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Pathogenesis and treatment of gastric carcinoma: "an up-date with brief review"

Khan FA, Shukla AN

J Cancer Res Ther, 2007 11 14;2(4):196-9.
PMID: 17998703

Gastric cancer is one of the most common cancers and most frequent causes of cancer-related deaths in the world. The overall survival rate is 15-20%. Although the incidence is declining, its prognosis remains poor. The etiological factors and pathogenesis of gastric cancer are not yet fully understood. The integrated research in molecular pathology clarified the details of genetic and epigenetic abnormalities of cancer-related genes in the course of development and progression of gastric cancer. Although epidemiological evidences indicate that environmental factors play a major role in the carcinogenesis, the role of immunological, genetic and immunogenetic factors are thought to contribute to etiopathogenesis of gastric carcinoma. In addition to better understanding of pathogenesis of gastric cancer, the incidence, diagnostic studies and the therapeutic options have also undergone important changes in the last decade. There is ongoing debate regarding the role of adjuvant treatment. In advanced disease, palliation of symptoms, rather than cure, is the primary goal of patient management. Several combination therapies have been developed and have been examined in phase III trials; however, in most cases, they have failed to demonstrate a survival advantage over the reference arm. This review summarizes the newer concepts of molecular biology on gastric carcinogenesis and the new important recommendations for the management of patient with gastric carcinoma.

Matched MeSH terms: Clinical Trials as Topic
Chemoprevention of colorectal cancer with nonsteroidal anti-inflammatory drugs

Hilmi I, Goh KL

Chin J Dig Dis, 2006;7(1):1-6.
PMID: 16412030 DOI: 10.1111/j.1443-9573.2006.00236.x

Colorectal carcinoma is one of the commonest solid organ tumors in the world and its prevalence appears to be increasing in Asia. Recently, there has been much interest in various chemotherapeutic agents for the management of this condition, in particular nonsteroidal anti-inflammatory drugs (NSAIDs). There is a large amount of data that suggest traditional NSAIDs, as well as the new cyclooxygenase (COX)-2 selective inhibitors such as rofecoxib and celecoxib, have a role in the setting of primary and secondary prevention, and adjuvant therapy of both sporadic colorectal carcinoma and familial adenomatous polyposis. This review examines some of this data, as well as the potential problems and limitations of using these agents, particularly in light of the recent withdrawal of rofecoxib.

Matched MeSH terms: Clinical Trials as Topic
Fulltext Patent foramen ovale and migraine: what is the relationship between the two?

Sathasivam S, Sathasivam S

J Cardiol, 2013 Apr;61(4):256-9.
PMID: 23484805 DOI: 10.1016/j.jjcc.2012.12.005

There is conflicting evidence on the causal relationship of patent foramen ovale (PFO) in migraine. This review will examine the pathophysiological relevance of PFO in migraine, the epidemiological evidence of PFO causing migraine, and the existing evidence on the effectiveness of closure of PFO on the symptomatology of migraine. From the current available evidence, the role of PFO in migraine is debatable, and interventions such as closure of PFO cannot yet be considered routine treatment of migraine.

Matched MeSH terms: Clinical Trials as Topic
Anti-inflammatory, antibacterial and analgesic potential of cocos nucifera linn.: a review

Dua K, Sheshala R, Ling TY, Hui Ling S, Gorajana A

Antiinflamm Antiallergy Agents Med Chem, 2013;12(2):158-64.
PMID: 23286236

At present, approximately 25%of drugs in modern pharmacopoeia are derived from plant sources (phytomedicines) that can be developed for the treatment of diseases and disorders. Many other drugs are synthetic analogues built on the prototype compounds isolated from plants. Cocos nucifera Linn. (Arecaceae), which is commonly known as coconut, is a plant possessing a lot of potential as an ingredient in traditional medicines for the treatment of metabolic disorders and particularly as an anti-inflammatory, antimicrobial and analgesic agent. This review emphasizes on the recent literature and research findings that highlight the significant biological activities of C. nucifera Linn. such as its anti-inflammatory, antimicrobial and analgesic properties. This review can help researchers keen on exploiting the therapeutic potential of C. nucifera Linn. which may motivate them to further explore their commercial viability.

Matched MeSH terms: Clinical Trials as Topic
Fulltext ALLHAT in perspective: implications to clinical practice and clinical trials

Yusoff K

Med J Malaysia, 2005 Jun;60(2):239-45.
PMID: 16114170

ALLHAT study is the biggest randomized clinical trial in hypertension ever conducted. Its objective was to ompare the efficacy of newer (calcium channel blocker amlodipine and angiotensin-converting enzyme inhibitor inopril) to the older (diuretic chlorthalidone) antihypertensive agents in the treatment of patients with hypertension. After enrolling 42,000 patients who were followed for an average of 4.9 years, ALLHAT did not find significant differences in the primary end-points between these antihypertenive agents. ALLHAT however found significant differences in the secondary end-points such as heart failure and strokes between chlorthalidone and amlodipine or lisinopril. Based on these and on economic reasons, the investigators unequivocally recommended diuretics as the first line therapy for hypertension. Since its publication, ALLHAT has been much discussed, debated A and opined. The choice of drugs for study, the study design, the conduct of the study and the conclusions drawn by the investigators had all been criticised or controversial. Yet ALLHAT has been widely quoted, commented upon or referred to and it has been instrumental in initiating the JNC VII Guidelines. Thus a thorough understanding of ALLHAT is necessary for clinical practice and in designing and evaluating clinical trials in the future. Moving Points: in Medicine will capture the essence of ALLHAT, discusses its implications to clinical trials and explores its possible impact on the practice of medicine in this country.

Matched MeSH terms: Clinical Trials as Topic
Fulltext Status of research and development of vaccines for enterovirus 71

Reed Z, Cardosa MJ

Vaccine, 2016 06 03;34(26):2967-2970.
PMID: 26973065 DOI: 10.1016/j.vaccine.2016.02.077

Although outbreaks of Hand, Foot, and Mouth Disease (HFMD) in young children have long been recognized worldwide, the occurrence of rare and life-threatening neurological, respiratory, and cardiac complications has propelled this common condition into the spotlight as a major public health problem in the affected countries. Various enteroviruses cause HFMD, but the severe complications have been mostly associated with enterovirus 71 (EV71). Medical treatment is supportive and measures to interrupt transmission have been challenging to implement. Preventive vaccines could have an important clinical impact, especially among children younger than 3 years old who are most susceptible to the neurological complications. Several groups in the highly affected Asia-Pacific region are working towards vaccines against EV71 and some candidates have progressed to late-stage clinical trials with two vaccines recently reported to have been approved by the regulatory authorities in China. This report summarizes current issues and progress in the development of vaccines against EV71.

Matched MeSH terms: Clinical Trials as Topic
The comparison between the different generations of autologous chondrocyte implantation with other treatment modalities: a systematic review of clinical trials

Samsudin EZ, Kamarul T

Knee Surg Sports Traumatol Arthrosc, 2016 Dec;24(12):3912-3926.
PMID: 26003481

PURPOSE: This paper aims to review the current evidence for autologous chondrocyte implantation (ACI) generations relative to other treatment modalities, different cell delivery methods and different cell source application.
METHODS: Literature search was performed to identify all level I and II studies reporting the clinical and structural outcome of any ACI generation in human knees using the following medical electronic databases: PubMed, EMBASE, Cochrane Library, CINAHL, SPORTDiscus and NICE healthcare database. The level of evidence, sample size calculation and risk of bias were determined for all included studies to enable quality assessment.
RESULTS: Twenty studies were included in the analysis, reporting on a total of 1094 patients. Of the 20 studies, 13 compared ACI with other treatment modalities, seven compared different ACI cell delivery methods, and one compared different cell source for implantation. Studies included were heterogeneous in baseline design, preventing meta-analysis. Data showed a trend towards similar outcomes when comparing ACI generations with other repair techniques and when comparing different cell delivery methods and cell source selection. Majority of the studies (80 %) were level II evidence, and overall the quality of studies can be rated as average to low, with the absence of power analysis in 65 % studies.
CONCLUSION: At present, there are insufficient data to conclude any superiority of ACI techniques. Considering its two-stage operation and cost, it may be appropriate to reserve ACI for patients with larger defects or those who have had inadequate response to other repair procedures until hard evidence enables specific clinical recommendations be made.
LEVEL OF EVIDENCE: II.

Matched MeSH terms: Clinical Trials as Topic
Fulltext Major pathophysiological correlations of rosacea: a complete clinical appraisal

Vemuri RC, Gundamaraju R, Sekaran SD, Manikam R

Int J Med Sci, 2015;12(5):387-96.
PMID: 26005373 DOI: 10.7150/ijms.10608

Rosacea is a characteristic cutaneous disorder with a diverse clinical manifestations ranging from facial vascular hyper-reactivity to sebaceous gland hyperplasia. Many theories on pathophysiology of rosacea were proposed over the past decade, however the pathogenicity is poorly understood.

Matched MeSH terms: Clinical Trials as Topic
Ethnicity and drug therapy for hypertension

Amudha K, Wong LP, Choy AM, Lang CC

Curr Pharm Des, 2003;9(21):1691-701.
PMID: 12871202

Physiological and pharmacological responses may be influenced by ethnicity as a result of genetic factors, environmental factors and/or their interaction. This review is divided into 2 parts. Firstly, there will be overview of ethnicity as a determinant of drug metabolism and response with reference to antihypertensive agents. The concept of ethnicity has been applied extensively to the study of hypertension especially in American blacks in whom the hypertension is more common and more aggressive. Thus, the second part of this review will then focus on examining the black-white differences in physiological responses to pharmacological challenge that may provide a link between these models and known ethnic differences in drug responses. We will discuss the hypertension studies that have examined the relative effectiveness of different classes of antihypertensive agents including several recent cardiovascular outcome trials that either have a high proportion of blacks or were conducted entirely in black subjects.

Matched MeSH terms: Clinical Trials as Topic
AIDS vaccine research in Asia: needs and opportunities. Report from a UNAIDS/WHO/NIID meeting Tokyo, 28-30 October 1998

AIDS, 1999 Jul 30;13(11):UNAIDS 1-UNAIDS 13.
PMID: 10449273

A meeting was organized by the Joint United Nations Programme on HIV/AIDS (UNAIDS), the World Health Organisation (WHO) and the Japanese National Institute of Infectious Diseases (NIID) with the following objectives: (i) to discuss public health and economic rationale to accelerate the development and evaluation of HIV vaccines suitable for use in Asia; (ii) to review ongoing preclinical HIV vaccine research in Asia; (iii) to review the Asian experience in conducting clinical trials of HIV candidate vaccines; (iv) to explore possibilities for international collaboration between countries in the region and with other countries and institutions; and (v) to discuss issues related to availability of future effective HIV vaccines. The meeting was attended by participants from Australia, China, France, Germany, India, Japan, Malaysia, Myanmar, South Korea, Thailand, United Kingdom, and the United States of America. The HIV epidemic in Asia is rapidly spreading and has already resulted in a total of 7 million HIV infections in the region. The epidemic already has a significant public health and economic impact, which may be worse in the future, unless effective intervention programmes are successfully implemented. A safe, effective, and affordable vaccine should be considered as the best hope for a long-term solution to the HIV epidemic in Asia. Asian scientists and institutions have established a number of international collaborations to isolate and characterize prevalent HIV-1 strains (mostly belonging to subtypes C and E) and are developing candidate vaccines based on these subtypes. In the region, phase I/II clinical trials of preventative HIV candidate vaccines have been conducted in Australia, China and Thailand. Since 1993, a comprehensive National AIDS Vaccine Plan has allowed Thailand to conduct phase I/II trials of six different preventative or therapeutic candidate vaccines, and the first phase III preventative efficacy trial has been approved. The meeting identified both the needs and the opportunities to intensify international collaboration to accelerate the development of HIV vaccines in Asia.

Matched MeSH terms: Clinical Trials as Topic
Fulltext Steroid therapy in obstructive airway diseases

Zainudin BMZ

Respirology, 1997 Mar;2(1):17-31.
PMID: 9424402 DOI: 10.1111/j.1440-1843.1997.tb00051.x

Asthma and chronic obstructive pulmonary disease (COPD) are two common illnesses that cause significant morbidity and mortality. Steroids are widely used in both conditions. They act through steroid or glucocorticoid receptors (GR) causing up or down regulation of protein synthesis resulting in an increase in lipocortin 1 and beta 2 adrenergic receptors, and decreased levels and activities of cytokines or cytokine receptors, which reduces the inflammatory process in the airways and decreases bronchial hyperreactivity. Consequently symptoms of airway obstruction are alleviated and lung function is improved. In asthma, steroids have been convincingly shown to be effective in the treatment of both acute exacerbations and chronic condition. In COPD, however, only a subset of patients seem to respond favourably to steroid therapy. Therapeutic trials are therefore recommended before committing to a long-term treatment in order to determine this subset of patients, as no markers of steroid responsiveness can be identified. The inhaled steroids currently available have a good safety profile with significant side effects occurring only occasionally. Such side effects are usually confined to the oropharynx, causing local irritation, candidiasis and dysphonia, which can be easily overcome. Biochemical abnormalities involving bone, adrenal, carbohydrate and lipid profiles have been noted with high doses of inhaled steroids; however, these have no significant clinical effects.

Matched MeSH terms: Clinical Trials as Topic
A double-blind comparison of nomifensine and amitriptyline in the treatment of depression

Ong SB, Lee CT

Acta Psychiatr Scand, 1981 Mar;63(3):198-207.
PMID: 7015790

A double-blind study was carried out to compare the efficacy and tolerability of nomifensine and amitriptyline in 17 Malaysian patients with moderate to severe depression. The two drugs did not differ with regard to antidepressant effect but nomifensine-treated subjects report fewer side-effects with no complaints of palpitations. Nomifensine also increases capacity for work and activity.

Matched MeSH terms: Clinical Trials as Topic
Fulltext Medicinal Plants with Anti-Leukemic Effects: A Review

Maher T, Ahmad Raus R, Daddiouaissa D, Ahmad F, Adzhar NS, Latif ES, et al.

Molecules, 2021 May 07;26(9).
PMID: 34066963 DOI: 10.3390/molecules26092741

Leukemia is a leukocyte cancer that is characterized by anarchic growth of immature immune cells in the bone marrow, blood and spleen. There are many forms of leukemia, and the best course of therapy and the chance of a patient's survival depend on the type of leukemic disease. Different forms of drugs have been used to treat leukemia. Due to the adverse effects associated with such therapies and drug resistance, the search for safer and more effective drugs remains one of the most challenging areas of research. Thus, new therapeutic approaches are important to improving outcomes. Almost half of the drugs utilized nowadays in treating cancer are from natural products and their derivatives. Medicinal plants have proven to be an effective natural source of anti-leukemic drugs. The cytotoxicity and the mechanisms underlying the toxicity of these plants to leukemic cells and their isolated compounds were investigated. Effort has been made throughout this comprehensive review to highlight the recent developments and milestones achieved in leukemia therapies using plant-derived compounds and the crude extracts from various medicinal plants. Furthermore, the mechanisms of action of these plants are discussed.

Matched MeSH terms: Clinical Trials as Topic
Fulltext Anti-Influenza with Green Tea Catechins: A Systematic Review and Meta-Analysis

Rawangkan A, Kengkla K, Kanchanasurakit S, Duangjai A, Saokaew S

Molecules, 2021 Jun 30;26(13).
PMID: 34209247 DOI: 10.3390/molecules26134014

Influenza is one of the most serious respiratory viral infections worldwide. Although several studies have reported that green tea catechins (GTCs) might prevent influenza virus infection, this remains controversial. We performed a systematic review and meta-analysis of eight studies with 5,048 participants that examined the effect of GTC administration on influenza prevention. In a random-effects meta-analysis of five RCTs, 884 participants treated with GTCs showed statistically significant effects on the prevention of influenza infection compared to the control group (risk ratio (RR) 0.67, 95%CIs 0.51-0.89, P = 0.005) without evidence of heterogeneity (I2= 0%, P = 0.629). Similarly, in three cohort studies with 2,223 participants treated with GTCs, there were also statistically significant effects (RR 0.52, 95%CIs 0.35-0.77, P = 0.001) with very low evidence of heterogeneity (I2 = 3%, P = 0.358). Additionally, the overall effect in the subgroup analysis of gargling and orally ingested items (taking capsules and drinking) showed a pooled RR of 0.62 (95% CIs 0.49-0.77, P = 0.003) without heterogeneity (I2= 0%, P = 0.554). There were no obvious publication biases (Egger's test (P = 0.138) and Begg's test (P = 0.103)). Our analysis suggests that green tea consumption is effective in the prophylaxis of influenza infections. To confirm the findings before implementation, longitudinal clinical trials with specific doses of green tea consumption are warranted.

Matched MeSH terms: Clinical Trials as Topic
Repurposing Pentoxifylline for the Treatment of Fibrosis: An Overview

Wen WX, Lee SY, Siang R, Koh RY

Adv Ther, 2017 06;34(6):1245-1269.
PMID: 28484954 DOI: 10.1007/s12325-017-0547-2

Fibrosis is a potentially debilitating disease with high morbidity rates. It is estimated that half of all deaths that occur in the USA are attributed to fibrotic disorders. Fibrotic disorders are characterized primarily by disruption in the extracellular matrix deposition and breakdown equilibrium, leading to the accumulation of excessive amounts of extracellular matrix. Given the potentially high prevalence of fibrosis and the paucity of agents currently available for the treatment of this disease, there is an urgent need for the identification of drugs that can be utilized to treat the disease. Pentoxifylline is a methylxanthine derivative that is currently approved for the treatment of vascular diseases, in particular, claudication. Pentoxifylline has three main properties: improving the rheological properties of blood, anti-inflammatory, and antioxidative. Recently, the effectiveness of pentoxifylline in the treatment of fibrosis via attenuating and reversing fibrotic lesions has been demonstrated in several clinical trials and animal studies. As a result of the limited availability of antifibrotic agents in the long-term treatment of fibrosis that can attenuate and even reverse fibrotic lesions effectively, it would be of particular importance to consider the potential clinical utility of pentoxifylline in the treatment of fibrosis. Thus, this paper discusses the evolving roles of pentoxifylline in the treatment of different types of fibrosis.

Matched MeSH terms: Clinical Trials as Topic
Cimetidine for chronic duodenal ulceration: short term clinical trial

Chelvam P, Zhmad Z

Med J Malaysia, 1979 Mar;33(3):274-6.
PMID: 392272
Matched MeSH terms: Clinical Trials as Topic
Fulltext Chemotherapeutic trials in leprosy. 6. Pilot study of the riminophenazine derivative B.663 in low dosage (100 mgm. twice weekly) in the treatment of lepromatous leprosy

Waters MFR

Int. J. Lepr. Other Mycobact. Dis., 1968;36(4):391-9.
PMID: 4898403

Using a trial design previously evolved at Sungei Buloh Leprosarium, a pilot trial was performed of B.663, in the dosage of 100 mgm. twice weekly, in eight patients with previously untreated lepromatous leprosy. The therapeutic results, as measured by clinical, bacteriologic and histologic assessment, and especially by the rate of fall of the morphologic index, were similar to those obtained with sulfone therapy or with 0.663 in the dosage of 300 mgm. daily. Although B.663 pigmentation was produced in all eight patients, it developed more slowly and was less intense than with standard dosage. Difficulties resulting from skin discoloration in assessing the clinical progress of patients on B.663 are discussed.

Matched MeSH terms: Clinical Trials as Topic
Controlled clinical trial of "Atromid" (androsterone with ethyl-p-chlorophenoxy-isobutyrate) and "Persantin" (dipyridamole) in cases of myocardial infarction

Teik KO, Poh FW, Fun CS, Mong BC

Med J Malaya, 1966 Mar;20(3):186-204.
PMID: 4223070
Matched MeSH terms: Clinical Trials as Topic
Non-regulatory related factors leading to off-label prescribing in children: A concept map

Balan S, Hassali MA, Mak VSL

Res Social Adm Pharm, 2017 Nov;13(6):1219-1221.
PMID: 28576615 DOI: 10.1016/j.sapharm.2017.05.013
Matched MeSH terms: Clinical Trials as Topic
Fulltext Gene therapy and type 1 diabetes mellitus

Chellappan DK, Sivam NS, Teoh KX, Leong WP, Fui TZ, Chooi K, et al.

Biomed Pharmacother, 2018 Dec;108:1188-1200.
PMID: 30372820 DOI: 10.1016/j.biopha.2018.09.138

BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by T cell-mediated self-destruction of insulin-secreting islet β cells. Management of T1DM is challenging and complicated especially with conventional medications. Gene therapy has emerged as one of the potential therapeutic alternatives to treat T1DM. This review primarily focuses on the current status and the future perspectives of gene therapy in the management of T1DM. A vast number of the studies which are reported on gene therapy for the management of T1DM are done in animal models and in preclinical studies. In addition, the safety of such therapies is yet to be established in humans. Currently, there are several gene level interventions that are being investigated, notably, overexpression of genes and proteins needed against T1DM, transplantation of cells that express the genes against T1DM, stem-cells mediated gene therapy, genetic vaccination, immunological precursor cell-mediated gene therapy and vectors.
METHODS: We searched the current literature through searchable online databases, journals and other library sources using relevant keywords and search parameters. Only relevant publications in English, between the years 2000 and 2018, with evidences and proper citations, were considered. The publications were then analyzed and segregated into several subtopics based on common words and content. A total of 126 studies were found suitable for this review.
FINDINGS: Generally, the pros and cons of each of the gene-based therapies have been discussed based on the results collected from the literature. However, there are certain interventions that require further detailed studies to ensure their effectiveness. We have also highlighted the future direction and perspectives in gene therapy, which, researchers could benefit from.

Matched MeSH terms: Clinical Trials as Topic

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