A review of acute childhood leukemia in the University Hospital, Kuala Lumpur reveals no significant differences in either the epidemiological or clinical features between Malaysian and Caucasian children. BCG does not appear to have conferred any protection against the occurrence of leukemia. With the introduction of total therapy 4 of 10 patients with good prognostic features and 3 of 15 patients with poor prognostic features have survived 3 years. Prognosis appears to correlate with adopted clinical criteria.
Four complex flavanones, kurziflavolactones A [2], B [3], C [4], and D [5] and a complex chalcone 6 with an unprecedented carbon side chain on the flavanone or chalcone A ring have been isolated from a Malaysian plant, Cryptocarya kurzii (Lauraceae). Their structures were determined by extensive spectroscopic analysis, especially 2D nmr experiments. Compounds 3 and 6 showed slight cytotoxicity against KB cells, with IC50 values of 4 and 15 micrograms/ml, respectively. A biosynthetic pathway for the formation of these compounds is suggested.
Bioassay-guided fractionation of the extracts of Zieridium pseudobtusifolium and Acronychia porteri led to the isolation of 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone [1], which showed activity against (KB) human nasopharyngeal carcinoma cells (IC50 0.04 micrograms/ml) and inhibited tubulin assembly into microtubules (IC50 12 microM). Two other known flavonols, digicitrin [2] and 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone [5], were also isolated together with three new ones, 3-O-demethyldigicitrin [3], 3,5,3'-trihydroxy-6,7,8,4'-tetramethoxyflavone [4], and 3,5-dihydroxy-6,7,8,3',4'-pentamethoxyflavone [6]. All of these flavonols showed cytotoxic activity against KB cells.
Intensive chemotherapy has prolonged survival in cancer patients. Unfortunately it has also predisposed them to unusual infections because of their immunocompromised state. We report a case of fungal septicaemia caused by Geotrichum candidum, an imperfect yeast of low virulence in a young girl with acute lymphoblastic leukaemia. It was successfully treated with amphotericin B. The morphological characteristics of this fungus leading to its identification are described.
Matched MeSH terms: Antineoplastic Agents/adverse effects; Antineoplastic Agents/therapeutic use
Bioassay-guided fractionation of an ethyl acetate extract of Fissistigma lanuginosum led to the isolation of the known chalcone pedicin [1], which inhibited tubulin assembly into microtubules (IC50 value of 300 microM). From the same EtOAc fraction, two new condensed chalcones, fissistin [2] and isofissistin [3], which showed cytotoxicity against KB cells, were also obtained, together with the inactive dihydropedicin [4] and 6,7-dimethoxy-5,8-dihydroxyflavone [5]. In addition, the aminoquinones 6, 8, and 9 were isolated from the alkaloid extract. These compounds were artifacts, prepared by treatment of 1, 4, and 2, respectively, with NH4OH. The structures of the new compounds were elucidated by spectral methods, especially 2D nmr.
A 30-year old female who initially had typical endometriosis treated according to a standard regimen later developed numerous highly vascular endometrial polyps on the vagina, cervix, ureter, serosal surfaces of the uterus, pouch of Douglas (POD) and other areas of pelvic peritoneum as well as the endometrium 8 months after withdrawal of treatment with Zoladex gonadotrophin releasing hormone (GnRH) agonist used for treatment of this disease. We postulate that these polyps developed as a rebound phenomenon upon withdrawal of Zoladex. We believe this is the first report of this complication following use of GnRH analogue.
Overall survival of nasopharyngeal carcinoma (NPC) at UICC stage IV still remains unsatisfactory even with combination chemotherapy (CT) and radio-therapy (RT). In view of the association of reactivation of Epstein-Barr virus (EBV) with the development and recurrence of NPC, immunotherapy in the form of transfer factor (TF) with specific activity against EBV (TF-B1) was suggested as an adjuvant to a combination of CT and RT in order to improve survival. In the present study, 6 UICC stage IV patients received TF-B1 and another 6 patients matched for disease stage were given TF prepared from peripheral blood leucocytes (TF-PBL). Results were compared with another 18 patients matched by age, sex, and stage of disease who received standard therapy without TF during the same period (C group). After a median follow up of 47.5 months, the survival for the TF-B1 group was found to be significantly better (P = < 0.05) than the PBL and C group. While the 8 patients with distant metastasis (DM), not treated with TF-B1 (6 in the control and 2 in the PBL group), died due to progressive disease (average survival being 14.3 months), both patients with DM in the TF-B1 group had complete remission: one died of tuberculosis after surviving for 3.5 years and another is still alive, disease free, after 4.2 years. Although the series involved a small number of cases, the apparent effect of adjuvant immunotherapy in the form of TF with anti-EBV activity is of considerable interest.
The cytotoxicity of goniothalamin was found to be strong towards both cancerous (HGC-27, MCF-7, PANC-1, HeLa), and non-cancerous (3T3) cell lines, especially in cases of dividing cells. Drug exposure studies indicated that the cytotoxic action of goniothalamin was time- and dose-dependent. At the ultrastructural level, goniothalamin-induced cytotoxicity revealed a necrotic mode of cell death towards MCF-7 cells.
Five patients treated with hydroxyurea for various haematological malignancies developed multiple painful oral ulcers. Their neutrophil counts were either normal or elevated. The ulcers disappeared with cessation of hydroxyurea. Oral ulcers recurred when hydroxyurea was resumed in one of the patients. As the patients were unable to tolerate this painful side effect, hydroxyurea had to be discontinued. Appearance of painful oral ulceration seems to be independent of dosing rate or total cumulative dose of hydroxyurea.
Matched MeSH terms: Antineoplastic Agents/adverse effects*; Antineoplastic Agents/therapeutic use
A case of germinoma originating in the basal ganglia and thalamus is presented. This tumour most commonly originates during childhood and adolescence, at pineal and suprasellar regions. In the early stages, the diagnosis of germinoma in the basal ganglion and thalamus is difficult because of its rarity and non-specific findings. The computed tomography (CT) and magnetic resonance imaging (MRI) findings though non-diagnostic, are discussed here. A few differential diagnoses had been discussed with radiological abnormality. Open biopsy done in this case proved to be two-cell pattern germinoma. Early detection of the tumour is desirable, since this tumour is highly sensitive to radio and chemotherapy and is potentially curable. Our patient was treated with combined chemotherapy and the response was well and no residual tumour or recurrence was seen on the repeated imaging modality, however his neurological deficits remained unchanged.
Matched MeSH terms: Antineoplastic Agents/therapeutic use
A pilot study of Formestane or 4-Hydroxyandrostenedione (Lentaron), a new endocrine agent, was conducted on 18 postmenopausal patients with locally advanced and metastatic breast cancer. 16 patients were evaluable for response and objective responses were seen in 4 patients (25%). Stabilisation of disease was seen in 5 patients (32%). Out of 17 patients evaluable for toxicity, 3 (18%) reported adverse effects including hot flushes, lethargy and myalgia. Adverse effects were mild, transient and no patient required discontinuation of drug. Our study confirms that Formestane is a well tolerated endocrine agent with low toxicity and reasonable efficacy in postmenopausal patients with locally advanced and metastatic breast cancer.
Four new bisindoles of the vobasine-iboga type, conodiparines A-D were obtained from Tabernaemontana corymbosa which showed appreciable activity in reversing resistance in vincristine-resistant KB cells.
A series of indole alkaloids of the aspidofractinine-type was assessed for their potential in reversing MDR in vincristine-resistant KB cells. Of the compounds tested, kopsiflorine, kopsamine, pleiocarpine, 11-methoxykopsilongine, lahadinine A and N-methoxycarbonyl-11,12-methylenedioxy-delta 16,17-kopsinine were found to show appreciable activity.
The EtOH extract of the leaves of Holarrhena curtisii yielded five new steroidal alkaloids: 17-epi-holacurtine (3), 17-epi-N-demethylholacurtine (4), holacurtinol (5), 3alpha-amino-14beta-hydroxypregnan-20-one (7), and 15alpha-hydroxyholamine (8), in addition to the known compounds, holacurtine (1), N-demethylholacurtine (2), and holamine (6). All eight compounds showed significant cytotoxic and leishmanicidal activities.