The mouth and oropharynx are among the ten most common sites affected by cancer worldwide, but global incidence varies widely. Five-year survival rates exceed 50% in only the best treatment centers. Causes are predominantly lifestyle-related: Tobacco, areca nut, alcohol, poor diet, viral infections, and pollution are all important etiological factors. Oral cancer is a disease of the poor and dispossessed, and reducing social inequalities requires national policies co-ordinated with wider health and social initiatives - the common risk factor approach: control of the environment; safe water; adequate food; public and professional education about early signs and symptoms; early diagnosis and intervention; evidence-based treatments appropriate to available resources; and thoughtful rehabilitation and palliative care. Reductions in inequalities, both within and between countries, are more likely to accrue from the application of existing knowledge in a whole-of-society approach. Basic research aimed at determining individual predisposition and acquired genetic determinants of carcinogenesis and tumor progression, thus allowing for targeted therapies, should be pursued opportunistically.
Khat chewing is a widespread habit that has a deep-rooted sociocultural tradition in Africa and the Middle East. The biological effects of khat are inadequately investigated and controversial. For the first time, we show that an organic extract of khat induces a selective type of cell death having all morphological and biochemical features of apoptotic cell death. Khat extract was shown to contain the major alkaloid compounds cathinone and cathine. The compounds alone and in combination also induced apoptosis. Khat-induced apoptosis occurred synchronously in various human cell lines (HL-60, NB4, Jurkat) within 8 h of exposure. It was partially reversed after removal of khat and the effect was dependent on de novo protein synthesis, as demonstrated by cotreatment with cycloheximide. The cell death was blocked by the pan-caspase inhibitor Z-VAD-fmk, and also by submicromolar concentrations of Z-YVAD-fmk and Z-IETD-fmk, inhibitors of caspase-1 and -8, respectively. The 50% inhibition constant (IC 50 ) for khat (200 mg ml À1 )-induced apoptosis by Z-VAD-fmk, Z-YVAD-fmk and Z-IETD-fmk was 8 Â 10 À7 M as compared to 2 Â 10 À8 M and 8 Â 10 À8 M, respectively. Western blot analysis showed a specific cleavage of procaspase-3 in apoptotic cells, which was inhibited by Z-VAD-fmk. The cell death by khat was more sensitively induced in leukaemia cell lines than in human peripheral blood leukocytes. It is concluded that khat induces a rather swift and sensitive cell death by apoptosis through mechanisms involving activation of caspase-1, -3 and -8.
BackgroundAn organic extract of the recreational herb khat (Catha edulis Forsk.) triggers cell death in various leukemia cell lines in vitro. The chemotherapeutics camptothecin, a plant alkaloid topoisomerase I inhibitor, was tested side-by-side with khat in a panel of acute myeloid leukemia cell lines to elucidate mechanisms of toxicity.ResultsKhat had a profound effect on MOLM-13 cells inducing mitochondrial damage, chromatin margination and morphological features of autophagy. The effects of khat on mitochondrial ultrastructure in MOLM-13 correlated with strongly impaired routine respiration, an effect neither found in the khat-resistant MV-4-11 cells nor in camptothecin treated cells. Enforced expression of anti-apoptotic Bcl-2 protein provided protection against camptothecin-induced cell death and partly against khat toxicity. Khat-induced cell death in MOLM-13 cells included reduced levels of anti-apoptotic Mcl-1 protein, while both khat and camptothecin induced c-FLIPL cleavage and procaspase-8 activation.ConclusionKhat activated a distinct cell death pathway in sensitive leukemic cells as compared to camptothecin, involving mitochondrial damage and morphological features of autophagy. This suggests that khat should be further explored in the search for novel experimental therapeutics.
This study describes the clinical and pathologic features of ameloblastomas seen in the 2 main craniofacial treatment centers in Kenya in the 10-year period between January 1995 and December 2005. A total of 184 patient records were analyzed for this study. Eighty-two (44.6%) of the patients were male, and 102 (55.4%) were female with an overall age range of 10 to 80 years (mean, 30.2 years; SD, 14.1 years). There was no significant difference in gender presentation of ameloblastomas, although females presented at a slightly older age. The mean age for males was 29.9 years, and for females, it was 30.5 years. Patients generally tended to seek medical advice late, with the mean duration at first presentation of 46.3 months for males and 44.4 months for females. Most of the ameloblastomas (n = 172; 93.5%) were located in the mandible, 11 (6.0%) were in the maxilla, and 1 (0.5%) was in the soft tissues. Presenting symptoms included swelling (n = 182; 98.9%), pain (n = 64; 36.0%), mobile teeth/history of extraction (n = 104; 57.5%), purulent discharge (n = 39; 21.7%) and paresthesia (n = 10; 5.6%). The posterior mandible was the most commonly affected site, whereas maxillary ameloblastomas tended to occur in anterior sites. One hundred fifty-three ameloblastomas (83.2%) were of the solid/multicystic subtype; 8 (5.3%) were unicystic; 1 (0.5%) was of extraosseous origin; 1 (0.5%) was desmoplastic; 9 (6.0%) were malignant, and 12 of the records had no histopathologic pattern specified.
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