects. Therefore, skin cancer drugs with less toxic side effects are urgently needed. To achieve this goal, we focused our work on identifying potent lead compounds from marine natural products. Five lead compounds identified from a class of pyrroloiminoquinone natural products were evaluated for their ability to selectively kill squamous cell carcinoma (SCC13) skin cancer cells using an MTT assay. The toxicity of these compounds was also evaluated against the normal human keratinocyte HaCaT cell line. The most potent compound identified from these studies, C278 was further evaluated for its ability to inhibit cancer cell migration and invasion using a wound-healing assay and a trans-well migration assay, respectively. To investigate the molecular mechanism of cell death, the expression of apoptotic and autophagy proteins was studied in C278 treated cells compared to untreated cells using western blot. Our results showed that all five compounds effectively killed the SCC13 cells, with compound C278 being the most effective. Compound C278 was more effective in killing the SCC13 cells compared to HaCaT cells with a two-fold selectivity. The migration and the invasion of the SCC13 cells were also inhibited upon treatment with compound C278. The expression of pro-apoptotic and autophagy proteins with concomitant downregulation in the expression of survival proteins were observed in C278 treated cells. In summary, the marine natural product analog compound C278 showed promising anticancer activity against human skin cancer cells and holds potential to be developed as an effective anticancer agent to combat skin cancer.

Sign in / Sign up

Export Citation Format

Share Document