ABSTRACT
Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.
ABSTRACT
ObjectiveTo report the treatment of the first imported Middle East respiratory syndrome (MERS) in China, and to investigate the clinical features and treatment of the patient.Methods On May 28th, 2015, the first patient of imported MERS to China was admitted to Department of Critical Care Medicine of Huizhou Municipal Central Hospital. The clinical features and treatments of this patient were analyzed.Results①A 43 years old male of South Korean nationality was admitted with the complaint of back ache for 7 days and fever 2 days with the following characteristics: back ache 7 days ago, without fever or cough or expectoration. He had been suspected to suffer from infection of Middle East respiratory syndrome coronavirus (MERS-CoV) by the Disease Control Department of South Korea, but no specific treatment was given. He had fever for 2 days with maximum body temperature of 39.7℃. He had no chills, cough, expectoration, short of breath, abdominal pain, diarrhea, frequent micturition, or urgency or pain of urination, and no sore throat. The patient had a history of exposure to MERS-CoV patient. He was considered to be a patient of the second batch of South Korean epidemic.② Auxiliary examination: 3 copies of throat swab specimens for virus nucleic acid detection were performed by the Disease Prevention Control Center of China (China CDC), and they were positive on May 29th, 2015, and also for serum, sputum and stool. Based on the results of whole genome sequence analysis, the virus strains were implicated to be derived from Riyahh and Jeddah regions of Saudi Arabia. On admission, the patient's blood test showed that the white blood cell count was low (3.22×109/L), the proportion of the neutrophils was high (0.73), and that of the platelet was low (81×109/L). On admission, the patient's chest X-ray showed that a small amount of infiltration in the lung.③ Treatment: a high-flow nasal cannula (HFNC) with oxygen concentration of 0.50-0.80 was given, with a flow rate was set at 60 L/min if tolerated. It was changed to a low flow oxygen inhalation nasal cannula on the 20th day, and oxygen treatment was stopped on the 24th day. Ribavirin 2.0 g was given as the first dose, and was switched to 600 mg every 8 h (q8h), and it was reduced to 600 mg q12h after 10 days, and extenuated since the 13th day. Ceftriaxone was added on the 4th day with 2.0 g a day , and it was changed to meropenem 2.0 g, q8h on the 7th day for 2 weeks. Gamma globulin was given for 7 days (20 g, qd). Thymosin-α1 was given on the 8th day for 2 weeks. Interferon was given once a week, but only one dose was used. At the same time symptomatic treatment such as methimazole and liver protection therapy were given.④ Patient began to cough at admission, and it disappeared on the 18th day. There was no sputum at first, then a small amount of sputum with a little blood appeared after the admission. Then there was cough without sputum. Mild shortness of breath and diarrhea after exertion were noticed. He had no chest pain, difficulty in breathing or other symptoms. There was dullness on percussion in both sides of chest, and it disappeared gradually. Fine moist rales were detectable in scapular area and interscapular area on the 5th day, and they disappeared after 3 days. Breath sounds on both sides was weak, and it became more obvious in the right lung after 5 days, and returned to normal after 18 days. He had a sustaining fever for 1 week with the maximum temperature of 39.5℃, then the body temperature returned to normal. The viral nucleic acid test as performed by the Center for Disease Control of Guangdong (CDC, Guangdong) showed that the pharyngeal swab cultured turned negative on the 3rd day, that of serum specimens turned negative on the 8th day, that of stool specimen after 2 weeks, and it was persistently positive for sputum culture until 5 days before discharge. The oxygenation index gradually increased, and it was over 300 mmHg (1 mmHg = 0.133 kPa) after 15 days. Pleural effusion was rapidly increased during the first week as shown by chest X-ray films, and it began to be absorbed gradually in the second week, but it was not completely absorbed until discharge.Conclusions The disease course of the reported patient was short, with an acute onset, with fever as the chief complaint, but there were no respiratory symptoms, though there were high fever, cough, shortness of breath, diarrhea and other clinical symptoms after admission. Virus in sputum disappeared after treatment, but pleural effusion was not completely absorbed. Negative test for virus in sputum was late, indicating that clearance of virus was slow from the lungs. It is the first case of MERS in China, therefore, the clinical manifestations and the treatment strategy need to be further explored.
ABSTRACT
Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is a novel coronavirus which can cause severe acute respiratory illness with a high mortality rate .There is no proven medication or vaccine for MERS-CoV .Currently MERS-CoV has spread from the main epidemic area ,the Middle East area ,to many other countries including United States of America and has the potential of global endemic .It has raised global public health concerns regarding the current situation and its future evolution .This review will mainly focus on the research progress of MERS-CoV about the animal reservoir and transmission , infection mechanisms and development of anti-viral drugs or vaccine .The goal is to provide with useful references to the devel-opment of specific drug and vaccine and an effective control and prevention of M ERS-CoV infection .
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Hepatitis is common disease in Bangladesh. As a country of the Asia Pacific region Bangladesh is considered to be a high risk country for developing hepatitis A and B. This study represents the pattern and types of treatment of hepatitis in two tertiary care hospitals in Bangladesh; Bangabandhu Sheikh Mujib Medical University and Dhaka Medical Collage Hospital. 140 patients were selected among whom 80 were male and 60 female. The patients were asked to fill up a questioner. Prescriptions of all the patients were reviewed and the duty doctors were consulted for further clarification of the cases. From the data obtained over a 3 month long survey it was found that hepatitis A, B and C are most common in this country. Most of the patients develop classical sign and symptoms of hepatitis; most commonly jaundice and weight loss. About 50% hepatitis cases contributed a viral cause. 42.86% patients undergo preventive treatment whereas 57.14% patients are treated with drugs. Lamivudine, Adefovir and Ribavirin were the commonly used drugs in viral hepatitis. The prevalence of different forms of hepatitis in Bangladesh is high. Bangladesh is at the high risk region of hepatitis A and B. Routine immunizations and community education regarding the diseases are highly warranted here
ABSTRACT
Background: Long term use of ganciclovir (GCV) is associated with acquired resistance to it. Ninety percent of the responsible mutations occur in cytomegalovirus (CMV) UL 97 gene. Aim: To search for these mutations, comparing nucleotide sequences of CMV-positive samples from post transplant and immunocompromised patients receiving GCV, with sequences of CMV isolates obtained from subjects not exposed to the drug. Patients and Methods: Codons 440 to 465 of gene UL 97, in-cluding the most common mutations causing resistance to GCV, were amplifed in 33 plasma samples from patients exposed to GCV and in 15 urine samples of newborns. Both populations and their nucleotide sequences were compared with the prototype strain CMV AD169. Results: Samples of exposed patients had multiple mutations but only one had a mutation associated with clinical resistance (M460I). Eight subjects had the D605E mutation, whose role in resistance is controversial. The remaining 150 mutations were silent mutations. Conclusions: A low frequency of mutations associated with CMV resistance to GCV was found in these exposed and unexposed samples. These mutations may refect coexistence of multiple genetic variants of CMV. The absence of clinical expression of resistance, even with these mutations, can be explained by the use of GCV for a shorter lapse than that associated with the appearance of resistance.