Mechanism of cancer chemopreventive activity of green Tea.
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Animals↗
Biomedical subjects
N Ahmad
Publications and source records attributed to N Ahmad.
Dietary intake of pesticides: State of Kuwait total diet study.
The State of Kuwait conducted a total diet study (TDS) to determine the dietary intakes of selected pesticides. This paper reports the results of this study. A national food consumption survey was performed and core food lists for different population groups were established representing the total diet of the Kuwaiti population. Food items (table-ready) were purchased/prepared and analysed for their contents of organophosphate/organochlorine carbamate, benzimidazole and phenylurea pesticides according to the US FDA Pesticide Analytical Manual (PAM I). Dietary intakes of these pesticides are presented for 19 population groups, which range from infants to elderly adults. The intakes of selected population groups are compared with representative findings from the US FDA/TDS and data published from other countries. In general, the average daily intakes were well below acceptable limits, but higher than those reported from developed countries.
Adolescent↗
Determination of organochlorine and organophosphate pesticide residues in fruits, vegetables and sediments.
A method is described for the determination of organochlorine and organophosphate pesticide residues in fruits, vegetables and sediments. The concentrated solvent extract was sealed in a polymeric membrane tube, dialysed in cyclohexane and the solvent replaced with hexane. The organophosphates were analysed on a specific thermionic detector without further clean-up. For the organochlorine pesticides the extract was eluted through 3 g of alumina and analysed on GC/ECD. The clean-up for sediment extract was carried out on a 10 g alumina column with 100 mL hexane containing 5% acetone and the eluate was concentrated to 5 mL. The detection limit for organophosphates on a 40 g sample and a final volume of 10 mL was on the average 0.01 mg/kg. The detection limit for organochlorine pesticides, with the final volume of 25 mL, was 0.005 mg/kg for all pesticides except for p,p'-DDT and endosulfan sulphate, which was 0.01 mg/kg. The detection limit for organochlorine pesticides in sediment, with the final volume of 2 mL, was less than 1 microgram/kg and for organophosphate pesticides less than 10 micrograms/kg when the final volume was made to 0.5 mL. At the detection limits the method produced a very high coefficient of variation for both organochlorine and organophosphate pesticides.
Chromatography, Gas↗
Green tea in chemoprevention of cancer.
The concept of prevention of cancer using naturally occurring substances that could be included in the diet consumed by the human population is gaining increasing attention. Tea, next to water, is the most popularly consumed beverage in the world and it is grown in about 30 countries. Abundant data, amassed from several laboratories around the world in the last ten years, provided convincing evidence that polyphenolic antioxidants present in tea afford protection against cancer risk in many animal-tumor bioassay systems. The epidemiological studies, though inconclusive, have also suggested that the consumption of tea is associated with a lowered risk of cancer. Much of this work has been done on green tea; less is known about black tea. Green tea contains many polyphenolic antioxidants, and (-)-epigallocatechin-3-gallate (EGCG) is the key polyphenolic antioxidant believed to be responsible for most of the cancer chemopreventive properties of green tea. This review will discuss these effects and the molecular mechanisms associated with the biological response to green-tea polyphenols.
Humans↗
Green tea polyphenols and cancer: biologic mechanisms and practical implications.
Polyphenolic compounds in fruits and vegetables have been associated with lower risk of some diseases, including cancer. Recent research has shown that the polyphenolic antioxidants in green tea possess cancer chemopreventive effects. This review discusses the cancer chemopreventive effects associated with green tea and the molecular mechanisms that underlie the broad anticarcinogenic effect of polyphenols in green tea.
Anticarcinogenic Agents↗
Upregulation of E2F transcription factors in chemically induced mouse skin tumors.
E2F family of transcription factors plays an important role in cell cycle regulation, oncogenesis and differentiation. E2Fs are a family of heterodimeric transcription factors composed of E2F-like and DP-like subunits. They regulate expression of specific genes controlling cellular proliferation by binding to specific sequences within the promoter regions of these target genes and affecting their transcription in a cell cycle dependent manner. Recent studies have suggested an essential role of Rb/E2F pathway in the passage of cells through the G1 phase of the cell cycle. To better understand the role of these transcription factors in epithelial tumorigenesis, we compared the expression of various proteins involved in the Rb/E2F pathway in epidermis and 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA) promoted papillomas on SENCAR mouse skin. Western blot analysis data showed 3.0- to 7.6-fold upregulation of E2F-1, E2F-2, E2F-3, E2F-4 and E2F-5 in tumors compared to normal epidermis. In tumors, the protein expression of DP-1 did not show significant change whereas that of DP-2 showed a 2.2-fold increase. Compared to normal epidermis, a significant upregulation of pRb (6.3-fold) and p107 (13-fold) was also observed in tumors. The protein expression of p130 was not detectable either in normal epidermis or in tumors. These data suggest that the overexpression of E2F proteins may be involved in the G1-S phase dysregulation that occurs during mouse skin tumorigenesis.
9,10-Dimethyl-1,2-benzanthracene↗
Prostate cancer chemoprevention by green tea.
Prostate cancer (PCA) is one of the most invasive cancers and the second leading cause of cancer-related deaths among males in the United States. According to an estimate, 1 of every 11 American men will eventually develop PCA. One way to reduce the occurrence of cancer is through chemoprevention. PCA represents an excellent candidate disease for chemoprevention because it is typically diagnosed in men over 50 years of age, and therefore even a modest delay in neoplastic development achieved through pharmacological or nutritional intervention could result in a substantial reduction in the incidence of clinically detectable disease. The ideal agent(s) suitable for chemoprevention of PCA should be the one(s) that has proven efficacy in the laboratory experiments on one hand, and also possesses proven epidemiological basis on the other hand. This review attempts to address the issue of possible uses of tea, especially green tea, for the prevention of PCA. We are providing the experimental as well as the epidemiological basis for this possibility. Many laboratory experiments conducted in cell culture systems and in animal models have shown the usefulness of green tea, and the polyphenols present therein, against PCA. The epidemiological basis for this possibility is twofold. First, some epidemiological observations have suggested that people who consume tea regularly have a lower risk of PCA-related deaths. Second, the incidence of PCA in China, a population that consumes green tea on a regular basis, is lowest in the world.
Animals↗
Variceal ligation with bands and clips.
While endoscopic sclerotherapy is effective for management of variceal bleeding, significant local and systemic side effects promoted the development of alternative endoscopic therapies. Endoscopic band ligation has emerged as a technique with equal or greater efficacy and fewer local and systemic complications. New multibanded ligation systems have enhanced the speed and efficiency of endoscopic variceal ligation therapy and eliminated the need for an esophageal overtube. Endoscopic hemostatic clipping is another means of achieving directed, mechanical endoscopic hemostasis that has a limited role in variceal bleeding.
Acute Disease↗
Immunization coverage in three districts of North West Frontier Province (NWFP).
AIM: This community-based study was conducted to assess the progress of Expanded Programme on Immunization (EPI) in North West Frontier Province (NWFP) of Pakistan. METHOD: In this cross sectional survey, 120 randomly selected clusters in 03 districts of NWFP were included, 2673 children in the age group 12-35 months of 2583 randomly selected families were visited. RESULTS: The results showed that 65% of children were fully immunized, but out of them only half could be verified by immunization, need of 2nd and 3rd dose and no faith in immunization were the major causes of failure of immunization programme. Moreover, mother too busy, absence of vaccinator and inconvenient place of immunization were the obstacles pointed out by the parents. CONCLUSION: This study suggests the areas where improvement can be made to achieve the real target of immunization coverage. It is concluded that despite of more than 20 years of efforts by EPI, the ultimate objectives have not been achieved.
Child, Preschool↗
Effect of Momordica charantia (Karolla) extracts on fasting and postprandial serum glucose levels in NIDDM patients.
Effect of Momordica charantia, a bitter vegetable popularly known as Karolla, on fasting and post prandial (2 hours after 75 gm oral glucose intake) serum glucose levels were studied in 100 cases of moderate non-insulin dependent diabetic subjects. Drinking of the aqueous homogenized suspension of the vegetable pulp led to significant reduction (p < 0.001) of both fasting and post-prandial serum glucose levels. This hypoglycaemic action was observed in 86 (86%) cases. Five cases (5%) showed lowering of fasting serum glucose only.
Adult↗
Overexpression of ornithine decarboxylase in prostate cancer and prostatic fluid in humans.
Prostate cancer (PCA), the most commonly diagnosed cancer in males in the United States, is the second leading cause of cancer-related deaths of males in this country. Because of the poor success rate in the treatment of PCA, an intervention at an early stage may reduce the progression of small carcinoma to large metastatic lesion, thereby reducing PCA-related deaths. Concerted efforts are needed to establish mechanism-based approaches to develop: (a) the markers for early detection of the disease as well as toward monitoring the efficacy of treatment(s); and (b) novel chemopreventive strategies against PCA. Using unique samples of pair-matched benign and cancer tissue obtained from the same PCA patient, we showed that ornithine decarboxylase (ODC) activity is significantly (P < 0.001) elevated in PCA (1142 +/- 100; mean +/- SE) than in paired benign tissue (427 +/- 51; mean +/- SE). The immunoblot analysis also showed a significant elevation in the protein expression of ODC in the PCA tissues as compared with the paired benign tissue. Furthermore, our data showed that the ODC activity in the prostatic fluid obtained by a digital rectal massage from the patients with PCA (3847 +/- 162; mean +/- SE) was significantly higher than in the patients with benign prostatic hyperplasia (2742 +/- 167; mean +/- SE) or normal individuals (1244 +/- 67; mean +/- SE). This observation might be of significance because the prostatic fluid could be obtained noninvasively by digital rectal massage. We suggest that ODC could serve as a target for early detection of human PCA as well as for monitoring the efficacy of treatment(s). The development of ODC as a target for novel chemopreventive strategies against PCA is an intriguing possibility.
Biomarkers↗
Thermodynamic characterization of the conformational stability of the homodimeric protein, pea lectin.
The conformational stability of the homodimeric pea lectin was determined by both isothermal urea-induced and thermal denaturation in the absence and presence of urea. The denaturation profiles were analyzed to obtain the thermodynamic parameters associated with the unfolding of the protein. The data not only conform to the simple A2 if 2U model of unfolding but also are well described by the linear extrapolation model for the nature of denaturant-protein interactions. In addition, both the conformational stability (DeltaGs) and the DeltaCp for the protein unfolding is quite high, at about 18.79 kcal/mol and 5.32 kcal/(mol K), respectively, which may be a reflection of the relatively larger size of the dimeric molecule (Mr 49 000) and, perhaps, a consequent larger buried hydrophobic core in the folded protein. The simple two-state (A2 if 2U) nature of the unfolding process, with the absence of any monomeric intermediate, suggests that the quaternary interactions alone may contribute significantly to the conformational stability of the oligomer-a point that may be general to many oligomeric proteins.
Calorimetry, Differential Scanning↗
Delayed luteolysis after intra-uterine infusions of nordihydroguaiaretic acid in the ewe.
Intrauterine administration of nordihydroguaiaretic acid (5 mg, bid. NDGA), an inhibitor of the enzyme 5-lipoxygenase, on days 10-14 of the oestrous cycle, maintained luteal function and delayed oestrus in the ewe. The duration (mean +/- SD) of the oestrous cycle in the treatment group (n = 4) was 24 +/- 1 days, which was significantly (P < 0.001) longer than that of 16 +/- 1 days in vehicle-treated controls (n = 4); plasma progesterone concentrations were also significantly (P < 0.01) higher in the treatment group. On days 13 and 14 of the cycle (oestrus = Day 0) in the control group large pulses of 13,14-dihydro-15-keto prostaglandin F2alpha (PGFM) were evident, with mean (+/- SD) maximum concentrations of 232.5 +/- 66 and 415 +/- 309 pg ml(-1), respectively. In the treatment group, however, concentrations of PGFM were below detection level (< 50 pg ml(-1)). Similarly, in the control group, oxytocin release was highly pulsatile, with mean (+/- SD) peak concentrations of 21.8 +/- 5 and 18.5 +/- 6 pg ml(-1) on days 13 and 14, respectively; these were significantly (P < 0.01) higher than values of 7.6 +/- 3 and 6.1 +/- 3 pg ml(-1) in NDGA-treated ewes, where pulses were of relatively low amplitude. These results suggest that 5-lipoxygenase products of arachidonic acid metabolism may be involved in the positive feedback mechanism between luteal oxytocin and uterine PGF2alpha during luteolysis in the ewe.
Animals↗
Skin cancer chemopreventive effects of a flavonoid antioxidant silymarin are mediated via impairment of receptor tyrosine kinase signaling and perturbation in cell cycle progression.
Enhanced tyrosine kinase activity due to aberrant or overexpression of receptor and/or non-receptor tyrosine kinases has been implicated in a variety of human malignancies including cutaneous neoplasms. Epidermal growth factor receptor (EGFR)-mediated tyrosine phosphorylation may be a primary indicator of signal transduction regulating cell growth and proliferation. Recent studies have shown that skin tumor promoters such as phorbol ester and ultraviolet B radiation activate EGFR in mouse skin as well as in cell culture. Similarly, oxidative stress, which is implicated in skin tumor promotion, also activates EGFR-mediated cell signaling. Since this signaling pathway has been suggested to be involved in skin tumor promotion, its impairment by antioxidants may lead to an efficient way for skin cancer prevention and therapy. Recently, we showed that silymarin, a flavonoid antioxidant, affords exceptionally high to complete protection against several skin tumor promoters caused tumor promotion in mouse skin. Employing human epidermoid carcinoma cells A431 that contain overexpressed EGFR, in this study, we assessed whether the anti-skin tumor promoting effects of silymarin are due to its inhibitory effect on EGFR activation and down stream signaling pathway leading to perturbations in cell cycle progression. Treatment of cells with silymarin resulted in a significant inhibition of ligand-induced activation of EGFR with no change in its protein levels. Silymarin treatment also resulted in a significant decrease in tyrosine phosphorylation of Shc, an immediate downstream target of EGFR, but no change in the protein levels of Shc. The inhibition of EGFR activation by silymarin was associated with a highly significant to complete inhibition of EGFR intrinsic kinase activity. Cells treated with silymarin also showed a significant G2-M arrest in cell cycle progression, and a highly significant inhibition of DNA synthesis and cell growth in a dose-dependent manner. Taken together, these results suggest that skin cancer chemopreventive effects of silymarin are mediated via impairment of EGFR signaling which ultimately leads to perturbation in cell cycle progression resulting in the inhibition of proliferation and induction of growth arrest.
Animals↗
Photodynamic therapy results in induction of WAF1/CIP1/P21 leading to cell cycle arrest and apoptosis.
Photodynamic therapy (PDT) is a promising new modality that utilizes a combination of a photosensitizing chemical and visible light for the management of a variety of solid malignancies. The mechanism of PDT-mediated cell killing is not well defined. We investigated the involvement of cell cycle regulatory events during silicon phthalocyanine (Pc4)-PDT-mediated apoptosis in human epidermoid carcinoma cells A431. PDT resulted in apoptosis, inhibition of cell growth, and G0-G1 phase arrest of the cell cycle, in a time-dependent fashion. Western blot analysis revealed that PDT results in an induction of the cyclin kinase inhibitor WAF1/CIP1/p21, and a down-regulation of cyclin D1 and cyclin E, and their catalytic subunits cyclin-dependent kinase (cdk) 2 and cdk6. The treatment also resulted in a decrease in kinase activities associated with all the cdks and cyclins examined. PDT also resulted in (i) an increase in the binding of cyclin D1 and cdk6 toward WAF1/CIP1/p21, and (ii) a decrease in the binding of cyclin D1 toward cdk2 and cdk6. The binding of cyclin E and cdk2 toward WAF1/CIP1/p21, and of cyclin E toward cdk2 did not change by the treatment. These data suggest that PDT-mediated induction of WAF1/CIP1/p21 results in an imposition of artificial checkpoint at G1 --> S transition thereby resulting in an arrest of cells in G0-G1 phase of the cell cycle through inhibition in the cdk2, cdk6, cyclin D1, and cyclin E. We suggest that this arrest is an irreversible process and the cells, unable to repair the damages, ultimately undergo apoptosis.
Apoptosis↗
Involvement of nitric oxide during phthalocyanine (Pc4) photodynamic therapy-mediated apoptosis.
Photodynamic therapy (PDT), a new treatment modality, uses a combination of photosensitizing agent and visible light for the therapy of many solid malignancies. The hallmark of PDT is intracellular oxidative stress mediated by reactive oxygen species, which, through a cascade of events, results in a cell kill that induces apoptosis in some cells. To better understand the mechanism of apoptosis, we hypothesized the role of nitric oxide (NO), which is considered to be involved in a variety of physiological and pathological processes, during PDT. The model photosensitizer we have been working with is a silicon-phthalocyanine compound termed Pc4. Here, we investigated the involvement of NO during Pc4 PDT in PDT of apoptosis-resistant radiation-induced fibrosarcoma (RIF-1) cells and in PDT of apoptosis-sensitive human epidermoid carcinoma (A431) cells. Pc4 PDT resulted in a rapid increase in nitrite production in A431 cells, starting as early as 15 s post-PDT, and showed a progressive increase up to 15 min post-PDT. This increase in nitrite production was observed in cell lysates as well as in the cell culture medium. RIF-1 cells did not show an increase in nitrite production in either the cell lysates or the culture medium. At this time, a majority of the cells were viable. The Western blot analysis also showed a rapid increase in the expression of the constitutive form of NO synthase as early as 15 s post-PDT when compared to that of the controls. This response showed a dose dependency up to 5 min after Pc4 PDT. This observation was confirmed by a [3H]L-citrulline assay, which also showed a similar pattern for constitutive NO-synthase activity. RIF-1 cells did not show any change in protein expression or enzyme activity after the same treatment. These data, for the first time, demonstrate the generation of NO during PDT and suggest that it may be involved in PDT-mediated apoptosis. This may have relevance in improving the therapeutic efficacy of PDT using pharmacological modulators of NO or NO synthase.
Apoptosis↗
Alterations in cell cycle regulation in mouse skin tumors.
The connection between cell cycle and cancer has become obvious in as much as it is considered that dysregulated cellular proliferation is a hallmark of cancer. In many studies, the dysregulation of the cyclin-cdk-cki network has been reported in experimental animal and human tumors, but to our knowledge a complete profile of alterations in regulatory molecules in any tumor model system is lacking. In this study, we assessed the expression of various cyclins, cyclin dependent kinases, and cyclin kinase inhibitors in chemically induced squamous papillomas in SENCAR mouse skin. Western blot analysis data showed a significant upregulation of cyclins (31, 6, 19, and 12 folds elevation for cyclin-D1, D2, E, and A, respectively) in tumors compared to the normal skin. The protein expression of the cdk (1, 2, and 4) was also found to be elevated in tumors compared to normal skin (33 fold for cdk1, 14 fold for cdk2, and 9 fold for cdk4). In tumors, compared to the normal skin, a significant increase in the level of protein expression of p27 and p57 (4 and 3 fold, respectively) was evident. In normal skin, p16 and p21 were not detectable but significant expression of these proteins was detected in tumors. Taken together, these data provide evidence that cell cycle deregulation in G1-phase is a critical event during the course of two stage skin carcinogenesis. This may have relevance to epithelial cancers in general.
Animals↗
Impact of health service provision on mothers and infants in a rural village in North West Frontier Province, Pakistan.
OBJECTIVE: The objective of this paper is to examine the impact of the Health Service Research Project of the Pakistan Medical Research Council (PMRC) on mothers and infants in Budhni village, North West Frontier Province (NWFP), Pakistan. METHODS: Information from the PMRC records on the socioeconomic and demographic situation over the last 10 years and anthropometric measurements made on all infants from 1986-96 were collected and analysed. RESULTS: The demographic data showed a number of changes, namely a reduction in birth rate and improvements in perinatal, neonatal, infant and child mortality rates. Literacy in the village was poor (27 and 39% literate in 1986 and 1996, respectively) and female literacy showed no improvement (14%). Improvements in sanitation and in the water supply introduced by the PMRC had limited success, as clean water was subsequently contaminated by unclean hands and utensils, and 50% of the population continued to use open fields for sanitation. In 1986 only 27% of children 0-5 years were vaccinated, but by 1996, 96% of children had completed polio, diphtheria/pertussis/tetanus (DPT) and bacille Calmette-Guérin (BCG) vaccination programmes and 95% of women of child-bearing age were vaccinated against tetanus. Protection against tetanus reduced neonatal deaths and from 1993 onwards there have been no further cases. Anthropometric data for the period 1986-96 for infants (0-24 months) showed that at birth the majority of infants were close to the 50th National Centre for Health Statistics (NCHS) centile for weight and length, and only 5% of birth-weights were less than 2.5 kg. Growth charts showed faltering in length and weight and by 24-months length in both boys and girls was below the 3rd NCHS centile and weights were just above. CONCLUSIONS: Reductions in child mortality have occurred over the period 1986-96. However, the slow progress in adopting hygienic practices, despite health education, and the low literacy rates, particularly in women, may hamper continued improvement.
Adolescent↗