Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, a demand for therapy of higher usefulness in cancer patients has increased. We described in this paper a therapeutic modality which is based on SRC (self-rescuing concept) featuring dual activity, i.e., effect-enhancing activity and adverse reaction-reducing activity. We presented the theory and practice of S-1, a novel oral fluoropyrimidine anti-cancer agent designed to enhance anticancer activity and reduce gastrointestinal toxicity through the deliberate combination of the following components: an oral fluoropyrimidine agent tegafur; a DPD inhibitor (CDHP) which is more potent than uracil used in UFT; and an ORTC inhibitor (Oxo) which localizes in the gastrointestinal tract. S-1, as a combination drug with a molar ratio of 1:0.4:1 in FT, CDHP, and Oxo, respectively. A clinical pharmacology study to examine blood concentrations of 5-FU after twice-a-day administration of S-1 at a dose 40 mg/m2. Consequently , blood concentrations of 5-FU were 60 to 200 ng/m/ in all twelve patients examined. The overall response rate was 44.6% (45/101). In addition, the incidence of adverse reactions judged to be G3 or higher was 10% or less. Furthermore, we referred to combination therapy with 5-FU (CIV)(5-FU: 250 to 350 mg/body, 24-hour CVI, consecutive days) and low-dose cisplatin (CDDP: 3 to 5 mg/body, iv, 5 days/week) in which CDDP was used as modulator of 5-FU. Low-dose FP therapy provided response rates as high as 40 to 60% in 163 patients with sorts of gastrointestinal cancers except pancreas cancer. The incidence of adverse reactions which were judged to be G3 or higher was 2.5% (4/163) in nausea and vomiting. The incidences of other adverse reactions were 1% or less. And to the theory and practice of combination therapy with 5-FU (CVI) 24-hour CVI; 5-FU: 750 to 1000 mg/body/day on Monday, Wednesday, and Friday; withdrawal on Tuesday, Thursday, Saturday, and Sunday) intermittent administration and low-dose CDDP (3 to 5 mg/body/day day 1-5/w) consecutive administration in which a difference in cell cycle between gastrointestinal mucosal cel l and tumor cell or between bone marrow cell and tumor cell was utilized . Little adverse reactions, e.g., diarrhea and stomatitis, were observed despite the overall response rate which was as high as 52.4% (22/42). We intend in the future to combine the above mentioned therapeutic modalities provoking less adverse reactions and being gentle to patients with cancer in an effort to further increase their life expectancy.
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PMID:Conceptual changes in cancer chemotherapy--biochemical modulation of 5-FU from bench to clinic. 1089 55

The conventional concept in cancer chemotherapy considers that no efficacy can be attained without provoking adverse reactions. We presented concrete descriptions based on a novel concept allowing us to emerge from the old one. Relief of adverse reactions, e.g., diarrhea, stomatitis, anorexia, and H&F syndrome, not only improves QOL of the patient but also allows prolongation of the treatment period without lowering patient compliance. We describe in this paper a therapeutic modality which is based on SRC (self-rescuing concept) featuring dual activity, i.e., effect-enhancing activity and adverse reaction-reducing activity. We present the theory and practice of S-1, a novel oral fluoropyrimidine anticancer agent designed to enhance anticancer activity and reduce gastrointestinal toxicity through the deliberate combination of the following components: an oral fluoropyrimidine agent tegafur; a DPD inhibitor (CDHP) which is more potent than uracil used in UFT; and an ORTC inhibitor (Oxo) which localizes in the gastrointestinal tract. Furthermore, we refer to combination therapy with 5-FU (CIV) and low-dose consecutive CDDP in which CDDP was used as a modulator of 5-FU and to the theory and practice of combination therapy with 5-FU (CVI) intermittent (Monday, Wednesday, and Friday) administration and low-dose CDDP consecutive administration in which a difference in cell cycle between gastrointestinal mucosal cell and tumor cell or between bone marrow cell and tumor cell was utilized. We intend in future to combine the abovementioned therapeutic modalities provoking less adverse reactions and being gentle to patients with cancer in an effort to further increase their life expectancy.
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PMID:Conceptual changes in cancer chemotherapy: from an oral fluoropyrimidine prodrug, UFT, to a novel oral fluoropyrimidine prodrug, S-1, and low-dose FP therapy in Japan. 1108 68

A study on AIDS subjects carried out at the Calmette Hospital in Phnom-Penh between the 1st January 97 and the 30th December 98. The objective of this study was to describe the most frequent clinical manifestations as well as the opportunistic infections according to the 1993 CDC classification (purely clinical classification). Three hundred and fifty six AIDS patients hospitalized in medicine B were included in our study. A complete file was prepared for each subject, specifying his/her social and family situation, profession, sexual behavior and history. The clinical condition was specified and the paraclinical examinations were recorded. The average age was 35 years with 250 men and 106 women, i.e. a M/F sex ratio of 2.4. The majority of male contaminations were due to sexual relationships with multiple partners, 82%, and women with a single partner was of 78%. The use of condoms was of 60% (versus 40% occasional); the extent of drug-addiction was 1.12% (4 cases). A history of STD was found in 56% of cases. The presenting symptoms most frequently found were asthenia, anorexia, fever and weight-loss. In decreasing order, the clinical manifestations often associated were: weight-loss > 10% or a catechetic condition 58.70% (209/356), fever > 38 degrees C >1 month 53% (189/356), diarrhea (> one month) 41.60% (148/356). The most frequent opportunistic infections were: oral candidiasis 51.40% (183/356) and 40% are oro-oesophageal (oral candidiasis + dysphagia or odynphagia), pulmonary and extrapulmonary tuberculoses (TB) 43.50% (155/356) (pulmonary TB in 65.16%, TB of the lymph nodes 23.22% and disseminated TB and cerebral TB 11.61%), cryptococcal meningitis 11.80% (42/356) and pneumocystosis 6.50% (23/356), CMV retinitis 1.12% (4/356). The other opportunistic manifestations such as toxoplasmosis and Kaposis sarcoma are much more rarely encountered due to the difficulties of the paraclinical diagnosis. The mortality in the department was of 17.40% (62/356). In conclusions, tuberculosis is the most frequent of the opportunistic infections in Cambodia. Cryptococcal meningitis is in 3rd place for opportunistic infections. It is the first diagnosis that should be evoked in a meningeal irritation.
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PMID:[Clinical aspects of AIDS at the Calmette hospital in Phnom Penh, Kingdom of Cambodia A report on 356 patients hospitalized in the Medicine "B" Department of the Calmette Hospital]. 1131 28

Our objective was to determine the prevalence of HIV and the distribution of HIV-related diseases among adult, medical inpatients. Consecutive admissions were recruited and a single ELISA assay was used to determine HIV infection. Demographic and clinical details were extracted from clinical records. Of 507 patients, 54% were infected with HIV of which 84% had AIDS. HIV-infected patients were significantly younger (34.9 years) than uninfected patients (47.1 years) and had significantly higher risks for oral/oesophageal candidiasis (risk ratio [RR] 18.6), generalized lymphadenopathy (RR 7.1), unexplained fever (RR 7.0), chronic diarrhoea (RR 6.2) and pulmonary tuberculosis (RR 3.1). Pulmonary tuberculosis was present in 56% of HIV cases. Mortality was 22% for HIV cases and 9% (P=0.016) for others. The mean length of hospital stay was the same for HIV-infected and uninfected patients. AIDS is the most common reason for admission to adult medical wards and will increasingly limit the number of beds available for non-AIDS patients.
Int J STD AIDS 2001 Jun
PMID:Prevalence of HIV and HIV-related diseases in the adult medical wards of a tertiary hospital in Durban, South Africa. 1136 20

Human immunodeficiency virus (HIV) infection can weaken the immune system causing its inability to combat opportunistic infections. Managing the complexity of these opportunistic infections has created a challenge for healthcare professionals. Our knowledge on the aetiological agents causing opportunistic infections in immunocompromised hosts has increased over the last decade. Diarrhoeal diseases are frequent complications associated with HIV-infected patients. For most of the causes of diarrhoea, the clinical signs are non-specific, and the laboratory diagnostic workup is neither easy nor fast. This review provides data on aetiological approaches of common diarrhoeal diseases including viral, microbacterial, parasitic, bacterial and fungal infections, and HIV enteropathy; diagnostic evaluation; and treatment of diarrhoea in HIV-infected patients. This article will be helpful for those who are in the practice of managing diarrhoea in such patients.
Int J STD AIDS 2001 Oct
PMID:Management of diarrhoea in HIV-infected patients. 1156 29

Enteropathogenic Escherichia coli (EPEC) is a human-specific pathogen that causes severe diarrhoea in young children. The disease involves intimate interaction between the pathogen and the brush border of enterocytes. During infection, EPEC uses a type III secretion system (TTSS) to inject several proteins into the infected cells, and these effector proteins modify specific processes in the host cell. We show that, upon infection, EPEC induces detachment of the infected host cells from the substratum, modification of focal adhesions (FA) in the infected cells and specific dephosphorylation of focal adhesion kinase (FAK). We also show that EPEC-induced cell detachment is dependent on FAK expression by the infected cells. Finally, we demonstrate that cell detachment, FA modification and FAK dephosphorylation are dependent on functional TTSS in the infecting EPEC. These results suggest that EPEC is using its TTSS to inject protein(s) into the infected cells, which can induce FAK dephosphorylation, as well as FAK-dependent FA modification and cell detachment. These processes are specific and probably play an important role in EPEC virulence.
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PMID:Enteropathogenic Escherichia coli induces modification of the focal adhesions of infected host cells. 1195 40

The first case of HIV/AIDS in Morocco was notified in 1986. The Moroccan Ministry of Health has set up a system of management of HIV/AIDS cases and surveillance of the epidemic. Between 1991 and 1999, we studied 12,981 sera from patients in different Moroccan regions, who attended with high risk and/or symptoms of HIV/AIDS. The overall prevalence of positive HIV serology was 5.04% (4.67-5.44%). This rate was higher compared to blood donors which is 0.02%. From 1993 to 1998, the prevalence was around 4-5% (2.73-6.26%) then increased to 8.06% (6.89-9.36%) in 1999. Retrospective analysis of available epidemiological data have shown that the highest rate was observed in the South of Morocco with 12.23% (11.10-13.44%). Of the HIV positive cases, 72.22% of seropositives were infected heterosexually, 11.11% by intravenous drugs use, 7.41% by homosexuality, 4.63% by bisexuality and 4.63% and 0.62% by vertical transmission. The median age of infected persons was 33.3 years. Among documented HIV-positive individuals, 53.74% were aged 30-39 years, 21.43% were 20-29 years and 17.69% were 40 years or more. In this study, among HIV-positive patients 42.17% have loss of weight with fever and diarrhoea represent and 35.54% have loss of weight with fever, diarrhoea and opportunistic infections. The present work shows that the HIV infection increased significantly in 1999. Effective measures to control this trend should be implemented soon before the situation worsens.
Int J STD AIDS 2002 Dec
PMID:HIV epidemiology in Morocco: a nine-year survey (1991-1999). 1253 38

The aim of the study was to provide more comprehensive data on the clinical characteristics of hospitalized AIDS patients in Cambodia. Chart review of 381 HIV-infected patients admitted to a public hospital in Phnom Penh, Cambodia between December 1999 and May 2000 was performed. The in-hospital mortality rate was 43.6%. Approximately 50% of patients had two or more concurrent illnesses. Very advanced HIV disease was common, with CD4 cell counts below 10 cells/mm(3) in 43.2%. Only 28.3% of the patients had documentation of their HIV infection prior to hospitalization. Chronic diarrhoea was the most frequent opportunistic illness (41.2%), followed by tuberculosis (26%), cryptococcal meningitis (12.6%), Pneumocystis carinii pneumonia (8.4%), and encephalitis (4.7%). Chronic diarrhoea and tuberculosis were the most important opportunistic infections observed in HIV-infected hospitalized patients in Cambodia. These findings illustrate the need for early diagnosis of HIV-infection, effective prophylaxis for opportunistic infections and improved access to antiretroviral therapy in Cambodia.
Int J STD AIDS 2003 Jun
PMID:Spectrum of opportunistic infections in hospitalized HIV-infected patients in Phnom Penh, Cambodia. 1281 70

Differentiation between abacavir hypersensitivity and viral respiratory infections is problematic. Fifteen cases of abacavir hypersensitivity were matched to 30 controls with culture proven influenza A with no abacavir exposure. Rash was associated with hypersensitivity (odds ratio [OR] = 13.1, P = 0.02) as was the presence of nausea (OR = 30, P < 0.001), vomiting (OR = 17.1, P = 0.001) or diarrhoea (OR = 22, P < 0.001). The number of gastrointestinal symptoms was also predictive of hypersensitivity reaction (P < 0.001). Respiratory symptoms (cough, sore throat, or dyspnoea) were not associated with abacavir hypersensitivity (OR = 0.08, P = 0.001). Multivariate analysis confirmed the following associations for abacavir hypersensitivity: the number of gastrointestinal symptoms (OR = 8.6, P = 0.0032), cough (OR = 0.039, P = 0.02) and rash (OR = 16.9, P = 0.07). Abacavir hypersensitivity is strongly associated with gastrointestinal (GI) symptoms. Cough without GI symptoms is associated with influenza.
Int J STD AIDS 2003 Jul
PMID:Comparison of symptoms of influenza A with abacavir-associated hypersensitivity reaction. 1286 29

A cross sectional survey was conducted to determine the association between enteric parasites and diarrhoea in HIV-infected adults in Caracas. Three hundred and four patients were evaluated: 104 had acute diarrhoea, 113 chronic diarrhoea and 87 were controls. Isopora belli infection was associated with acute (P = 0.022) and chronic diarrhoea (P = 0.003), Entamoeba histolytica/dispar infection was also associated with both acute (P = 0.015) and chronic diarrhoea (P = 0.017). Strongyloides stercoralis (P = 0.003), and Cryptosporidium parvum (P = 0.017) infections were associated mainly with chronic episodes. Weight loss (P < 0.001), a non-infectious factor investigated, was significantly associated with diarrhoea. Eosinophilia, a laboratory parameter studied, was found to be associated with strongyloidiasis (P = 0.001), giardiasis (P = 0.001) and isoporiasis (P = 0.003). In summary, the presence of enteric parasites in HIV-infected patients from tropical urban areas with diarrhoea, with or without significant weight loss, must be considered. Similarly, eosinophilia might suggest parasitic infection in these patients.
Int J STD AIDS 2003 Jul
PMID:Association between parasitic intestinal infections and acute or chronic diarrhoea in HIV-infected patients in Caracas, Venezuela. 1286 31


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