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Fulltext Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity

Voon YL, Ahmad M, Wong PF, Husaini R, Ng WT, Leong CO, et al.

Oncol Rep, 2015 Oct;34(4):1692-700.
PMID: 26252575 DOI: 10.3892/or.2015.4177

The small-molecule inhibitor of p53-Mdm2 interaction, Nutlin-3, is known to be effective against cancers expressing wild-type (wt) p53. p53 mutations are rare in nasopharyngeal carcinoma (NPC), hence targeting disruption of p53-Mdm2 interaction to reactivate p53 may offer a promising therapeutic strategy for NPC. In the present study, the effects of Nutlin-3 alone or in combination with cisplatin, a standard chemotherapeutic agent, were tested on C666-1 cells, an Epstein-Barr virus (EBV)-positive NPC cell line bearing wt p53. Treatment with Nutlin-3 activated the p53 pathway and sensitized NPC cells to the cytotoxic effects of cisplatin. The combined treatment also markedly suppressed soft agar colony growth formation and increased apoptosis of NPC cells. The effect of Nutlin-3 on NPC cells was inhibited by knockdown of p53, suggesting that its effect was p53-dependent. Extended treatment with increasing concentrations of Nutlin-3 did not result in emergence of p53 mutations in the C666-1 cells. Collectively, the present study revealed supportive evidence of the effectiveness of combining cisplatin and Nutlin-3 as a potential therapy against NPC.

Matched MeSH terms: Cisplatin/administration & dosage
Fulltext Epithelial-to-mesenchymal transition (EMT) to sarcoma in recurrent lung adenosquamous carcinoma following adjuvant chemotherapy

Poh ME, Liam CK, Mun KS, Chai CS, Wong CK, Tan JL, et al.

Thorac Cancer, 2019 09;10(9):1841-1845.
PMID: 31350945 DOI: 10.1111/1759-7714.13156

Adjuvant chemotherapy has long been indicated to extend survival in completely resected stage IB to IIIA non-small cell lung cancer (NSCLC). However, there is accumulating evidence that chemotherapy or chemoradiotherapy can induce epithelial-to-mesenchymal transition (EMT) in disseminated or circulating NSCLC cells. Here, we describe the first case of EMT as the cause of recurrence and metastasis in a patient with resected stage IIB lung adenosquamous carcinoma after adjuvant chemotherapy. We review the literature and explore the possible mechanisms by which EMT occurs in disseminated tumor cells (DTC) or circulating tumor cells (CTC) in response to adjuvant chemotherapy (cisplatin) as a stressor. We also explore the possible therapeutic strategies to reverse EMT in patients with recurrence. In summary, although adjuvant cisplatin-based chemotherapy in resected NSCLC does extend survival, it may lead to the adverse phenomenon of EMT in disseminated tumor cells (DTC) or circulating tumor cells (CTC) causing recurrence and metastasis.

Matched MeSH terms: Cisplatin/administration & dosage
Myasthenia gravis and a rare complication of chemotherapy

Ng CV

Med J Aust, 2005 Feb 07;182(3):120.
PMID: 15698357

We describe a patient with myasthenia gravis and thymoma who developed recurrent severe myasthenic crises associated with the use of combination chemotherapy.

Matched MeSH terms: Cisplatin/administration & dosage
Fulltext Induction of Apoptosis and Cytotoxicity by Isothiocyanate Sulforaphene in Human Hepatocarcinoma HepG2 Cells

Kntayya SB, Ibrahim MD, Mohd Ain N, Iori R, Ioannides C, Abdull Razis AF

Nutrients, 2018 Jun 04;10(6).
PMID: 29866995 DOI: 10.3390/nu10060718

Glucoraphenin, a glucosinolate present in large quantities in radish is hydrolysed by myrosinase to form the isothiocyanate sulforaphene, which is believed to be responsible for its chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aim of the study is to assess the cytotoxicity of sulforaphene in HepG2 cells and evaluate its potential to enhance apoptosis. The cytotoxicity of sulforaphene in HepG2 cells was carried out ensuing an initial screening with two other cell lines, MFC-7 and HT-29, where sulforaphene displayed highest toxicity in HepG2 cells following incubation at 24, 48 and 72 h. In contrast, the intact glucosinolate showed no cytotoxicity. Morphological studies indicated that sulforaphene stimulated apoptosis as exemplified by cell shrinkage, blebbing, chromatin condensation, and nuclear fragmentation. The Annexin V assay revealed significant increases in apoptosis and the same treatment increased the activity of caspases -3/7 and -9, whereas a decline in caspase-8 was observed. Impairment of cell proliferation was indicated by cell cycle arrest at the Sub G₀/G₁ phase as compared to the other phases. It may be concluded that sulforaphene, but not its parent glucosinolate, glucoraphenin, causes cytotoxicity and stimulates apoptosis in HepG2 cells.

Matched MeSH terms: Cisplatin/pharmacology
Fulltext Multi-Target Approach to Metastatic Adrenal Cell Carcinoma

Wahab NA, Zainudin S, AbAziz A, Mustafa N, Sukor N, Kamaruddin NA

Arch Iran Med, 2016 Sep;19(9):671-3.
PMID: 27631184 DOI: 0161909/AIM.0012

Adrenal cell carcinoma is a rare tumor and more than 70% of patients present with advanced stages. Adrenal cell carcinoma is an aggressive tumor with a poor prognosis. Surgical intervention is the gold standard treatment and mitotane is the only drug approved for the treatment of adrenal cell carcinoma. Until recently in 2012, the etoposide, doxorubicin, cisplatin plus mitotane are approved as first-line therapy based on response rate and progression-free survival. This case illustrates a case of advanced adrenal cell carcinoma in a young girl who presented with huge adrenal mass with inferior vena cava thrombosis and pulmonary embolism. Multi-approach of therapy was used to control the tumor size and metastasis. Therefore, it may prolong her survival rate for up to 5 years and 4 months.

Matched MeSH terms: Cisplatin/administration & dosage
Fulltext Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In Vivo

Mohamad NE, Abu N, Yeap SK, Alitheen NB

Integr Cancer Ther, 2019 11 23;18:1534735419880258.
PMID: 31752555 DOI: 10.1177/1534735419880258

Background: This study aimed to evaluate the antitumor enhancing effect of bromelain consumption on 4T1-challenged mice treated with cisplatin. Methods: Mice challenged with 4T1 triple-negative breast cancer cells received water, bromelain, cisplatin, or bromelain + cisplatin treatment for 28 days. Tumor size was measured, and lung metastasis was evaluated by clonogenic assay. Expression of tumor inflammatory genes of the harvested tumor was quantified by polymerase chain reaction array and ELISA (enzyme-linked immunosorbent assay). Results: All treatments significantly reduced the size of tumor and lung metastasis, with combination treatment showing the best effect. Also, bromelain alone and combination treatment showed downregulation of the expression of tumor inflammatory genes (Gremlin [GREM1], interleukin 1β [IL-1β], interleukin-4 [IL-4], nuclear factor κB subunit 1 [NFκB1], and prostaglandin-endoperoxide synthase 2 [PTGS2]), tumor nitric oxide level, and serum IL-1β, and IL-4 levels. On the other hand, cisplatin treatment increased the expression of selected inflammatory markers. Conclusion: This study suggests that bromelain treatment could potentiate the antitumor effect of cisplatin on triple-negative breast cancer 4T1 cells through modulating the tumor environmental inflammation.

Matched MeSH terms: Cisplatin/pharmacology*
Long-term survival of nasopharyngeal carcinoma patients treated with adjuvant chemotherapy subsequent to conventional radical radiotherapy

Prasad U, Wahid MI, Jalaludin MA, Abdullah BJ, Paramsothy M, Abdul-Kareem S

Int J Radiat Oncol Biol Phys, 2002 Jul 1;53(3):648-55.
PMID: 12062608

To assess the long-term survival of patients with nasopharyngeal carcinoma (NPC) who were treated with conventional radical radiotherapy (RT) followed by adjuvant chemotherapy.

Matched MeSH terms: Cisplatin/administration & dosage
Fulltext Radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for N2-3 nasopharyngeal cancer: a multicenter trial of the Forum for Nuclear Cooperation in Asia

Ohno T, Thinh DH, Kato S, Devi CR, Tung NT, Thephamongkhol K, et al.

J Radiat Res, 2013 May;54(3):467-73.
PMID: 23192700 DOI: 10.1093/jrr/rrs115

The purpose of this study was to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for the treatment of N2-3 nasopharyngeal cancer (NPC) in Asian countries, especially regions of South and Southeast Asian countries where NPC is endemic. Between 2005 and 2009, 121 patients with NPC (T1-4 N2-3 M0) were registered from Vietnam, Malaysia, Indonesia, Thailand, The Philippines, China and Bangladesh. Patients were treated with 2D radiotherapy concurrently with weekly cisplatin (30 mg/m (2)), followed by adjuvant chemotherapy, consisting of cisplatin (80 mg/m(2) on Day 1) and fluorouracil (800 mg/m(2) on Days 1-5) for 3 cycles. Of the 121 patients, 56 patients (46%) required interruption of RT. The reasons for interruption of RT were acute non-hematological toxicities such as mucositis, pain and dermatitis in 35 patients, hematological toxicities in 11 patients, machine break-down in 3 patients, poor general condition in 2 patients, and others in 8 patients. Of the patients, 93% completed at least 4 cycles of weekly cisplatin during radiotherapy, and 82% completed at least 2 cycles of adjuvant chemotherapy. With a median follow-up time of 46 months for the surviving 77 patients, the 3-year locoregional control, distant metastasis-free survival and overall survival rates were 89%, 74% and 66%, respectively. No treatment-related deaths occurred. Grade 3-4 toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of the patients, respectively. In conclusion, further improvement in survival and locoregional control is necessary, although our regimen showed acceptable toxicities.

Matched MeSH terms: Cisplatin/administration & dosage*
Fulltext Vitamin E (α-Tocopherol) Exhibits Antitumour Activity on Oral Squamous Carcinoma Cells ORL-48

Zulkapli R, Abdul Razak F, Zain RB

Integr Cancer Ther, 2017 09;16(3):414-425.
PMID: 28818030 DOI: 10.1177/1534735416675950

Cancers involving the oral cavity, head, and neck regions are often treated with cisplatin. In cancer therapy, the main target is to eliminate unwanted cancerous cells. However, reports on the nonselective nature of this drug have raised few concerns. Incorrect nutritional habits and lifestyle practices have been directly linked to cancer incidence. Nutrients with antioxidant activity inhibit cancer cells development, destroying them through oxidative stress and apoptosis. α-tocopherol, the potent antioxidant form of vitamin E is a known scavenger of free radicals. In vitro study exhibited effective antitumor activity of α-tocopherol on ORL-48 at 2.5 ± 0.42 µg/mL. Cisplatin exhibited stronger activity at 1.0 ± 0.15 µg/mL, but unlike α-tocopherol it exhibited cytotoxicity on normal human epidermal keratinocytes at very low concentration (<0.1 µg/mL). Despite the lower potency of α-tocopherol, signs of apoptosis such as the shrinkage of cells and appearance of apoptotic bodies were observed much earlier than cisplatin in time lapse microscopy. No apoptotic vesicles were formed with cisplatin, instead an increased population of cells in the holoclone form which may suggest different induction mechanisms between both agents. High accumulation of cells in the G0/G1 phase were observed through TUNEL and annexin V-biotin assays, while the exhibition of ultrastructural changes of the cellular structures verified the apoptotic mode of cell death by both agents. Both cisplatin and α-tocopherol displayed cell cycle arrest at the Sub G0 phase. α-tocopherol thus, showed potential as an antitumour agent for the treatment of oral cancer and merits further research.

Matched MeSH terms: Cisplatin/pharmacology
Urinary metabolic profiling of cisplatin nephrotoxicity and nephroprotective effects of Orthosiphon stamineus leaves elucidated by 1H NMR spectroscopy

Pariyani R, Ismail IS, Azam A, Khatib A, Abas F, Shaari K, et al.

J Pharm Biomed Anal, 2017 Feb 20;135:20-30.
PMID: 27987392 DOI: 10.1016/j.jpba.2016.12.010

Orthosiphon stamineus (OS) is a popular medicinal herb used in traditional Chinese medicine as a diuretic agent and for renal system disorders. This study employed 1H NMR based metabolomics approach to investigate the possible protective activity of OS in cisplatin induced nephrotoxicity owing to its diuretic and antioxidant activities. Aqueous (OSAE) and 50% aqueous ethanolic (OSFE) extracts of OS leaves were orally administered at 400mg/kg BW doses to rats which were then intraperitoneally injected with cisplatin at 5mg/kg BW dose. The 1H NMR profile of the urine samples collected on day 5 after cisplatin administration were analyzed by multivariate pattern recognition techniques, whereby 19 marker metabolites suggestive in the involvement of TCA cycle, disturbed energy metabolism, altered gut microflora and BCAA metabolism pathways were identified. It was observed that OSFE caused significant changes (p<0.05) in the levels of 8 markers namely leucine, acetate, hippurate, lysine, valine, 2-oxoglutarate, 3-HBT and acetoacetate resulting in a moderate ameliorative effect, however, it did not completely protect from nephrotoxicity. OSAE did not demonstrate significant down regulatory effects on any markers, albeit, it potentiated the cisplatin nephrotoxicity by inducing significant increase in glucose, glycine, creatinine, citrate, TMAO, acetate and creatine levels. A Principal Component Analysis (PCA) of the 1H NMR spectra of OS extracts identified that OSFE had higher concentrations of the secondary metabolites such as caffeic acid, chlorogenic acid, protocatechuic acid and orthosiphol, among others. Whereas, OSAE was characterized by higher concentrations of acetate, lactate, succinic acid, valine and phosphatidylcholine. This research denotes the first comprehensive analysis to identify the effects of OS extracts on cisplatin nephrotoxicity.

Matched MeSH terms: Cisplatin/toxicity*
Fulltext Preliminary experience with mitomycin, vinblastine and cisplatin (MVP) combination chemotherapy in the treatment of advanced non-small cell lung cancer at University Hospital, Kuala Lumpur

Lee SM

Singapore Med J, 1990 Jun;31(3):228-32.
PMID: 2168091

Twelve patients with advanced inoperable non-small cell lung cancer (NSCLC) were treated with mitomycin, vinblastine and cisplatin (MVP) combination chemotherapy. The overall response rate was 33% (4 partial responses and no complete response) with a median survival of seven months. One responder above subsequently achieved complete remission following successful resection of his tumour and is still alive 14 months after initial chemotherapy. Responses were observed in patients with good performance status and limited disease. Side-effects were generally well tolerated and manageable. MVP is an effective regimen and the low response rate achieved here as compared to other centres is also discussed.

Matched MeSH terms: Cisplatin/therapeutic use
Synthesis, characterization and anti-cancer properties of water-soluble bis(PYE) pro-ligands and derived palladium(ii) complexes

Zafar MN, Masood S, Chaudhry GE, Muhammad TST, Dalebrook AF, Nazar MF, et al.

Dalton Trans, 2019 Aug 08.
PMID: 31393494 DOI: 10.1039/c9dt01923e

The two cationic palladium(ii) complexes, [Pd(Len)2][OTf]2 (4) and [Pd(Lphen)2][OTf]2 (5), were synthesized by treatment of bis(benzonitrile)dichloropalladium(ii) with [H2Len][OTf]2 (2) or [H2Lphen][OTf]2 (3), respectively, in the presence of a weak base. The pro-ligands 2 and 3 were synthesized by melt reactions between N-methyl-4-chloropyridinium triflate (1) and the amines ethylenediamine or phenylenediamine, respectively. The water-soluble compounds 2-5 were fully characterized, including by single-crystal X-ray crystal structure determinations for 2-4. UV-Vis and fluorescence spectroscopy were used to study the binding interactions of 2-5 with CT-DNA. The spectroscopic data suggested the presence of intercalative and groove binding modes and this was supported by molecular docking studies. The in vitro cytotoxicity studies (IC50 values) showed that the human breast cancer cell lines MCF-7 and T47D were more sensitive towards 3, 4 and 5 than cisplatin. The cytotoxicity of the new compounds decreased in the order 5 > 4 > 3 > 2. Furthermore, the annexin V-FITC staining method strongly suggested the presence of phosphatidylserine (PS) on the outer membrane of the treated cells, which is a hallmark of apoptosis.

Matched MeSH terms: Cisplatin
Polygonum minus essential oil modulates cisplatin-induced hepatotoxicity through inflammatory and apoptotic pathways

Abd Rashid N, Hussan F, Hamid A, Adib Ridzuan NR, Halim SASA, Abdul Jalil NA, et al.

EXCLI J, 2020;19:1246-1265.
PMID: 33122975 DOI: 10.17179/excli2020-2355

Oxidative stress, inflammation and apoptosis are thought as primary mediators of cisplatin-induced hepatotoxicity. The objective of this study was to determine the protective effect of Polygonum minus essential oil in cisplatin-induced hepatotoxicity. A total of forty-two male rats were randomly divided into seven groups: control, cisplatin, β-caryophyllene 150 mg/kg (BCP), PmEO 100 mg/kg + cisplatin (PmEO100CP), PmEO 200 mg/kg + cisplatin (PmEO200CP), PmEO 400 mg/kg + cisplatin (PmEO400CP) and PmEO 400 mg/kg (PmEO400). Rats in the BCP, PmEO100CP, PmEO200CP, PmEO400CP and PmEO400 group received respective treatment orally for 14 consecutive days prior to cisplatin injection. All animals except for those in the control group and PmEO400 were administered with a single dose of cisplatin (10 mg/kg) intraperitoneally on day 15 and all animals were sacrificed on day 18. PmEO100CP pretreatment protected against cisplatin-induced hepatotoxicity by decreasing CYP2E1 and indicators of oxidative stress including malondialdehyde, 8-OHdG and protein carbonyl which was accompanied by increased antioxidant status (glutathione, glutathione peroxidase, superoxide dismutase and catalase) as compared to cisplatin group. PmEO100CP pretreatment also modulated changes in liver inflammatory markers (TNF-α, IL-1α, IL-1β, IL-6 and IL-10). PmEO100CP administration also notably reduced cisplatin-induced apoptosis significantly as compared to cisplatin group. In conclusion, our results suggested that P. minus essential oil at a dose of 100 mg/kg may protect against cisplatin-induced hepatotoxicity possibly via inhibition of oxidative stress, inflammation and apoptosis.

Matched MeSH terms: Cisplatin
Fulltext Effective Dose Estimation of Patients Administered with 18F-FDG and Ga-68 DOTATATE in PET/CT Examination Associated with Gender and Weight

Kamal, I., Said, M. A., Bathumalai, J., Abdul Razak, H. R., Abdul Karim, M. K.

Physics and Technology in Medicine, 2020;1(1):15-21.
MyJurnal

The whole-body fluorodeoxyglucose F18 (18F-FDG) and gallium-68 (Ga-68 DOTATATE) are the most common radiopharmaceutical use in PET/CT imaging for cancer staging. Although radiopharmaceutical for PET/CT examination has been acknowledged for its safety and efficacy, the internal dosimetry and effective dose (ED) from the examinations are rarely discussed. Hence, this study aimed to evaluate radiation ED for whole-body radiopharmaceuticals PET/CT concerning patients’ gender and their weight. A total of 82 oncology patients (44 males and 38 females) were collected retrospectively from Institut Kanser Negara, Putrajaya. Data, such as 18F-FDG and Ga-68 DOTATATE activity and patient demography (weight, height, age), were recorded and analyzed. Effective doses from both internal and external exposure were calculated using the coefficient
provided by the International Commission on Radiological Protection (ICRP) report. The total ED of 18F-FDG for male patients was 20.2 ± 8.6 mSv and for female patients were 19.0 ± 8.2 mSv while total whole-body ED for Ga-68 DOTATATE for male patients was 18.5 ± 7.0 mSv and 17.0 ± 5.6 mSv for female patients. The ratio for ED between male and female were 1:1 for both examinations ranged from 12.0 – 23 mSv. From this study, it indicated that the ED of Ga-68 DOTATATE was far lower when compared to the ED of 18F-FDG by a factor of 0.7. Therefore, it is crucial to optimize the PET/CT protocol dose in order to uphold the dose as low as reasonably achievable (ALARA).

Matched MeSH terms: Cisplatin
Fulltext Standardization and experience may influence the survival of laparoscopic radical hysterectomy for cervical cancer

Lee CL, Huang KG, Chua PT, Mendoza MCVR, Lee PS, Lai SY

Taiwan J Obstet Gynecol, 2021 May;60(3):463-467.
PMID: 33966729 DOI: 10.1016/j.tjog.2021.03.013

OBJECTIVE: Minimally invasive radical hysterectomy has been shown to be associated with poorer outcome in an influential prospective, randomized trial. However, many centers worldwide performing minimally invasive radical hysterectomy have data and experience that prove otherwise. We aim to review surgical and oncologic outcomes of patients operated by Laparoscopic Radical Hysterectomy in a tertiary hospital, by experienced surgeons and standardization in radicality, for cervical carcinoma Stage 1A1-1B1 from January 2009 to May 2014.
MATERIALS & METHODS: Standardised surgical technique with Parametrium & Paracolpium resection approach was adopted by qualified and experienced Gynecologic/Gyne-Oncologic Endoscopic & Minimally Invasive Surgeons in performing Laparoscopic Radical Hysterectomy for Cervical Cancer stage 1A1-1B1 from January 2009-May 2014, involving 53 patients. Electronic Medical Record system (EMR) Of Chang Gung Memorial Hospital(Tertiary Referral Centre), Department of Obstetrics & Gynecology was accessed for surgical and oncologic outcomes.
RESULTS: Fifty-Three patients operated from January 2009 to May 2014 were followed up for an average of 96.7 months with longest follow-up at 127 months. There were no cases of recurrence or death reported. 5 Year - Survival Rate and 5 Year Disease-Free Survival Rate were 100%. Two patients received post-operative pelvic radiation concurrent with chemotherapy using Cisplatin due to greater than 1/3 cervical stromal invasion.
CONCLUSION: It is vital to standardize minimally invasive surgical techniques for early stage cervical cancer, with focus on adequate radicality and resection which may contribute to excellent survival outcomes. Further international multi-center randomized trial (Minimally Invasive Therapy Versus Open Radical Hysterectomy In Cervical Cancer) will provide justification for continued practice of MIS in early stage cervical cancer.

Matched MeSH terms: Cisplatin
Phenotypic and microRNA characterisation of the neglected CD24+ cell population in MCF-7 breast cancer 3D spheroid culture

Boo L, Yeap SK, Ali NM, Ho WY, Ky H, Satharasinghe DA, et al.

J Chin Med Assoc, 2019 Nov 15.
PMID: 31770189 DOI: 10.1097/JCMA.0000000000000226

BACKGROUND: In vitro 3-dimensional spheroid culture has been widely used as model to enrich CD44CD24 cancer stem cells (CSC) with high ALDH1 activity. Although CD24subpopulation was known to be present in 3D spheroids and may influence cancer drug therapies, its characteristics and CSC properties were not well defined.
METHODS: In this study, CD24 population from the MCF-7 spheroid was sorted and subjected to spheroid formation test, stem cell markers immunofluorescence, invasion and migration test as well as microRNA expression profiling.
RESULTS: Sorted MCF-7 CD24 cells from primary spheroids were able to reform its 3D spheroid shape after 7 days in non-adherent culture conditions. In contrast to the primary spheroids, the expression of SOX-2, CD44, CD49f and Nanog were dim in MCF-7 CD24+ cells. Remarkably, MCF-7 CD24 cells were found to show high expression of ALDH1 protein which may have resulted in these cells exhibiting higher resistance against doxorubicin and cisplatin when compared to that of the parental cells. Moreover, microRNA profiling has shown that the absence of cancer stem cell properties were consistent with the downregulation of major cancer stem cells related pathways including Hedgehog, Wnt and MAPK signalling pathways. However, the upregulated pathways such as adherans junctions, focal adhesion and tight junction suggest that CD24+ cells were probably at an epithelial-like state of cell transition.
CONCLUSION: In conclusion, neglected CD24+ cells in MCF-7 spheroid did not exhibit typical breast CSCs properties. The presence of miRNAs and their analysed pathways suggested that these cells could be a distinct intermediate cell state in breast CSCs.

Matched MeSH terms: Cisplatin
Fulltext Vernonia cinerea regenerates tubular epithelial cells in cisplatin induced nephrotoxicity in cancer bearing mice without affecting antitumor activity

Amuthan A, Devi V, Shreedhara CS, Rao V, Jasphin S, Kumar N

J Tradit Complement Med, 2021 May;11(3):279-286.
PMID: 34012874 DOI: 10.1016/j.jtcme.2020.08.004

Background: Traditional Siddha Medicine advises using metal-based formulations to treat cancers. In the case of any toxicities during the therapy, Siddha physicians use Vernonia cinerea (VC) whole plant kashayam (crude aqueous extract-CAE) to reverse the toxic effects.
Aim: To evaluate the nephroprotective activity of CAE and its fractions in cisplatin-induced nephrotoxicity and to assess whether they compromise the anticancer efficacy of cisplatin.
Materials and methods: Cisplatin-induced renal damage was induced in Ehrlich Ascites Carcinoma (EAC) bearing mice during mild phase of tumor growth. CAE and its butanol (BF) and aqueous (AF) fractions were administered orally from the 5th day for five days. Nephroprotective potential (serum urea, creatinine, renal histology) and effect of VC on cisplatin anticancer efficacy (tumor volume, viable tumor cells, percentage increase in life span (% ILS)) were calculated.
Result: CAE and its fractions significantly reversed the cisplatin-induced renal damage. CAE and BF treated animals showed regeneration of 50%-75% of proximal tubular cells. Compared to EAC control mice, the % ILS of the cisplatin-treated group was 244% and it was further extended to 379% after CAE administration. The % ILS in the CAE treated group was 1.6 times higher than the cisplatin alone treated group. GC-MS study showed the presence of astaxanthin and betulin.
Conclusion: CAE of VC reverses cisplatin-induced kidney damage as well as regenerates proximal tubular epithelial cells, without compromising the anticancer effect of cisplatin. When CAE was further fractionated, the nephroprotective activity was retained, but the beneficial anticancer effect of cisplatin was compromised.

Matched MeSH terms: Cisplatin
Recent advances and prospects in gemcitabine drug delivery systems

Paroha S, Verma J, Dubey RD, Dewangan RP, Molugulu N, Bapat RA, et al.

Int J Pharm, 2021 Jan 05;592:120043.
PMID: 33152476 DOI: 10.1016/j.ijpharm.2020.120043

Cancer is a community health hazard which progress at a fatal rate in various countries across the globe. An agent used for chemotherapy should exhibit ideal properties to be an effective anticancer medicine. The chemotherapeutic medicines used for treatment of various cancers are, gemcitabine, paclitaxel, etoposide, methotrexate, cisplatin, doxorubicin and 5-fluorouracil. However, many of these agents present nonspecific systemic toxicity that prevents their treatment efficiency. Of all, gemcitabine has shown to be an active agent against colon, pancreatic, colon, ovarian, breast, head and neck and lung cancers in amalgamation with various anticancer agents. Gemcitabine is considered a gold-standard and the first FDA approved agent used as a monotherapy in management of advanced pancreatic cancers. However due to its poor pharmacokinetics, there is need of newer drug delivery system for efficient action. Nanotechnology has shown to be an emerging trend in field of medicine in providing novel modalities for cancer treatment. Various nanocarriers have the potential to deliver the drug at the desired site to obtain information about diagnosis and treatment of cancer. This review highlights on various nanocarriers like polymeric nanoparticles, solid lipid nanoparticles, mesoporous silica nanoparticles, magnetic nanoparticles, micelles, liposomes, dendrimers, gold nanoparticles and combination approaches for delivery of gemcitabine for cancer therapy. The co-encapsulation and concurrent delivery of Gem with other anticancer agents can enhance drug action at the cancer site with reduced side effects.

Matched MeSH terms: Cisplatin
NOTCH1 Signaling Regulates Self-renewal and Platinum Chemoresistance of Cancer Stem-like Cells in Human Non-small Cell Lung Cancer

Zhang Y, Xu W, Guo H, Zhang Y, He Y, Lee SH, et al.

Cancer Res, 2017 Apr 17.
PMID: 28416482 DOI: 10.1158/0008-5472.CAN-16-1633

Cancer stem-like cells (CSC) are thought to drive tumor initiation, metastasis, relapse and therapeutic resistance, but their specific pathogenic characters in many cancers including non-small cell lung cancer (NSCLC) have yet to be well defined. Here we develop findings that the growth factor HGF promotes CSC sphere formation in NSCLC cell populations. In patient-derived sphere-forming assays (PD-SFA) with HGF, CD49f and CD104 were defined as novel markers of lung CSC (LCSC). In particular, we isolated a subpopulation of CD166(+)CD49f(hi)CD104(-)Lin(-) LCSC present in all human specimens of NSCLC examined, regardless of their histological subtypes or genetic driver mutations. This specific cell population was tumorigenic and capable of self-renewal, giving rise to tumor spheres in vitro and orthotopic lung tumors in immune-compromised mice. Mechanistic investigations established that NOTCH1 was preferentially expressed in this cell subpopulation and required for self-renewal via the transcription factor HES1. Through a distinct HES1-independent pathway, NOTCH1 also protected LCSCs from cisplatin-induced cell death. Notably, treatment with a γ-secretase inhibitor that blunts NOTCH1 function ablated self-renewing LCSC activity and restored platinum sensitivity in vitro and in vivo Overall, our results define the pathogenic characters of a cancer stem-like subpopulation in lung cancer, the targeting of which may relieve platinum resistance in this disease.

Matched MeSH terms: Cisplatin
‘Emergency chemotherapy’ for bleeding cervical cancer: case series

Shafiee, M.N., NorAzlin, M.I., Lim, P.S., Arifuddin D, Trika I, Hatta, D.

Journal of Surgical Academia, 2012;2(2):35-37.
MyJurnal

Fulminant haemorrhage in cervical cancer leads to severe anaemia and haemodynamic instability. Palliative management includes vaginal packing as temporary measure, radiotherapy and other invasive surgical procedures. High dose emergency chemotherapy is not commonly implemented particularly when complicated with anaemia and renal impairment. We discuss three case series on the usefulness of high dose chemotherapy to combat bleeding from cervical cancer as an emergency treatment. The first case was clinically staged as operable 2A disease with severe anaemia due to bleeding from the tumour mass. The haemoglobin was corrected by blood transfusion while the bleeding was being arrested by high dose chemotherapy. The second case was inoperable with invasion to the bladder mucosa. She had frank haematuria and bleeding from the tumour with severe anaemia. A course of chemotherapy and blood transfusion controlled the bleeding and anaemia was corrected. The third case presented late with obstructive uropathy and anaemia. She required dialysis, blood transfusion and high dose emergency chemotherapy to stop the bleeding before undergoing urinary diversion after an unsuccessful ureteric stenting. High dose chemotherapy consisting cisplatin, vincristine, bleomycin and mitomycin-C has a clinical value in arresting fulminant haemorrhage in cervical cancer.

Matched MeSH terms: Cisplatin

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