Bioactive extract of mycelia biomass of Ganoderma lucidum protects doxorubicin induced cardiomyopathy

Cardiotoxicity induced by anticancer drug; doxorubicin (DOX) is a limiting factor for its prolonged use in chemotherapy. No effective drug is currently available to prevent DOX induced cardiomyopathy. Ganoderma lucidum is highly valued medicinal mushroom used in traditional medicine. Mycelia biomasses are considered as alternate sources of mushroom bioactive compounds. We examined the effect of bioactive extract of G. lucidum mycelia biomass (GLME) to prevent cardiotoxicity induced by DOX in rats using a cumulative dose 18 mg/kg body wt. GLME was administered to animals at doses of 250 and 500 mg/kg body wt. once daily for five days prior to DOX administration and continued for three more days. Animals were sacrificed 24 h after the last dose of drug. Activities of creatine kinase (CK), lactate dehydrogenase (LDH), endogenous antioxidant status, oxidative stress markers, electrocardiograph (ECG) and haematological parameters were evaluated. DOX administration drastically elevated CK, LDH, myocardial peroxidation and oxidative stress and significantly lowered endogenous antioxidant activity. GLME administration attenuated elevated levels of CK, LDH and oxidative stress and also ameliorated alterations in haematological and ECG parameters. Results revealed that bioactive extract of G. lucidum mycelia imparted significant protection against DOX induced cardiomyopathy suggesting the potential therapeutic significance of G. lucidum mycelia bioactives to alleviate DOX induced cardiomyopathy.

Expert consensus on the diagnosis and treatment of anticancer drug-induced interstitial lung disease / 中华肿瘤杂志

Drug-induced interstitial lung disease (DILD) is the most common pulmonary adverse events caused by anti-cancer treatment. In recent years, with the development of clinical oncology, a large amount of novel anti-cancer drugs have been approved and widely used in clinical practice, and the incidence of anti-cancer drug related DILD is gradually increasing. DILD lacks specific clinical manifestations or diagnostic criteria. If not treated properly, it may leads to interruption or discontinuation of anti-cancer treatment, or even become life threat in severe cases. Therefore, the Anti-cancer Drug-induced Interstitial Lung Disease Management Group have reached a consensus on the diagnosis and management of anti-cancer DILD after several rounds of discussion. This consensus aims to improve clinicians' awareness of anti-cancer drug related-DILD and proposes an algorithm for the diagnosis and treatment of this disease, and to improve patients' prognosis and quality of life.

Recent advancement in targeting the KRAS-G12C mutant for cancer therapy / 药学学报

RAS, as a well-known proto-oncogene, is the most frequently mutated oncogene in human cancers, yet tremendous efforts over the past 30 years have failed to develop effective therapies for RAS-mutant cancer. Recently, specifically targeting the KRAS-G12C mutant, a frequently occurring KRAS mutation in human cancers, has shown promise in conquering KRAS-mutant cancers, and has inspired interest in this direction. We herein review the very recent progress achieved in the development of covalent inhibitors towards KRAS-G12C mutant, in combinational therapies and in proteolysis-targeting chimeras (PROTACs)-based approaches to disrupt KRAS-G12C protein. We provide insights for drug discovery against KRAS-G12C-mutated tumors and discuss the potential challenges in this field.

Hollow-structured nanoparticles as an anticancer drug carrier / 中国药理学与毒理学杂志

Many drug candidates identified from natural products are poorly water-soluble. The surfactants used to disperse the hydrophobic anticancer drugs in water may cause a serious of acute hypersensitivity reactions. Nanotech?nology provides an alternative strategy for delivery of anticancer drugs. Drugs can be encapsulated or attached to the nanomaterials such as lipids, polymers and solid-core nanoparticles. In the present study, porous inorganic nanoparti?cles have been utilized for delivery of water-insoluble anticancer drugs. The synthesized nanoparticles were functional?ized with different organic polymers. The porous nanoparticles were readily internalized by human glioblastoma U-87 MG cells, and didn't display cytotoxicity. The internalized nanoparticles were mainly localized in endosomes/lysosomes in cells. With the hydrophobic curcumin and carfilzomib as model drugs, intracellular delivery of hydrophobic anticancer drugs by the porous inorganic nanoparticles was studied. The porous nanoparticle-based encapsulation of hydrophobic drug provides the aqueous dispersion of the drugs. In endosomes/lysosomes mimicking buffers with a pH of 4.5-5.5, pH-dependent drug release was observed from drug loaded nanoparticles. The intracellular drug content and cytotoxicity were significantly higher for drug loaded nanoparticles than free drug. These results suggested porous inorganic nanoparticles might be a promising intracellular carrier for hydrophobic anticancer drugs.

A nanoemulsion-based delivery system for imatinib and in vitro anticancer efficacy

A self-nanoemulsifying drug delivery system (SNEDDS) composed of ethyl oleate, Tween 80 and polyethylene glycol 600 was prepared as a new route to improve the efficacy of imatinib. The drug-loaded SNEDDS formed nanodroplets of ethyl oleate stabilized by Tween 80 and polyethylene glycol 600 with a diameter of 81.0±9.5 nm. The nanoemulsion-based delivery system was stable for at least two months, with entrapment efficiency and loading capacity of 16.4±0.1 and 48.3±0.2%, respectively. Imatinib-loaded SNEDDS was evaluated for the drug release profiles, and its effectiveness against MCF-7 cell line was investigated. IC50 values for the imatinib-loaded SNEDDS and an imatinib aqueous solution were 3.1 and 6.5 µg mL-1, respectively.

Formulation and in vitro characterization of anticancer drugs encapsulated chitosan/multi-walled carbon nanotube nanocomposites

We aimed to combine the nanoscale structure with bio-molecules to open the door for novel biology and nanotechnologyapplications. Multi-walled carbon nanotube (MWCNT) was combined with the biocompatible polymer chitosan (Cs)producing the Cs/MWCNT nanocomposite and utilized as a drug carrier for three types of drugs, namely 5-fluorouracil,curcumin, and water-soluble curcumin derivative. The produced nanocomposite was with a homogenous well-definedstructure that proved by transmission electronic microscopy, FT-IR, X-ray diffraction, and thermal gravimetricanalysis. The results of cytotoxicity assay measurement showed that the curcumin encapsulated Cs or Cs/MWCNTnanocomposite presented higher toxicity towards MCF-7 cancer cells compared with RPE1 normal cells indicatingto the selective effectiveness of curcumin nanocomposite towards the destruction of the carcinogenic MCF-7 cells. Invitro release studies showed that Cs/MWCNT nanocomposite possesses better slow controlled release performancethan chitosan indicating that there is a strong association between the drug and CNTs which triggers the release of thedrug for controlled drug release purposes

Prescribing pattern of anticancer drugs in the medical oncology department of a tertiary care teaching hospital

Background: To study drug utilization of anticancer drugs in the oncology inpatient department (IPD) of Kamineni Hospitals, L.B. Nagar, Hyderabad, India.Methods: One hundred prescription records were screened and analysed as per the study parameters from the oncology IPD of Kamineni Hospitals, Hyderabad. Commonly used anticancer drugs were recorded; furthermore, different types of carcinomas were noted.Results: Age group of patients was in between 04 and 80 years, 62 were females and 38 were male patients. The most common type of carcinoma was carcinoma of the breast (28%). Cisplatin was the most commonly used anticancer drug (29%). Adjuvant drugs were used in 98% of the patients.Conclusions: Incidence of cancer is more in females than males. Adjuvant and cytoprotective drugs used may have had a bearing on the relatively lower incidence of adverse effects.

Analysis of the Anticancer Drug List between the National Essential Medicines List (2018) and the WHO Model List of Essential Medicines (2017) / 中国药学杂志

OBJECTIVE: To analyze the variation of the anticancer drug list in the National Essential Medicines List (NEML-2018) and compare with the WHO Essential Model List (WHO-EML-2017) considering the epidemic characteristics and current national conditions, in order to provide the reference and advice for the revision of NEML in the future. METHODS: The category, content, formulation, dosage forms, medicines for children and indication for use of anticancer drug list between the NEML-2018 and WHO-EML-2017 were compared, and the deficiency existing in the NEML-2018 was analyzed. RESULTS: Compared with the NEML-2012, the category and content of the anticancer drug list have been improved in the 2018th edition, which is more reasonable for clinical request. However, disadvantages still exist in the aspect of the content, formulation, dosage forms, medicines for children and indication for use compared with the WHO-EML-2017. CONCLUSION: Although the rationality of the category and content has been improved in the NEML-2018, it still needs to be further improved compared with the WHO-EML-2017, which provides guidance and indication for the revision of anticancer drug list of the NEML in the future.

Investigation and Analysis of Medication Information Labeling in 157 Package Inserts of Anticancer Drugs / 中国药房

OBJECTIVE： To investigate and analyze medication information labeling in package inserts of anticancer drugs， and to provide reference for clinical rational use. METHODS： The package inserts of anticancer drugs were collected from drug catalogues of 3 Third Grade Class A hospitals in Nanjin. Common problems of drug package inserts （whether the main contents arweree contradictory or not and whether the contents were fully expressed， etc.）， complete specific labeling items （detailed contents of “ADR” “contraindication” “precautions” and other items）， detailed intravenous injection dispensing guidance （solvent selection， precautions during dispensing， etc.）， package insert labeling difference of drugs with same general name and route of administration were evaluated according to Drug Package Inserts and Label Management Regulation，Regulations for Chemical Drugs and Biological Products for Treatment. RESULTS： A total of 157 package inserts for anticancer drugs were collected and divided into domestic drugs （80 pieces） and imported drugs （77 pieces） according to the source as well as also divided into oral preparation （44 pieces） and injection （113 pieces）. The common problems of package inserts for anticancer drugs contained contradictory main contents， incomplete description， Chinese character errors， missing items and simple description of drug interactions， etc. Compared with domestic or oral anticancer drugs， the labeling rate of each item in the import or injection anticancer drug package inserts was higher， but specific labeling items such as prevention and treatment of vomiting （＜20％） under “precautions” and interference of drugs on clinical tests （＜40％） were lower. The labeling rate of serious ADR after large dose or long-term use was all less than 41％ under the item of “drug overdose” （except for imported drugs）. The labeling rate of intravenous dispensing guidance of imported anticancer drug injection package inserts about preparations was higher than that of domestic ones. There were differences in labeling items as “precautions” （30/56，53.57％）， “pharmacological toxicology” （29/56，51.79％）， “contraindication” （26/56，46.43％） among 56 groups of drug package inserts with same general name and route of administration. CONCLUSIONS： The labeling items for drug package inserts of anticancer drugs need to be further standardized and improved. It is recommended that the relevant departments force pharmaceutical manufacturers to regularly supplement the deficiencies in the package inserts to improve the safety of drug use in clinic.

Preoperative short course radiotherapy with concurrent and consolidation chemotherapies followed by delayed surgery in locally advanced rectal cancer: preliminary results

PURPOSE: This study aimed to assess complications and outcomes of a new approach, that is, combining short course radiotherapy (SRT), concurrent and consolidative chemotherapies, and delayed surgery. MATERIALS AND METHODS: In this single arm phase II prospective clinical trial, patients with T3-4 or N+ M0 rectal adenocarcinoma were enrolled. Patients who received induction chemotherapy or previous pelvic radiotherapy were excluded. Study protocol consisted of three-dimensional conformal SRT (25 Gy in 5 fractions in 1 week) with concurrent and consolidation chemotherapies including capecitabine and oxaliplatin. Total mesorectal excision was done at least 8 weeks after the last fraction of radiotherapy. Primary outcome was complete pathologic response and secondary outcomes were treatment related complications. RESULTS: Thirty-three patients completed the planned preoperative chemoradiation and 26 of them underwent surgery (24 low anterior resection and 2 abdominoperineal resection). Acute proctitis grades 2 and 3 were seen in 11 (33.3%) and 7 (21.2%) patients, respectively. There were no grades 3 and 4 subacute hematologic and non-hematologic (genitourinary and peripheral neuropathy) toxicities and perioperative morbidities such as anastomose leakage. Grade 2 or higher late toxicities were observed among 29.6% of the patients. Complete pathologic response was achieved in 8 (30.8%) patients who underwent surgery. The 3-year overall survival and local control rates were 65% and 94%, respectively. CONCLUSION: This study showed that SRT combined with concurrent and consolidation chemotherapies followed by delayed surgery is not only feasible and tolerable without significant toxicity but also, associated with promising complete pathologic response rates.

Marine drugs for cancer: surfacing biotechnological innovations from the oceans

This review will discuss the contributions of marine natural molecules, a source only recently found to have pharmaceutical prospects, to the development of anticancer drugs. Of the seven clinically utilized compounds with a marine origin, four are used for the treatment of cancer. The development of these drugs has afforded valuable knowledge and crucial insights to meet the most common challenges in this endeavor, such as toxicity and supply. In this context, the development of these compounds will be discussed herein to illustrate, with successful examples provided by cytarabine, trabectedin, eribulin and brentuximab vedotin, the steps involved in this process as well as the scientific advances and technological innovation potential associated with developing a new drug from marine resources.

Research Progress in Transporter and Tumor Therapy and Prognosis / 中国药学杂志

With the increased incidence rate of cancer and the resistance of anticancer drugs, many further research concentrated on the transporter mediated tumor cell proliferation, the effectiveness of anticancer drugs and the malignant degree of tumor tissue. The study showed that transporter expression plays an important role in cancer therapy and prognosis. This review focuses on recent insights into the correlation among transporter, cancer therapy, resistance of anticancer drugs and the adverse effect of them.

Paclitaxel: A Landmark Natural Anticancer Drug / 世界科学技术-中医药现代化

As a most effective monomer composition from bark of Pacific Yew,paclitaxel and its derivatives are used in clinical practice as broad spectrum anticancer drugs.Since its discovery in the 1970 s,many researches had been carried out,mainly focusing on the modification,structure-activity relationship and pharmacological activity.The great successes pressed ahead the development of a series of taxol-like drugs,including taxol,docetaxel,cabazitaxel,larotaxel.Nowadays,studies of taxol are still the hotpots,which concentrated on the new source such as cultivation of tissue,fungus culture and new dosage forms.As the representative of drugs research from natural source,taxol is worth to be summarized of its history and ongoing development for looking forward to bring new innovation mentality in new drugs.

Historical story on natural medicinal chemistry: Rapamycin / 中草药

The study on natural product chemistry plays an important role in drug development and microbe is one of the main sources of new drugs. Rapamycin is isolated from the bacterium ensconced in a sample of Easter Island's soil, the compound has led to several approved immunosuppressant and anticancer drugs. The researchers studying on the target of rapamycin have got the "Nobel-class" achievements. In this paper, the discovery and study on rapamycin is summarized to provide the references for future related research.

Study the release kinetics of curcumin released from PVA/curcumin composites and its evaluation towards hepatocarcinoma.

The polymer composites based on Polyvinyl alcohol loaded with different concentrations of commercial curcumin were prepared to be applied forcontrolled release drug delivery system to overcome the growth promotion of tumor cells. The prepared composites were subjected to drug release in aqueous media at room temperature. It was found that the amount of the released curcumin changed according to different pH media and the concentration of the loaded drug onto the polymer carrier. The diffusion coefficient of the released curcumin from the prepared composites was found to be 2.739X10-2, 1.638X10-2, and 5.777X10-4 in basic, acidic and neutral solution respectively according to Higuch's equation. The results of the in/vitro cytotoxic activity of the released curcumin showed sustained antiproliferative potency up to 30 % growth inhibition against the human liver cancer cell line (HEPG2) which extended to 25 days, to overcome hepatocarcinoma.

Toxicological Study on the Anticancer Bioactive Fraction AMH-T of Lichen / 昆明医科大学学报

Objective To investigate the effects of anticancer bioactive fraction AMH-T of lichen on blood routine,organ coefficient and organ morphology by canying out short-term repeated dose toxicity test in rat so as to provide evidence for the development of anticancer drugs.Methods The nude mice were randomly divided into 5 groups:DDP group,DMSO group,and three AMH-T groups with the dosage of 50mg/kg,100mg/kg,and 200 mg/kg respectively.The weights of the mice were recorded every four days.At the end of the experiment,automatic biochemical analyzer and blood cell analyzer were applied to detect the serum biochemical indicators and blood routine indexes.The mice were dissected to observe the pathological changes in main organs.Heart,liver,spleen,kidney and testicle were weighed for organ coefficient calculation.Results In short-term repeated dose toxicity test,AMH-T significantly increased blood ALT and AST levels (P＜0.01) and significant change was found in other blood biochemical indexes and blood routine indexes.AMH-T had no obvious effect on weight,development of heart,liver,spleen,kidney and testicle.Conclusion When subcutaneous injection is performed,AMH-T shows hepatotoxicity,but it shows no toxicity on bone marrow hematopoietic function.

Examination Regarding the Simple Suspension Method using Oral Anticancer Drugs / 社会薬学

To administer oral anticancer drugs safely, the simple suspension method has been introduced in many hospitals. Therefore, concerning drugs for which it is unclear whether or not this method is applicable, testing must be able to be conducted at any time. In this study, we investigated 20 oral anticancer drugs to expand information on the application of the simple suspension method. Disintegration/suspension and permeability tests were conducted, as described in the 3rd version of the Tube Administration Handbook for Oral Drugs. All products were disintegrated/suspended after 10 minutes. On permeability tests, there was no residue in any tube for tubal feeding. On the final evaluation, the products were regarded as suitable (grade 1). Bicalutamide tablets (80 mg, TCK and KN), which were analyzed in this study, were regarded as suitable (grade 1) on the final evaluation. On the other hand, the simple suspension method is not applicable for a brand-name drug, Casodex^® tablets (80 mg). This may be related to the different additives. Furthermore, the results suggest that, even when the simple suspension method is not applicable for a brand-name drug, it may become applicable for generic drugs. This may provide a new merit for promoting the use of generic drugs.

A Case of Sudden Onset Septicemia in Recurred Gastric Cancer Following S1 Plus Docetaxel Treatment

Pyogenic liver abscess in patients with malignant disease is a fatal state and is easily diagnosed. We presented a rare case of sudden fatal septicemia following anticancer treatment for recurred gastric cancer due to multiple liver abscesses which could not be diagnosed. A 72-year-old male with recurred gastric cancer received anticancer agents. He had a history of distal gastrectomy with right hepatic lobectomy for hepatic metastasis. He received anticancer treatment in the outpatient's service center periodically, and his performance status was preserved with nothing in particular. After administrating docetaxel, he suddenly developed septicemia and multiple organ failure and died 5 days after strong medical supports. Pathological autopsy revealed that multiple minute abscesses of the liver which could not be detected macroscopically were the causes of fatal septicemia. The etiology, therapies and prognosis of rare entity are being discussed.

Collagen Gel Droplet-Embedded Culture Drug Sensitivity Test (CD-DST) for a Leiomyosarcoma Originating in the Inferior Vena Cava / 日本心臓血管外科学会雑誌

The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) identifies effective anticancer drug using resected tumor specimen, enabling tailor-made chemotherapy for a rare tumor. We report a case of the patient with leiomyosarcoma originating in the inferior vena cava, to which CD-DST was applied. This application has not been previously reported to the best of our knowledge. A 61-year-old woman consulted a nearby hospital because of abdominal pain. Computed tomography revealed an inferior vena cava tumor. The tumor was resected with the inferior vena cava, which was reconstructed with a 16 mm ePTFE graft. The tumor was diagnosed as leiomyosarcoma histopathologically. CDDP, VP-16, ADR, and VDS were CD-DST showed the tumor to be sensitive. Her postoperative course has been good without recurrence of tumor for 6 months, and the results of CD-DST may be helpful for chemotherapy strategy in case of recurrence.

Caracterização físico-química do potencial agente antineoplásico Beta-lapachona / Physicochemical characterization of the anticancer drug Beta-lapachone

A Beta-lapachona tem inspirado uma série de trabalhos científicos, tendo em vista os inúmeros estudos farmacológicos relatados na literatura, que comprovam suas atividades antibacteriana, antifúngica, antitripanossômica, antiviral, anti-inflamatória e antineoplásica. Devido a sua potente atividade anticancerígena, este fármaco encontra-se, atualmente, em estudo clínico de fase II para o tratamento de câncer pancreático. O objetivo deste estudo foi determinar as propriedades físico-químicas deste ativo com o emprego de diversas ferramentas analíticas, como, difração de Raios X, infravermelho, análises térmicas, microscopia eletrônica de varredura e ensaio de dissolução. Os resultados obtidos na difração de raios X revelaram o padrão policristalino do fármaco; o infravermelho identificou os principais grupos funcionais da Beta-lapachona; os dados das análises térmicas apresentaram características de um produto cristalino e de alta pureza; a eletromicrografia demonstrou sua forma cristalina, como cristais acidulares bem definidos de tamanho regular, corroborando com os dados do difratograma. No estudo de dissolução comprovamos que a Beta-lapachona é praticamente insolúvel em água, sendo necessário o desenvolvimento de estratégias tecnológicas destinadas a melhorar a sua solubilidade em meio aquoso. Dessa forma, a determinação das principais características físico-químicas da Beta-lapachona será extremamente útil na identificação de problemas que possam vir a surgir durante a formulação e auxiliará no desenvolvimento de formas farmacêuticas mais eficazes e com qualidade.

A series of scientific papers on Beta-lapachone has been inspired by the numerous pharmacological reports in the literature that demonstrate its antibacterial, antifungal, antitrypanosomal, antiviral, anticancer and anti-inflammatory activities. Owing to its potent anticancer activity, this drug is currently undergoing phase II clinical trials for the treatment of pancreatic cancer. The aim of this study was to determine the physicochemical properties of this drug by means of several analytical tools, such as X-ray diffraction (XRD), infrared (IR) spectroscopy, thermal analysis, scanning electron microscopy (SEM) and dissolution test. The XRD patterns showed the polycrystalline state of the drug; IR spectroscopy identified the main functional groups of Beta-lapachone; the data from thermal analysis showed characteristics of a crystalline product of high purity and the SEM micrographs showed the crystalline form as well-defined acidulated crystals of regular size, corroborating the XRD patterns. In the dissolution test we found that Beta-lapachone is practically insoluble in water, necessitating the development of technological strategies to improve its solubility in aqueous media. Thus, the determination of the main physicochemical characteristics of Beta-lapachone will be extremely useful in identifying problems that may arise during the design and in the development of more effective and higher quality pharmaceutical forms of this drug.