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Gemcitabine and vinorelbine treatment in cutaneous T-cell lymphoma in four patients

Affandi AM, Blumetti TP, Wells J, Hertzberg M, Fernandez-Peñas P

Australas J Dermatol, 2015 Nov;56(4):294-7.
PMID: 25496219 DOI: 10.1111/ajd.12270

Treatment options for advanced stage cutaneous T-cell lymphoma (CTCL) are limited by the their efficacy and side-effects profile. Gemcitabine, a pyrimidine analogue, has been reported to be efficacious in CTCL. Most of the studies published used gemcitabine as a single agent in treating advanced CTCL. Our small case series demonstrated that a combination of gemcitabine and vinorelbine induced partial remission in all four patients with refractory or advanced CTCL, although the effects were not sustained for a long duration (2-6 months). Two patients had neutropenia and one had acute hepatitis, requiring discontinuation of treatment.

Matched MeSH terms: Vinblastine
Fulltext First report on a novel Nigrospora sphaerica isolated from Catharanthus roseus plant with anticarcinogenic properties

Ayob FW, Simarani K, Zainal Abidin N, Mohamad J

Microb Biotechnol, 2017 Jul;10(4):926-932.
PMID: 28612376 DOI: 10.1111/1751-7915.12603

This paper reports on the vinca alkaloid produced by a novel Nigrospora sphaerica isolated from Catharanthus roseus. Through liquid chromatography-mass spectrometry (LCMS), only the crude mycelia extract of this fungus was positive for determination of vinblastine. This vinca alkaloid was then purified by using high-performance liquid chromatography (HPLC) and tested for cytotoxicity activity using MTT assays. The breast cell line cancer (MDA-MB 231) was treated with a purified vinblastine which was intracellulary produced by N. sphaerica. The purified vinblastine from extracted leaf of C. roseus was used as a standard comparison. A positive result with a value of half maximal inhibitory concentration (IC50 ) of > 32 μg ml-1 was observed compared with standard (IC50 ) of 350 μg ml-1 only. It showed that a vinblastine produced by N. sphaerica has a high cytotoxicity activity even though the concentration of vinblastine produced by this endophytic fungus was only 0.868 μg ml-1 .

Matched MeSH terms: Vinblastine/isolation & purification; Vinblastine/metabolism*; Vinblastine/chemistry
Fulltext Characterisation of Silver Nanoparticles using a Standardised Catharanthus Roseus Aqueous extract

Siti Zulaikha Ghozali, Mohd Nazri Ismail, Nor Hazwani Ahmad

Malaysian Journal of Medicine and Health Sciences, 2018;14(102):1-6.
MyJurnal

The biosynthesis of nanoparticles has been proposed as a cost-effective and environmental friendly alternative to chemical and physical methods. The present study was aimed to characterise Catharanthus roseus (C. roseus)-silver nanoparticles (AgNPs) using a standardised C. roseus aqueous extract. Methods: The standardisation was performed by using Liquid Chromatography/Time-of-Flight ion trap Mass Spectrometry. An optimised C. roseus-AgNPs have been previously synthesised. Further characterisation of C. roseus-AgNPs was evaluated by zeta potential analysis and fourier transform infrared spectroscopy (FTIR). Results: The chromatography analysis has revealed presence of thirteen possible indole alkaloids in C. roseus extract which were lochrovicine, lochnerine, vinleurosine, vindolinine, tabersonine, catharanthine, serpentine, catharosine, vincristine, catharine, ajmalicine, vinleurosine, and vindolicine. Zeta potential analysis exhibited the value at -16.6 mV. FTIR spectrum of C. roseus aqueous extract showed the absorption band at 3210.83 cm-1 (C-H stretch), 2934.11 (C-H bond), 1578.15 (N=O stretch), 1388.76 and 1314.89 (N=O bend), 1119.29 (C-O bond) and 729.94 (C-Cl bond). In comparison, FTIR spectrum of C. roseus-AgNP s showed the absorption band at 2925.01 and 2924.97 (C-H bond), 1622.93 (C-C=C symmetric stretch), 1383.19 and 1384.13 (N-O bend), 1037.92/1038.76/1238.3/1117.2 (C-O bond), 3169.4 (O-H bond), 774.59 and 691.53 (C-Cl bond). Conclusion: The present findings have shown that the C. roseus aqueous extract contains alkaloids that may responsible as reducing and stabilising agents in the synthesis of AgNPs.

Matched MeSH terms: Vinblastine
Catharanthus roseus Aqueous Extract is Cytotoxic to Jurkat Leukaemic T-cells but Induces the Proliferation of Normal Peripheral Blood Mononuclear Cells

Ahmad NH, Rahim RA, Mat I

Trop Life Sci Res, 2010 Dec;21(2):101-13.
PMID: 24575203

Research on natural products has been widely used as a strategy to discover new drugs with potential for applications in complementary medicines because they have fewer side effects than conventional drugs. The aim of the present study was to evaluate the in vitro cytotoxic effects of crude aqueous Catharanthus roseus extract on Jurkat cells and normal peripheral blood mononuclear cells (PBMCs). The aqueous extract was standardised to vinblastine by high performance liquid chromatography (HPLC) and was used to determine cytotoxicity by the MTS [3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. DNA fragmentation assay was employed to determine if cell death was due to apoptosis. The results showed that the aqueous extract induced cell death of Jurkat cells at 24, 48 and 72 hours post-treatment in a time- and dose-dependent manner. However, cells treated at 48 and 72 hours produced higher cytotoxic effects with half maximal inhibitory concentration (IC50) values of 2.55 μg/ml and 2.38 μg/ml, respectively. In contrast, the extract induced normal PBMC proliferation, especially after 24 hours treatment with 1000 μg/ml. This result indicates that the C. roseus crude aqueous extract showed differential effects of inhibiting the proliferation of the Jurkat cell line and promoting the growth of PBMCs. These data suggest that the extract may be applicable for modulating the normal and transformed immune cells in leukaemia patients.

Matched MeSH terms: Vinblastine
A simple and rapid HPLC-DAD method for simultaneously monitoring the accumulation of alkaloids and precursors in different parts and different developmental stages of Catharanthus roseus plants

Pan Q, Saiman MZ, Mustafa NR, Verpoorte R, Tang K

J Chromatogr B Analyt Technol Biomed Life Sci, 2016 Mar 1;1014:10-6.
PMID: 26854826 DOI: 10.1016/j.jchromb.2016.01.034

A rapid and simple reversed phase liquid chromatographic system has been developed for simultaneous analysis of terpenoid indole alkaloids (TIAs) and their precursors. This method allowed separation of 11 compounds consisting of eight TIAs (ajmalicine, serpentine, catharanthine, vindoline, vindolinine, vincristine, vinblastine, and anhydrovinblastine) and three related precursors i.e., tryptophan, tryptamine and loganin. The system has been applied for screening the TIAs and precursors in Catharanthus roseus plant extracts. In this study, different organs i.e., flowers, leaves, stems, and roots of C. roseus were investigated. The results indicate that TIAs and precursor accumulation varies qualitatively and quantitatively in different organs of C. roseus. The precursors showed much lower levels than TIAs in all organs. Leaves and flowers accumulate higher level of vindoline, catharanthine and anhydrovinblastine while roots have higher level of ajmalicine, vindolinine and serpentine. Moreover, the alkaloid profiles of leaves harvested at different ages and different growth stages were studied. The results show that the levels of monoindole alkaloids decreased while bisindole alkaloids increased with leaf aging and upon plant growth. The HPLC method has been successfully applied to detect TIAs and precursors in different types of C. roseus samples to facilitate further study of the TIA pathway and its regulation in C. roseus plants.

Matched MeSH terms: Vinblastine
Adjuvant cytotoxic chemotherapy following Wertheim radical hysterectomy for cervical cancer

Sivanesaratnam V, Sen DK, Jayalakshmi P

Aust N Z J Obstet Gynaecol, 1987 Aug;27(3):231-3.
PMID: 2449159

Patients at high risk of recurrence or metastases following radical surgery for Stage 1B and 2A cervical carcinoma include those with pelvic node metastases, lymphatic or vascular space permeation in the cervix by tumour cells, large size of the primary tumour, involvement of the full thickness of the cervix and parametrial spread. We report the initial results of adjuvant chemotherapy using a combination of cisplatinum, bleomycin and vinblastine in 22 patients who had undergone Wertheim radical hysterectomy and were thought to be at high risk of developing recurrence. The mean duration of follow-up was 23 months. All are alive after follow-up ranging from 13 to 43 months. Three patients developed recurrences--one in the pelvis, another at the posterior aspect of the urethral meatus and the third developed pulmonary secondaries at 20 to 23 months after surgery. Toxicity from the chemotherapy was acceptable.

Matched MeSH terms: Vinblastine/administration & dosage
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: Vinblastine/therapeutic use
Bisleuconothine A Induces Autophagosome Formation by Interfering with AKT-mTOR Signaling Pathway

Wong CP, Seki A, Horiguchi K, Shoji T, Arai T, Nugroho AE, et al.

J Nat Prod, 2015 Jul 24;78(7):1656-62.
PMID: 26176165 DOI: 10.1021/acs.jnatprod.5b00258

We have previously reported that bisleuconothine A (Bis-A), a novel bisindole alkaloid isolated from Leuconotis griffithii, showed cytostatic activity in several cell lines. In this report, the mechanism of Bis-A-induced cytostatic activity was investigated in detail using A549 cells. Bis-A did not cause apoptosis, as indicated by analysis of annexin V and propidium iodide staining. Expression of all tested apoptosis-related proteins was also unaffected by Bis-A treatment. Bis-A was found to increase LC3 lipidation in MCF7 cells as well as A549 cells, suggesting that Bis-A cytostatic activity may be due to induction of autophagy. Subsequent investigation via Western blotting and immunofluorescence staining indicated that Bis-A induced formation but prevented degradation of autophagosomes. Mechanistic studies showed that Bis-A down-regulated phosphorylation of protein kinase B (AKT) and its downstream kinase, PRAS40, which is an mTOR repressor. Moreover, phosphorylation of p70S6K, an mTOR-dependent kinase, was also down-regulated. Down-regulation of these kinases suggests that the increase in LC3 lipidation may be due to mTOR deactivation. Thus, the cytostatic activity shown by Bis-A may be attributed to its induction of autophagosome formation. The Bis-A-induced autophagosome formation was suggested to be caused by its interference with the AKT-mTOR signaling pathway.

Matched MeSH terms: Vinblastine/pharmacology
Fulltext Abdominal Lymphocyte-Depleted Hodgkin Lymphoma: A Rare Presentation

Kasinathan G, Kori AN, Hassan N

Int J Gen Med, 2019;12:405-409.
PMID: 31807052 DOI: 10.2147/IJGM.S232254

Background: Hodgkin lymphoma (HL) is a type of lymphoma that arises from the B lymphocytes. The four main subtypes of HL are the nodular sclerosing, mixed cellularity, lymphocyte rich and the lymphocyte depleted. Nodular sclerosis subtype accounts for majority of all classical HL, whereas lymphocytic depletion type accounts for less than 1%. The main objective of reporting this case is to share with the medical fraternity a rare presentation of abdominal lymphocyte-depleted classical Hodgkin lymphoma.
A 47-year-old gentleman of Malay ethnicity with no known pre-morbidities, presented to the haematology unit with a 2-month history of night fever, loss of weight, malaise, anorexia and abdominal swelling. Abdominal examination revealed a periumbilical and lower epigastric swelling measuring 6x6 cms. The swelling was non-tender, firm in consistency and smooth on palpation. The Contrast Enhanced Computed Tomography (CECT) imaging revealed an enlarged mesenteric mass measuring 5.8x6.9x5.7 cm and multiple enlarged aorta-caval lymph nodes. The mesenteric tumour histology and immunohistochemistry were consistent with lymphocyte depleted HL. He completed six cycles of intravenous ABVD polychemotherapy consisting of doxorubicin (Adriamycin) 25mg/m2, Bleomycin 10mg/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2. The Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET /CT) imaging post 2 cycles and 6 cycles of ABVD polychemotherapy showed complete metabolic response to chemotherapy.
Conclusion: Lymphocyte-depleted classical Hodgkin lymphoma (LDcHL) is a rare entity and is mostly diagnosed at a later stage rendering it a disease with poor prognostic outcomes. Early detection and prompt institution of therapy is crucial in the management of this disease.

Matched MeSH terms: Vinblastine
Fulltext Catharanthus roseus aqueous extract is cytotoxic to Jurkat Leukaemic T-cells but Induces the proliferation of normal peripheral blood mononuclear cells

Nor Hazwani Ahmad, Rohanizah Abdul Rahim, Ishak Mat

Trop Life Sci Res, 2010;21(2):-.
MyJurnal

Research on natural products has been widely used as a strategy to discover new drugs with potential for applications in complementary medicines because they have fewer side effects than conventional drugs. The aim of the present study was to evaluate the in vitro cytotoxic effects of crude aqueous Catharanthus roseus extract on Jurkat cells and normal peripheral blood mononuclear cells (PBMCs). The aqueous extract was
standardised to vinblastine by high performance liquid chromatography (HPLC) and was used to determine cytotoxicity by the MTS [3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. DNA fragmentation assay was employed to determine if cell death was due to apoptosis. The results showed that the aqueous extract induced cell death of Jurkat cells at 24, 48 and 72 hours posttreatment in a time- and dose-dependent manner. However, cells treated at 48 and 72 hours produced higher cytotoxic effects with half maximal inhibitory concentration (IC50)values of 2.55 µg/ml and 2.38 µg/ml, respectively. In contrast, the extract induced normal PBMC proliferation, especially after 24 hours treatment with 1000 µg/ml. This result indicates that the C. roseus crude aqueous extract showed differential effects of inhibiting the proliferation of the Jurkat cell line and promoting the growth of PBMCs. These data suggest that the extract may be applicable for modulating the normal and transformed immune cells in leukaemia patients.

Matched MeSH terms: Vinblastine