Studying the Impact of Presence of Alpha Acid Glycoprotein and Protein Glycoprotein in Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate in the State of Qatar.

Despite the efficacy of imatinib mesylate (IM) in treating chronic myeloid leukemia (CML), there is a high degree of resistance. Alpha- 1-acid glycoprotein may reduce drug efficacy through its ability to interact with IM and blocks it from reaching its target, while protein glycoprotein (PGP) may reduce the intracellular concentration of the drug via an active pump mechanism. We thus investigated the correlation between AGP and PGP levels and the resistance/response to treatment. A total of 26 CML patients were investigated for AGP and PGP levels at diagnosis and during treatment. There was no significant difference or correlation between AGP levels and the different groups of patients. There was also no significant difference in the fluorescence intensities of PGP levels among the different patient groups. The resistance observed in our CML patient population could not be correlated with AGP and PGP levels. There was no significant pattern of AGP and PGP expression, irrespective of the response or resistance to treatment.

Effects of seated and standing cold water immersion on recovery from repeated sprinting.

This study investigated the effects of two different hydrostatic pressures (seated or standing) during cold water immersion at attenuating the deleterious effects of strenuous exercise on indices of damage and recovery. Twenty four male well-trained games players (age 23 ± 3 years; body mass 81.4 ± 8.7 kg: [Formula: see text]O2max 57.5 ± 4.9 ml∙kg(-1)∙min(-1)) completed the Loughborough Intermittent Shuttle Test (LIST) and were randomly assigned to either a control, seated cold water immersion or a standing cold water immersion (14 min at 14°C). Maximal isometric voluntary contraction, counter-movement jump, creatine kinase, C-reactive protein, interleukin-6 and delayed onset muscle soreness (DOMS) were measured before and up to 72 h following the LIST. All dependent variables showed main effects for time (P < 0.05) following the LIST, indicating physiological stress and muscle damage following the exercise. There were no significant group differences between control and either of the cold water immersion interventions. Seated cold water immersion was associated with lower DOMS than standing cold water immersion (effect size = 1.86; P = 0.001). These data suggest that increasing hydrostatic pressure by standing in cold water does not provide an additional recovery benefit over seated cold water immersion, and that both seated and standing immersions have no benefit in promoting recovery following intermittent sprint exercise.

Recovery and adaptation from repeated intermittent-sprint exercise.

PURPOSE: This investigation aimed to ascertain a detailed physiological profile of recovery from intermittent-sprint exercise of athletes familiar with the exercise and to investigate if athletes receive a protective effect on markers of exercise-induced muscle damage (EIMD), inflammation, and oxidative stress after a repeated exposure to an identical bout of intermittent-sprint exercise. METHODS: Eight well-trained male team-sport athletes of National League or English University Premier Division standard (mean ± SD age 23 ± 3 y, VO2max 54.8 ± 4.6 mL ·kg-1 · min-1) completed the Loughborough Intermittent Shuttle Test (LIST) on 2 occasions, separated by 14 d. Maximal isometric voluntary contraction (MIVC), countermovement jump (CMJ), creatine kinase (CK), C-reactive protein (CRP), interleukin-6 (IL-6), F2-isoprostanes, and muscle soreness (DOMS) were measured before and up to 72 h after the initial and repeated LISTs. RESULTS: MIVC, CMJ, CK, IL-6, and DOMS all showed main effects for time (P < .05) after the LIST, indicating that EIMD was present. DOMS peaked at 24 h after LIST 1 (110 ± 53 mm), was attenuated after LIST 2 (56 ± 39 mm), and was the only dependent variable to demonstrate a reduction in the second bout (P = .008). All other markers indicated that EIMD did not differ between bouts. CONCLUSION: Well-trained games players experienced EIMD after exposure to both exercise tests, despite being accustomed to the exercise type. This suggests that well-trained athletes receive a very limited protective effect from the first bout.

Nigella sativa concoction induced sustained seroreversion in HIV patient.

Nigella sativa had been documented to possess many therapeutic functions in medicine but the least expected is sero-reversion in HIV infection which is very rare despite extensive therapy with highly active anti-retroviral therapy (HAART). This case presentation is to highlight the complete recovery and sero-reversion of adult HIV patient after treatment with Nigella sativa concoction for the period of six months. The patient presented to the herbal therapist with history of chronic fever, diarrhoea, weight loss and multiple papular pruritic lesions of 3 months duration. Examination revealed moderate weight loss, and the laboratory tests of ELISA (Genscreen) and western blot (new blot 1 & 2) confirmed sero-positivity to HIV infection with pre-treatment viral (HIV-RNA) load and CD4 count of 27,000 copies/ml and CD4 count of 250 cells/ mm(3) respectively. The patient was commenced on Nigella sativa concoction 10 mls twice daily for 6 months.. He was contacted daily to monitor side-effects and drug efficacy. Fever, diarrhoea and multiple pruritic lesions disappeared on 5th, 7th and 20th day respectively on Nigella sativa therapy. The CD4 count decreased to 160 cells/ mm3 despite significant reduction in viral load (≤1000 copies/ml) on 30th day on N. sativa. Repeated EIA and Western blot tests on 187th day on Nigella sativa therapy was sero-negative. The post therapy CD4 count was 650 cells/ mm(3) with undetectable viral (HIV-RNA) load. Several repeats of the HIV tests remained sero-negative, aviraemia and normal CD4 count since 24 months without herbal therapy. This case report reflects the fact that there are possible therapeutic agents in Nigella sativa that may effectively control HIV infection.

A mixed exercise training programme is feasible and safe and may improve quality of life and muscle strength in multiple myeloma survivors.

BACKGROUND: Exercise programmes are beneficial for cancer patients however evidence is limited in patients with multiple myeloma (MM), a cancer that is characterised by osteolytic bone disease, giving rise to high levels of bone morbidity including fractures and bone pain. METHODS: We conducted a single arm phase 2 study of an exercise programme (EP) as rehabilitation for treated MM patients, to evaluate feasibility, effects on QOL and physiological parameters. Patients were given individualised programmes, comprising stretching, aerobic and resistance exercises, carried out under supervision for 3 months then at home for a further 3 months. RESULTS: Study uptake was high, 60 of 75 (80%) patients approached consented to the study. Screen failures (11, due to fracture risk and disease relapse) and patient withdrawals (12) resulted in a final 37 patients enrolling on the programme. These 37 patients demonstrated high attendance rates in the supervised classes (87%), and high levels of adherence in home exercising (73%). Patients reported better QOL following the EP, with improvement in FACT-G and Fatigue scores over time from baseline (p<0.01 for both, one-way repeated measures ANOVA) to 6 months. Upper and lower limb strength also improved on the EP, from baseline to 6 months (p<0.01 for both). There were no adverse reactions. CONCLUSIONS: An EP in MM patients is feasible and safe, with high attendance and adherence. Benefits in QOL, fatigue and muscle strength await confirmation in randomized studies, prompting urgent evaluation of the benefits of EP in the rehabilitation of MM patients.

Prevalence, sociodemographic characteristics and risk factors for hepatitis C infection among pregnant women in Calabar municipality, Nigeria.

BACKGROUND AND AIMS: The epidemiology and risk factors for hepatitis C virus (HCV) infection in developing countries where intravenous drug use (IDU) is uncommon its poorly understood. This study therefore aims to determine the prevalence of HCV and its associated risk factors among pregnant women in Calabar municipality. METHODS: A total of 506 out of 716 antenatal care (ANC) patients seen at the General Hospital, Mary Slessor Avenue, Calabar between August and November 2005 and the University of Calabar Teaching Hospital (UCTH) between October and November 2005 were evaluated for their HCV status using the One Step HCV Test kit (Binomial diagnostics, UK), with reference to the subjects' demographic and behavioural risk factors. RESULTS: HCV prevalence was determined to be 0.4% (2/506) and was only seen in women aged 38 years and over. Histories of blood transfusion, surgery, involvement in polygamous marriage, sharing of a toothbrush and female circumcision were all non-significant risk factors for the infecion. CONCLUSIONS: This study reveals a low HCV prevalence among pregnant women in Calabar municipality with no identifiable risk factor. The study calls for a re-evaluation of the transmission modes of HCV especially in developing countries where intravenous drug use is rare.

TIS11 family proteins and their roles in posttranscriptional gene regulation.

Posttranscriptional regulation of gene expression of mRNAs containing adenine-uridine rich elements (AREs) in their 3' untranslated regions is mediated by a number of different proteins that interact with these elements to either stabilise or destabilise them. The present review concerns the TPA-inducible sequence 11 (TIS11) protein family, a small family of proteins, that appears to interact with ARE-containing mRNAs and promote their degradation. This family of proteins has been extensively studied in the past decade. Studies have focussed on determining their biochemical functions, identifying their target mRNAs, and determining their roles in cell functions and diseases.

SEMG-1 expression in early stage chronic lymphocytic leukemia.

BACKGROUND AIMS: Chronic lymphocytic leukemia (CLL) is an indolent disease. It is currently recommended that patients with CLL stages 0 and I follow a watchful waiting strategy. These patients are, therefore, a suitable group for testing immunotherapeutic approaches to avoid problems of immunosuppression as a result of disease progression and chemotherapy. In this study, we investigated the expression of SEMG-1 in early CLL to determine the suitability of SEMG-1 as a target for further development of tumor vaccines for early CLL. METHODS: A combination of reverse transcriptase (RT)-polymerase chain reaction (PCR) and immunocytochemistry was used to evaluate the expression of SEMG-1 in early CLL. The results were correlated with Zap 70 expression. Recombinant SEMG-1 protein was used in an enzyme-linked immunosorbent assay (ELISA) to determine the presence of SEMG-1 antibodies (Ab) in serum from these patients. RESULTS: The SEMG-1 gene was expressed in 19/41 (46%) patients with early CLL. Gene expression was associated with protein synthesis in CLL cells. Protein expression, however, was heterogeneous within individual patients. Only transcripts encoding the SEMG-1(50) variant and not SEMG-1(43) were detected. SEMG-1(50) was expressed irrespective of the Zap 70 status. High-titer SEMG-1 IgG but not IgM Ab were detected in some of these patients, suggesting that SEMG-1-reactive immune responses are intact within the immune repertoire of early CLL patients. CONCLUSIONS: SEMG-1 is expressed in nearly half of patients with early CLL and may be a target for further investigations into its use for immunotherapy of early CLL.

Identification of protamine 1 as a novel cancer-testis antigen in early chronic lymphocytic leukaemia.

Early chronic lymphocytic leukaemia (CLL) is an ideal disease for immunotherapy. We previously showed that SEMG 1 is a cancer-testis (CT) antigen in CLL. In this study, SEMG 1 was applied as the bait in a yeast two-hybrid system of a testicular cDNA library. Seven clones were isolated and Protamine (Prm) 1 was identified as a novel CT antigen in early CLL. PRM1 transcripts were detected in 11/41 (26.8%) patients. Prm 1 protein was also expressed but heterogeneously within individual patients. Of the 11 patients expressing Prm 1, four expressed Zap 70 protein and seven did not. These results, therefore, indicate that Prm 1 could potentially be a suitable target for the design of tumour vaccine for patients with early CLL, including for those with poor risk CLL. High titres of Prm 1 IgG antibodies could be detected in 20 of these 41 CLL patients but not in any of the 20 healthy donors (P = 0.0001), suggesting the presence of Prm 1-reactive immune responses within the immune repertoire of patients with early CLL. Further work is warranted, especially in approaches to upregulate Prm 1 expression, and to determine the role of Prm 1 as an immunotherapeutic target for early CLL.

The use of Complementary and Alternative Medicine by cancer patients.

The use of Complementary and Alternative Medicine (CAM) among cancer patients is widespread and appears to be increasing. However, it is not clear whether patients use CAM as an 'alternative' to standard oncology care or as an adjunct to the conventional treatment they receive. This study reviews the role of CAM therapies in the management of cancer, from the view of both patients and health professionals and it highlights issues relating to the efficacy of CAM used by cancer patients. Most patients use CAM to 'complement' the conventional therapies of radiotherapy, chemotherapy, hormone therapy and surgery. Health professionals in general have expressed positive views when CAM is used 'complementarily' and not as an 'Alternative'. Results so far published have shown that CAM can contribute to improving the quality of life of cancer patients and their general well-being.

Cancer-testis antigens in haematological malignancies.

Immunotherapy is an attractive therapeutic option for patients with haematological malignancies. Until recently, the progress in the development of tumour vaccines for haematological malignancies had been slow due to the lack of suitable targets. Cancer-testis (CT) antigens are potentially suitable molecules for tumour vaccines of haematological malignancies because of their high immunogenicity in vivo and their relatively restricted normal tissue distribution. This review evaluates the properties and potential functions of CT antigens. We discuss the expression of CT antigens in patient with haematological malignancies and provide evidence in support of their immunogenicity in vivo in these patients. We also address the role of 'epigenetic' regulation of CT antigens in haematological malignancies and how hypomethylating agents could induce the expression of some of these antigens in tumour cells to overcome the problem of heterogeneity of expression of the antigen within individual tumour specimens. Data implicating the interaction of the promoter genes of some of these CT antigens with the MeCP2 protein also suggest the potential role of the histone deacetylase inhibitors in inducing antigen expression in tumour cells. Finally, we discuss the direction of future research in advancing the development of tumour vaccines for haematological malignancies.

IL-1 does not reverse the anti-proliferative effect of aspirin in breast cancer cells.

OBJECTIVES: Interleukin-1 (IL-1) is a multifunctional proinflammatory cytokine. There have been studies suggesting a role in affecting growth and invasiveness of malignant breast cells by either blocking or stimulating growth of cultured MCF-7 breast cancer cells. This effect may be mediated by induction of COX-2. Aspirin is an inhibitor of COX-2 and has been implicated, with other non-steroidal anti-inflammatory drugs (NSAIDS) in prevention and treatment of breast cancer. In this study the in vitro effects of IL-1 and aspirin on growth of MCF-7 human breast cancer cells was examined. METHODS: MCF-7 cells were treated with various concentrations of IL-1 and aspirin alone and in combination. Cell growth was assessed by cell number measurement. RESULTS: Aspirin significantly decreased growth rate in a dose-dependent manner, alone and as a combined treatment with IL-1 with a maximum reduction in growth rate at 300 mg/ml (P < 0.05). Treatment with IL-1 alone showed no significant effect on growth rate of MCF-7 cells (P > 0.05). CONCLUSION: This study confirms that aspirin suppresses the proliferation rate of MCF-7 cells both as a single agent and in combination with IL-1. It also suggests that IL-1 alone does not stimulate or inhibit growth of MCF-7 cells.

Hepatocellular Carcinoma in The Gambia and the role of Hepatitis B and Hepatitis C.

OBJECTIVES: Hepatocellular Carcinoma is the commonest form of cancer in The Gambia, and although Hepatitis B and Hepatitis C are known risk factors, accurate baseline data on Hepatitis B and Hepatitis C distribution in the region are limited. Similarly data including information on the involvement of the viruses in HCC remains unknown. The current study was undertaken to estimate the risk of HCC in relation to HCV and HBV in The Gambia. METHODS: Thirteen patients with histological proven history of HCC and 39 healthy controls were enrolled in the study. Each subject blood was screened individually for anti-HCV using ORTHO HCV 3.0 ELISA test system (Ortho-Clinical Diagnostics, Inc, U.S.A) and for HBsAg using QUADRATECH CHECK 4-HBs one step generation hepatitis B surface antigen test kit (VEDALAB, France) following the manufacturers instructions. RESULTS: HBsAg and anti-HCV was detected in 38.5 % (5/13) and 7.7% (1/39) of the persons with a history of HCC respectively. HBsAg but not anti-HCV was detected in 12.8% (5/39 of the case control subjects. HBsAg and HCV rates among the HCC patients were higher in men than women. Rates were highest in patients 48 years and above (37.5%; 3/8). No patient was found with anti-HCV and anti-HBV. CONCLUSION: These results indicate that the involvement of HBV and HCV in HCC in the country is in a ratio of 5:1 and that these two viruses might be independently involved in the pathogenesis of the disease. The study revealed a statistically significant association (p = 0.04) between HBsAg and HCC patients. The results also indicate that up to 50% of HCC cases in the country may be due to non viral factors and calls for further studies in this regard. These findings call for provision of diagnostic facilities for these viruses in hospitals and for their routine screening in blood banks while intervention programmes should be put in place.

Exercise for breast cancer survival: the effect on cancer risk and cancer-related fatigue (CRF).

To date, all epidemiological research in this area has focused on the relationship between physical activity level and the risk of breast cancer in healthy women, or more recently, those who have recovered from the disease. Most of this research highlights the fact that those women who are physically active are at a reduced risk of the disease. Although physical activity is similar to exercise, it lacks the specificity of a prescribed exercise training program. Consequently, such research can only be viewed as a promising indicator of the beneficial effect that regular exercise may have for breast cancer survivors. Furthermore, due to the nature of such research, there has been a failure to provide specific evidence concerning the most suitable modality, duration, intensity, and frequency of training for risk reduction in breast cancer survivors. Thus, evidence aiding the correct prescription of exercise for this population has been lacking. More promising evidence is provided by randomized controlled trials, which examine the effect of exercise on specific risk factors and provide convincing scientific rationale for the use of exercise among breast cancer survivors. These studies not only provide understanding of the physiological mechanisms by which exercise can be effective at aiding a reduction in breast cancer risk, but also allow conclusions on the correct prescription to be drawn. Additionally, exercise has proven to be effective in combating cancer-related fatigue (CRF), significantly improving both quality of life outcomes (QOL) and physiological capacity in women who have survived breast cancer. In order to promote a wider understanding of the beneficial effect that exercise holds for this population regarding reduction of breast cancer risk and CRF, this review discusses this research, making conclusions regarding the necessary training prescription to elicit such benefits.

Elevated expression of cyclooxygenase-2 in breast cancer and ductal carcinoma in situ has no correlation with established prognostic markers.

BACKGROUND AND OBJECTIVES: Elevated expression of cyclooxygenase-2 (COX-2) has been established to be a feature of breast cancer. There has been inconsistency in the literature regarding the precise significance of this-some studies have found no clinicopathological relevance at all, whilst others have concluded COX-2 expression is an important biomarker in invasive disease and pre-cancerous lesions, correlating with poor prognostic features. We studied COX-2 expression in invasive ductal cancer (IDC) specimens and ductal carcinoma in situ (DCIS) in order to clarify these issues. METHOD: Archival specimens of IDC and DCIS (n = 39) were stained with a polyclonal antibody to COX-2. Results were correlated with recognised clinicopathological parameters. RESULTS: COX-2 expression occurred in 36.7% of IDCs and 54.5% of DCIS lesions. There was no correlation between increased expression and any clinicopathological features. COX-2 expression did not occur in adjacent non-cancerous tissue (ANCT). CONCLUSION: We have confirmed that COX-2 expression does occur in invasive cancers, in DCIS, and is not associated with established prognostic markers. The presence of COX-2 expression in DCIS and invasive cancers has positive implications for the future prevention and treatment of breast cancer with COX-2 inhibitors. A large proportion of tumours are, however, COX-2 negative and may be poor candidates for COX-2 suppression.

Evaluation of the Taguchi methods for the simultaneous assessment of the effects of multiple variables in the tumour microenvironment.

BACKGROUND: The control of proliferation, differentiation and survival of normal and malignant cells in the tumour microenvironment is under the control of a wide range of different factors, including cell:cell interactions, cytokines, growth factors and hormonal influences. However, the ways in which these factors interact are poorly understood. In order to compare the effects of multiple variables, experimental design becomes complex and difficult to manage. We have therefore evaluated the use of a novel approach to multifactorial experimental design, the Taguchi methods, to approach this problem. METHOD: The Taguchi methods are widely used by quality engineering scientists to compare the effects of multiple variables, together with their interactions, with a simple and manageable experimental design. In order to evaluate these methods, we have used a simple and robust system to compare a traditional experimental design with the Taguchi Methods. The effect of G-CSF, GM-CSF, IL3 and M-CSF on daunorubicin mediated cytotoxicity in K562 cells was measured using the MTT assay. RESULTS: Both methods demonstrated that the same combination of growth factors at the same concentrations minimised daunorubicin cytotoxicity in this assay. CONCLUSIONS: These findings demonstrate that Taguchi methods may be a valuable tool for the investigation of the interactions of multiple variables in the tumour microenvironment.

Elevated cyclooxygenase-2 expression correlates with distant metastases in breast cancer.

BACKGROUND: Cyclooxygenase-2 (COX-2) overexpression clearly plays an important role in the pathogenesis of breast cancer. In this study, we analysed the relationship between COX-2 expression and various clinicopathological factors in human breast cancer. MATERIALS AND METHODS: Using immunohistochemistry, we analysed archival specimens of human breast cancer (n=29) using antibodies to COX-2, ER, PgR and HER2 and, from medical records, obtained clinicopathological data. RESULTS: We observed a significant association between COX-2 overexpression and distant metastasis. COX-2 expression was not significantly associated with any other clinical or pathological variable. CONCLUSION: These findings lend support to the hypothesis that COX-2 overexpression represents an adverse prognostic event in human breast cancer and are encouraging for proposed strategies of COX-2 suppression to treat the disease.

Cytotoxic CD4+ T cells in patients with B cell chronic lymphocytic leukemia kill via a perforin-mediated pathway.

BACKGROUND AND OBJECTIVES: B-cell chronic lymphocytic leukemia (B-CLL) is a clonal expansion of CD5+B cells that accumulate due to their uncontrolled growth and resistance to apoptosis. We have previously shown that up to 50% of blood CD4+ T cells in B-CLL patients have a cytotoxicity-related CD28- CD57+ phenotype and high content of both granzyme B and perforin (PF). In this study we investigate the cytotoxic potential of these cells against autologous B-CLL cells. DESIGN AND METHODS: Blood CD4+ or CD8+ T cells were positively isolated from B-CLL patients and cultured under a range of conditions with autologous purified B-CLL cells and with bispecific [anti-CD3 x anti-CD19] antibodies. Apoptosis of labeled B-CLL cells was assessed using the change of mitochondrial membrane potential with the fluorescent dye DiOC6 and confirmed by annexin V binding. RESULTS: There was time- and dose-dependent killing of B-CLL cells by both CD8+ and CD4+ T cells and this ranged from 6.6 - 68.0% for CD4+ cells and 6.4 - 57.8% for CD8+ cells. Almost complete inhibition by concanamycin A suggests that CD4+ T cells like CD8+ T cells induced apoptosis through a perforin-mediated pathway, but not via Fas/FasL (as indicated by lack of blocking with brefeldin A), tumor necrosis factor alpha or TRAIL. INTERPRETATION AND CONCLUSIONS: This study shows that blood CD4+PF+ T cells enriched in B-CLL patients, are able to kill autologous B-CLL cells ex vivo, through bispecific antibodies via a perforin mediated mechanism.

Role of apoptosis in the pathogenesis of B-cell chronic lymphocytic leukaemia.

B-cell chronic lymphocytic leukaemia (B-CLL) is a clinically heterogeneous disease characterised by the accumulation of a clonal population of B lymphocytes. This accumulation is considered to result from the prolonged survival of B-CLL cells arrested in the G0 stage of the cell cycle. However, when cultured in vitro, B-CLL cells die rapidly by apoptosis. It is now clear that a number of factors can delay or postpone the onset of apoptosis, including a number of cytokines and direct contact with different cell types. Although many drugs are now known to cause clinical improvement in B-CLL by causing apoptosis of B-CLL cells, in only a few cases have biological mechanisms been reported to have similar effects. It is now important to understand the role of these mechanisms in the pathogenesis and progression of B-CLL, and to devise strategies to exploit them for therapeutic use.