Recent advances in the pharmacological treatment of colorectal cancer

Recent advances in the treatment of colorectal cancer have lead to significant gains in response rates and survival. The combination of newer agents such as irinotecan and oxaliplatin with 5-fluorouracil/leucovorin using various dosing schedules in the metastatic setting has resulted in a steady improvement in the outcome of patients with colorectal cancer. Experimental therapies such as epidermal growth factor receptor inhibitors, vascular endothelial growth factor inhibitors and cyclooxygenase-2 inhibitors, have shown promise in early clinical trials and have acceptable toxicity profiles. Efforts towards improving risk-stratification of stage II colorectal cancer patients and optimising therapy in patients with advanced disease, have focused on molecular and genetic markers. It is hoped that the addition of new therapies to existing drug combinations, as well as further advances in the understanding of colorectal cancer biology, will lead to further improvement in survival and quality of life for patients.     

Recent advances in the pharmacological treatment of tinnitus

Tinnitus is an extremely prevalent condition that impinges on the lives of sufferers to varying degrees. In some people, it is a fairly minor irritation but, for many, the tinnitus intrudes to such a degree that it affects their ability to lead a normal life, and in some very extreme cases has resulted in suicide. Insomnia, inability to concentrate and depression are commonly reported to accompany the condition. Relief can be reliably obtained using intravenous lignocaine, which indicates that pharmacology can provide a route for effective alleviation of the condition. In this article, Julie Simpson and Ewart Davies review the potential pharmacological therapies, and emphasize that clinical research has been hampered by the absence of a reliable objective assessment of the tinnitus and by the variable nature of the complaint.     

Recent advances in the treatment of gastric cancer

Gastric cancer is one of the most common cancers in the world. The prognosis of the disease is poor, with only 40% of patients eligible to undergo potentially curative surgery. Even for those patients who undergo a complete resection, the rate of recurrence is very high. Extensive studies of multidisciplinary adjuvant treatment have been conducted seeking to improve the cure rates in the past two decades. The benefit of D2 dissection is still controversial and is undergoing prospective evaluation. Preliminary results from the United States Gastrointestinal Intergroup study, a well designed trial, have shown overall survival benefit of postoperative chemoradiation therapy. Neoadjuvant chemotherapy or chemoradiation is under active study in order to increase the number of patients to undergo potential curative surgery. Although many chemotherapy regimens have been developed recently, only modest clinical efficacy has been demonstrated for advanced metastatic disease. So far, there is no single regimen considered to be standard.     

Recent advances in the pharmacological management of pain

Pain is an unpleasant sensation that originates from ongoing or impending tissue damage. Management of different types of pain (acute, postoperative, inflammatory, neuropathic or cancer) is the most frequent issue encountered by clinicians and pharmacological therapy is the first line of approach for the treatment of pain. This review presents and discusses recent clinical advances regarding both the improvements in delivery of analgesic drugs and improvements in the design of analgesic molecules. The new modalities of administration of analgesics used in the clinic are reviewed, including skin patches, oral and mucosal sprays, transdermal delivery systems and intranasal administration. New insights are then presented on standard drugs used to relieve pain, such as opioids (including tramadol), NSAIDs including selective cyclo-oxygenase-2 inhibitors, paracetamol (acetaminophen), local anaesthetics and adjuvant analgesics such as antidepressants, anticonvulsants (gabapentin and pregabalin), cannabinoids, ketamine and others (e.g. nefopam). Although the understanding of pain mechanisms has improved significantly recently, much more is yet to be discovered and awaited. Broadening of our knowledge is needed to improve basic and clinical research in this field in order to better alleviate pain in millions of people.     

Recent advances in the treatment of epithelial ovarian cancer

Ovarian cancer leads to more fatalities than any other form of gynaecological cancer in North America and Europe. Over the last 30 years survival figures have improved somewhat due to improvements in diagnosis, surgery and chemotherapy. Despite these advances, the majority of patients will die from their disease, with the overall 5-year survival being just 30%. The majority of patients with this disease will require treatment with cytotoxic chemotherapy. It is now well established that the platinum agents (cisplatin or carboplatin) are the most important drugs to be included in first-line regimens. More recently, randomised trials have confirmed the benefit of the addition of taxanes to platinum-containing regimens and the standard of care has become the combination of carboplatin and paclitaxel. Several unanswered questions remain regarding the optimal schedule, the optimum duration of treatment, possible benefits to be gained from the addition of other drugs and whether paclitaxel the best taxane. Despite high response rates to first line chemotherapy, the majority of patients with advanced ovarian cancer will relapse and will be candidates for further chemotherapy, which can palliate symptoms and improve survival even in recurrent disease. For a patient relapsing within six months of first-line treatment, studies have shown that there is little point in rechallenge with the same drugs. However, for patients who have a longer treatment-free interval the response rates to rechallenge with platinum is significant. A number of drugs have been shown to have activity in platinum- and taxane-refractory disease and are approved for this and/or other applications. These include topotecan, etoposide, pegylated liposomal doxorubicin, epirubicin, gemcitabine, altretamine, oxaliplatin and vinorelbine. Anti-oestrogens such as tamoxifen have a small but significant response rate. Recurrent ovarian cancer is a good setting to test investigational agents and compounds with promising activity including new platinums and taxoids, as well as a range of new compounds. Non-cytotoxic approaches that are showing promise include therapies designed to overcome drug resistance, signal transduction inhibitors, immunotherapy and gene therapy.     

Recent developments in the pharmacological treatment of advanced pancreatic cancer

Metastatic pancreatic cancer is one of the leading causes of cancer-related death in North America and Europe. The high mortality rate associated with pancreatic cancer is related to the fact that the vast majority of patients develop incurable, metastatic disease. Such patients have, in the past, had few treatment options. In recent years, however, the systemic administration of gemcitabine has been accepted as a standard first-line treatment for patients with advanced pancreatic cancer. While treatment with gemcitabine has been shown to result in both clinical benefit and in prolongation of survival, objective tumour responses following therapy with gemcitabine are relatively uncommon and median survival times remain short. Current efforts have, therefore, focused on evaluating chemotherapy regimens in which gemcitabine is combined with a second cytotoxic agent. Several such combinations appear to be associated with higher objective response rates than single-agent gemcitabine and have been well-tolerated in early clinical trials. Ongoing, prospectively randomised clinical trials will help better define the efficacy of these new combinations and will determine if they result in a significant benefit when compared to gemcitabine monotherapy. A number of novel chemotherapeutic and biological agents also appear promising and are likely to play a future role in the treatment of patients with advanced pancreatic cancer.     

Recent developments in the pharmacological treatment of advanced pancreatic cancer

Metastatic pancreatic cancer is one of the leading causes of cancer-related death in North America and Europe. The high mortality rate associated with pancreatic cancer is related to the fact that the vast majority of patients develop incurable, metastatic disease. Such patients have, in the past, had few treatment options. In recent years, however, the systemic administration of gemcitabine has been accepted as a standard first-line treatment for patients with advanced pancreatic cancer. While treatment with gemcitabine has been shown to result in both clinical benefit and in prolongation of survival, objective tumour responses following therapy with gemcitabine are relatively uncommon and median survival times remain short. Current efforts have, therefore, focused on evaluating chemotherapy regimens in which gemcitabine is combined with a second cytotoxic agent. Several such combinations appear to be associated with higher objective response rates than single-agent gemcitabine and have been well-tolerated in early clinical trials. Ongoing, prospectively randomised clinical trials will help better define the efficacy of these new combinations and will determine if they result in a significant benefit when compared to gemcitabine monotherapy. A number of novel chemotherapeutic and biological agents also appear promising and are likely to play a future role in the treatment of patients with advanced pancreatic cancer.     

Recent pharmacological advances in the treatment of preterm membrane rupture,labour and delivery

Preterm delivery (before 37 completed weeks of gestation) is the major determinant of infant mortality. In women with a previous preterm birth associated with bacterial vaginosis, prophylactic antibiotics (e.g., metronidazole) reduce the risk of preterm birth and low birth weight. Trichomonas vaginalis increases the risk of preterm delivery, but metronidazole is not beneficial for this and may even be detrimental. Antibiotic use (e.g., erythromycin) prolongs pregnancy in late premature rupture and has health benefits for the neonate. However, antibiotics are probably not useful in preterm labour. Intramuscular 17α-progesterone and vaginal progesterone reduce the rate of preterm labour in high-risk pregnancies, including previous spontaneous preterm delivery. Magnesium sulfate, β₂-adrenoceptor agonists and the oxytocin-receptor antagonist, atosiban, are effective in reducing uterine contractions short-term, but there is little evidence that this leads to improved outcomes for the neonate. However, tocolysis with calcium-channel blockers does seem to lead to better outcomes for the neonate. Fetal side effects, such as ductus arteriosus constriction and impaired renal function, are associated with the inhibition of prostaglandin synthesis with indomethacin. New approaches and more effective drugs are required in the treatment of preterm delivery.     

Recent pharmacological advances in the treatment of preterm membrane rupture, labour and delivery

Preterm delivery (before 37 completed weeks of gestation) is the major determinant of infant mortality. In women with a previous preterm birth associated with bacterial vaginosis, prophylactic antibiotics (e.g., metronidazole) reduce the risk of preterm birth and low birth weight. Trichomonas vaginalis increases the risk of preterm delivery, but metronidazole is not beneficial for this and may even be detrimental. Antibiotic use (e.g., erythromycin) prolongs pregnancy in late premature rupture and has health benefits for the neonate. However, antibiotics are probably not useful in preterm labour. Intramuscular 17alpha-progesterone and vaginal progesterone reduce the rate of preterm labour in high-risk pregnancies, including previous spontaneous preterm delivery. Magnesium sulfate, beta2-adrenoceptor agonists and the oxytocin-receptor antagonist, atosiban, are effective in reducing uterine contractions short-term, but there is little evidence that this leads to improved outcomes for the neonate. However, tocolysis with calcium-channel blockers does seem to lead to better outcomes for the neonate. Fetal side effects, such as ductus arteriosus constriction and impaired renal function, are associated with the inhibition of prostaglandin synthesis with indomethacin. New approaches and more effective drugs are required in the treatment of preterm delivery.     

Recent advances in biomarkers for cancer diagnosis and treatment

With the availability of new technologies and the increased interest of medical practitioners to use molecular biomarkers in early detection and diagnosis, and in the prediction of therapeutic treatment efficacy and clinical outcomes, the academic and research institutions, as well as the pharmaceutical industry, have increased their efforts to develop novel molecular biomarkers for several human diseases, including cancer. The identification of molecular biomarkers also enables the development of a new generation of diagnostic products and to integrate diagnostics and therapeutics. This integrated approach will aid in 'individualizing' the medical practice. Here, we address issues related to the development of biomarkers, novel technological platforms used for drug development, future technologies and strategies for validating biomarkers for their clinical utility.     

白藜芦醇的抗肿瘤药理作用研究新进展

白藜芦醇(3,4',5,-三羟基二苯乙烯;resveratro1)是一种活性非黄酮多酚物质,广泛存在于葡萄、花生、虎杖等天然食物或药物中,一般认为其是一种植物抗毒素,在植物受到病原性进攻和环境恶化时产生的.     

Recent advances in occupational cancer

The contribution of occupational and environmental exposures to the etiology of cancer is a topic of considerable scientific and public interest. If an occupational environmental exposure is associated with cancer in man, then both the exposure and the disease are preventable by appropriate protection. In order to enhance the awareness and timeliness of new information concerning occupational cancer, the University of California, San Francisco, School of Medicine in conjunction with the Northern California Occupational Health Center and the National Institutes of Occupational Safety and Health, the American Cancer Society sponsored a two day meeting in San Francisco at the end of 1983. Five of the presentations are highlighted in this review. In addition, twenty special questions of clinical relevance concerning occupational and environmental cancers are reviewed with the consensus answers given.     

Recent advances in cancer research

The 95th annual meeting of the American Association for Cancer Research was held on March 27-31, 2004, in Orlando, Florida, United States. All aspects of cancer research, from drug discovery, new targets, cellular and in vivo models, clinical trials, and prevention were presented and discussed. A selection from the many excellent presentations and posters are described with an emphasis on new compounds, new methods to identify cancers, and recent discoveries that may change how we treat cancer.     

Recent advances in the treatment of hyponatremia

Hyponatremia is a common and potentially serious electrolyte disorder, most often caused by excessive arginine vasopressin (AVP) secretion. Conventional management of hyponatremia is based on graded steps starting from water restriction in mild cases to administration of saline in symptomatic cases, which may not be effective. A major new approach in the treatment of hyponatremia is the development of AVP receptor antagonists that directly inhibit the effect of increased AVP which results in the excretion of electrolyte free water. This review summarizes pathophysiology, conventional treatment and future directions in the treatment of hyponatremia.     

Recent advances in the treatment of hyponatremia

Hyponatremia is a common and potentially serious electrolyte disorder, most often caused by excessive arginine vasopressin (AVP) secretion. Conventional management of hyponatremia is based on graded steps starting from water restriction in mild cases to administration of saline in symptomatic cases, which may not be effective. A major new approach in the treatment of hyponatremia is the development of AVP receptor antagonists that directly inhibit the effect of increased AVP which results in the excretion of electrolyte free water. This review summarizes pathophysiology, conventional treatment and future directions in the treatment of hyponatremia.     

Recent advances in drug delivery strategies for treatment of ovarian cancer

Introduction: Ovarian cancer is associated with the highest mortality rate of all gynecological malignancies, due in part to inadequate treatment strategies and the asymptomatic nature of the disease. Current standard of care includes surgery and systemic chemotherapy. However, this approach can result in toxicities and eventual disease relapse, due to the emergence of multidrug resistance. Drug delivery systems (DDS) have shown promise in overcoming many of the limitations facing conventional treatment regimens.

Areas covered: This review provides an overview of recent advances in DDS strategies for the treatment ovarian cancers. Nano-sized systems, including nanoparticles, micelles, liposomes and drug conjugates; microspheres; implants and injectable depots are discussed. The advantages, limitations and clinical potential of these strategies are also outlined.

Expert opinion: Nano-sized DDS enable passive targeting to tumors due to their size, and further improvements in tumor localization can be made using targeting moieties. Microspheres, implants and injectable depots have been investigated for peritoneal localized and sustained therapy. Overall, the benefits of using DDS for ovarian cancer therapy include higher drug levels at the diseased site, circumvention of drug resistance mechanisms, minimization of non-specific toxicities, improvements in solubility of poorly soluble drugs and elimination of toxicities associated with conventionally used pharmaceutical excipients.     

Recent advances in drug delivery strategies for treatment of ovarian cancer

INTRODUCTION: Ovarian cancer is associated with the highest mortality rate of all gynecological malignancies, due in part to inadequate treatment strategies and the asymptomatic nature of the disease. Current standard of care includes surgery and systemic chemotherapy. However, this approach can result in toxicities and eventual disease relapse, due to the emergence of multidrug resistance. Drug delivery systems (DDS) have shown promise in overcoming many of the limitations facing conventional treatment regimens. AREAS COVERED: This review provides an overview of recent advances in DDS strategies for the treatment ovarian cancers. Nano-sized systems, including nanoparticles, micelles, liposomes and drug conjugates; microspheres; implants and injectable depots are discussed. The advantages, limitations and clinical potential of these strategies are also outlined. EXPERT OPINION: Nano-sized DDS enable passive targeting to tumors due to their size, and further improvements in tumor localization can be made using targeting moieties. Microspheres, implants and injectable depots have been investigated for peritoneal localized and sustained therapy. Overall, the benefits of using DDS for ovarian cancer therapy include higher drug levels at the diseased site, circumvention of drug resistance mechanisms, minimization of non-specific toxicities, improvements in solubility of poorly soluble drugs and elimination of toxicities associated with conventionally used pharmaceutical excipients.