Advances In Drug Therapy Research Articles

Pharmacological Activity of Plant Extracts in Self-Nanoemulsifying Drug Delivery System Dosage Form: Narrative Review

The utilization of medicinal plants as therapeutic agents has obstacles to achieving the target action due to their low solubility. Self-Nanoemulsifying Drug Delivery System (SNEDDS) is a method developed to increase the solubility of poorly water-soluble substances, such as medicinal plant extracts. This review aims to present a narrative overview of the potential utilization of SNEDDS in enhancing the pharmacological activity of plant extracts. Article searches were conducted on several websites, such as Google Scholar, PubMed, and ScienceDirect. Literature studies showed that the use of SNEDDS formulations in several medicinal plants such as dayak onion, soursop leaf, papaya leaf, bay leaf, kale, sidaguri, black cumin, mangosteen peel, harendong, pineapple peel, and cocoa is more effective than the administration of extracts alone because it can increase the solubility and bioavailability of a compound. Pharmacologically, SNEDDS shows its success in enhancing antioxidant, anti-inflammatory, analgesic, antidiabetic, antihyperglycemic, antimalarial, immunostimulant, antimicrobial, anticancer, wound healing, and hepatoprotective activities in various plant extracts. The utilization of SNEDDS formulations in plant-based drugs has a positive impact on the advancement of drug therapy, especially for compounds that have low solubility.

Advances in Drug Therapy for Metastatic Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a notably poor prognosis. A large number of patients with PDAC develop metastases before they are diagnosed with metastatic pancreatic cancer (mPDAC). For mPDAC, FOLFIRINOX or gemcitabine plus nab-paclitaxel are the current first-line treatments. It is important to note, however, that many patients will fail chemotherapy because of drug resistance. ​Heterogeneous tumors and complex tumor microenvironments are key factors. As a result, clinical researchers are exploring a variety of alternative treatment modalities. Current understanding of the molecular signature and immune landscape of PDAC has motivated the emergence of different targeted and immune-based therapeutic approaches, some of which have shown promising results. The purpose of this review is to discuss the new targets and new drugs for mPDAC in terms of specific pathogenic factors such as metabolic vulnerability, DNA damage repair system, tumor microenvironment and immune system, in order to identify potential vulnerabilities in mPDAC patients and hopefully improve the prognosis of mPDAC patients.

Recent advances in drug therapy for tuberculosis

Despite global efforts to control and eradicate tuberculosis (TB), it remains a significant source of morbidity and mortality worldwide. Drug-resistant TB (DRTB) is a significant public health threat with implications for global health security, economic burden, and access to quality care. To address this challenge, continued investment in research, surveillance, and innovative strategies is crucial. Collaboration among international organizations, governments, and health-care systems is crucial to tackle this global health concern effectively. Bedaquiline (BDQ), a diarylquinoline drug, is indicated for combination therapy in adult patients with pulmonary multidrug-resistant TB (MDRTB). The Food and Drug Administration (FDA) granted accelerated approval in December 2012, based on analysis of time to sputum culture conversion from two phase 2 trials. The World Health Organization (WHO) published interim policy guidance for BDQ in conjunction with WHO-recommended MDRTB treatments in June 2013. The European Medicines Agency authorized Delamanid as a first-in-class bicyclic nitroimidazole for treating MDRTB, which has been used in 89 and 54 nations due to its quick acquisition of resistance. To prevent resistance, combined therapy with additional anti-TB drugs is advised, along with proper use and drug resistance monitoring. Pretomanid received approval from the US FDA in August 2019 after a phase III trial yielded encouraging results. The bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) regimen, a component of the BPaLM regimen, has been approved for treating adults with extensive pulmonary DRTB or treatment-intolerant or non-responsive MDRTB. This significant advancement in management offers improved clinical outcomes and quality of life for MDRTB patients. The inclusion in the WHO guidelines is encouraging for global combat against DRTB. Researchers have identified and investigated new drug targets within the TB pathogenesis, offering promising avenues for the development of innovative anti-TB drugs. Advances in pediatric TB treatment have made significant progress, focusing on improved diagnostic methods, effective drug treatments, and global initiatives. Nanotechnology has shown promising potential in various fields, including medicine and TB treatment.

10167-MET-8 CLINICAL CHARACTERISTICS AND TREATMENT STRATEGY OF CANCER CASES PRESENTING WITH CENTRAL NERVOUS SYSTEM SYMPTOMS

Abstract Metastatic brain tumors were previously reported with prognoses of approximately 6 months. The accuracy of diagnostic imaging and advances in drug therapy have improved the treatment outcomes of various types of cancer. On the other hand, patients with advanced cancer who are detected with neurological symptoms caused by metastatic brain tumors usually face difficulty in deciding on a treatment strategy. In this study, we reported the results of cancer patients who were first detected with central nervous system symptoms in the last 10 years and treated at our hospital.There were 14 patients treated at our hospital from 2013 to 2022 with CNS symptoms as the initial symptom. The mean age was 65.5 years, and the most common primary cancer was lung cancer in 11 cases (9 NSCLC and 2 SCLC). The OS examined in the 11 lung cancer cases was 14 months. Among NSCLC, only 2 cases had EGFR mutation and no cases had ALK fusion gene. The mean Lung-molGPA was 0.89 in 9 patients with NSCLC and 0.75 in 2 patients with SCLC, and the expected survival time was 6.9 months and 2.8 months.With advances in drug therapy, median survival for patients with NSCLC brain metastases has been reported to range from 7 months to 2 years for patients with EGFR mutations and 4 years for patients with ALK fusion gene. Thus, it is necessary to consider treatment strategies according to primary tumor, histology, and genetic information, rather than considering metastatic brain tumors as a single entity.The results of this study suggest that aggressive therapeutic intervention may prolong the survival period expected at the time of initial diagnosis, even in cancer patients who are found to have metastatic brain tumors.

Chronic Hepatitis B Infection: Current and Emerging Therapeutic Strategies.

The chronic infection of the hepatitis B virus (CHB) represents a major public health problem worldwide. Despite the availability of an effective prophylactic vaccine, millions of hepatitis B patients are at increased risk of developing chronic liver disease. The currently available treatments for HBV infection include interferon and nucleos(t)ide analogues that are effective at suppressing viral load and preventing or delaying the progression of liver disease. However, these treatments offer somewhat unsatisfactory clinical cures due to the persistence of the intrahepatic pool of covalently closed circular DNA (cccDNA) that serves as a reservoir for viral progenies and a potential source of recurring infections. Elimination of viral cccDNA remains a challenge for scientists and pharmaceutical industries in order to achieve the eradication and control of HBV infection. This would involve a detailed understanding of the molecular mechanisms of cccDNA formation, its intracellular stability, and regulation during replication and transcription. Recent advances in drug therapy have heralded a new horizon of novel therapeutic approaches for CHB infection, with several promising antiviral and immunomodulatory agents currently in preclinical or clinical testing. However, approval of any new curative therapy would involve rigorous evaluation of the efficacy and safety of each treatment and defining correct endpoints associated with improved clinical outcomes. This article summarizes the current landscape of HBV treatments, and drugs in clinical trials and highlights the most recent anti-HBV small molecules designed to directly target HBV or to improve immune response during chronic infection.

A review of Lapatinib, a tyrosine kinase inhibitor, in HER2+ metastatic breast cancer treatment development

Metastatic breast cancer continues to have high mortality rates despite the numerous advances in drug therapy. Breast cancer patients have acquired resistance to current treatments, and severe adverse effects, such as cardiotoxicity caused by Trastuzumab, further contribute to the high mortality rate. Therefore, novel drugs with greater specificity and less severe adverse effects must be developed to combat the rise in treatment resistance. Lapatinib, a tyrosine kinase inhibitor, is an attractive drug of choice since lapatinib is not associated with cardiotoxicity, given its greater specificity to HER2 receptors compared to trastuzumab. This review provides a brief overview of tyrosine kinase inhibitors and their overall mechanism of action in treating HER2+ cancers. The study further summarizes the mechanism of action of Lapatinib, its pharmacokinetic properties, its clinical applications, the tools of the act of lapatinib resistance, and recent advances in developing derivatives of Lapatinib to combat lapatinib-acquired resistance.

Research advances in drug therapy of endometriosis.

Endometriosis is one of the most common benign gynecological disorders in reproductive-aged women. The major symptoms are chronic pelvic pain and infertility. Despite its profound impact on women's health and quality of life, its pathogenesis has not been fully elucidated, it cannot be cured and the long-term use of drugs yields severe side effects and hinders fertility. This review aims to present the advances in pathogenesis and the newly reported lead compounds and drugs managing endometriosis. This paper investigated Genetic changes, estrogen-dependent inflammation induction, progesterone resistance, imbalance in proliferation and apoptosis, angiogenesis, lymphangiogenesis and neurogenesis, and tissue remodeling in its pathogenesis; and explored the pharmacological mechanisms, constitutive relationships, and application prospects of each compound in the text. To date, Resveratrol, Bay1316957, and bardoxifene were effective against lesions and pain in controlled animal studies. In clinical trials, Quinagolide showed no statistical difference with the placebo group; the results of phase II clinical trial of the IL-33 antibody have not been announced yet; clinical trial stage III of vilaprisan was suspended due to drug toxicity. Elagolix was approved for the treatment of endometriosis-related pain, but clinical studies of Elagolix for the pretreatment of patients with endometriosis to before In vitro fertilization treatment have not been fulfilled. The results of a clinical study of Linzagolix in patients with moderate to severe endometriosis-related pain have not been disclosed yet. Letrozole improved the fertility of patients with mild endometriosis. For endometriosis patients with infertility, oral GnRH antagonists and aromatase inhibitors are promising drugs, especially Elagolix and Letrozole.

Pomegranate polyphenol punicalagin improves learning memory deficits, redox homeostasis, and neuroinflammation in aging mice.

Alzheimer's disease (AD) is an irreversible, progressive brain disorder characterized by loss of memory and cognitive dysfunction in the aged. Despite remarkable advances in drug therapy, effective pharmacological interventions are rare. Punicalagin (PU) is an active antioxidant polyphenol found in pomegranates, raspberries, blueberries, and chestnuts that has attracted considerable attention owing to its strong antioxidant and anti-inflammatory properties. The current study focused on the neuroprotective effect of PU on aging mice and its potential mechanisms. In this study, we first evaluated the protective effect of PU on neuro-2a (N2a) cell damage mediated by BV2 microglia-induced neuroinflammation. The in vivo D-galactose (D-gal)-induced brain aging model demonstrated that PU ameliorated deficits in learning and memory and prevented neuroinflammation, which was evident from the decrease in microglial activation and astrocytosis. Furthermore, PU reduced the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) and inhibited NLRP3 inflammasome activation, reducing the levels of inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), interleukin-18 (IL-18), and interleukin-1 beta (IL-1β) in both accelerated aging and naturally senescent mouse models. PU effectively improved neuroinflammation, learning and memory deficits, and redox homeostasis in aging mice, and it could be a potential therapeutic agent for AD.

Management of Multiple Myeloma: A Review for General Practitioners in Oncology

Multiple myeloma (MM) is a malignant clonal plasma cell disorder in the bone marrow and is the second-most common hematologic malignancy in adults. Although patients with MM have a moderate life expectancy, it remains a heterogeneous disease that often requires multiple lines of chemotherapy for durable control and long-term survival. This review outlines current management strategies for both transplant-eligible and transplant-ineligible patients as well as for relapsed and refractory disease. Advances in drug therapies have widened management options and improved survival. In this paper, we also discuss implications for special populations and survivorship care.

PAIN MANAGEMENT IN LUNG CANCERS : EXPERIENCE OF THE MEDICAL ONCOLOGY DEPARTMENT OF HASSAN II HOSPIATL IN FEZ

Despite advances in drug therapy, pain management for patients with lung cancer remains complex. Lung cancer is known to be one of the most painful cancers. Objective: In this study we evaluate the management of pain in patients treated for lung cancer, all stages combined, in the oncology department of the Hassan II University Hospital of Fez. Mean : cross-sectional study of 71 patients collected over a period of one year using a questionnaire specifying the characteristics of the pain, its etiology, the stage of the disease, the analgesic treatments prescribed and the relief obtained by the treatment. Results: The mean age of the patients was 63.5 years with extremes ranging from 48 to 85 years. Male gender was predominant (68%), 67% of patients had metastatic cancer: 42% had bone metastases. Nociceptive pain was assessed by the visual analog scale (VAS) and neuropathic pain by the DN4 Questionnaire. Severe pain, characterized by a VAS score higher than 7, or of moderate intensity with impact on sleep and daily activity, was reported in 60.5% of our patients, mostly young subjects, all with advanced cancer. The pain was acute in 5% of cases, subacute in 32% of patients and chronic in 63% of cases. Neuropathic pain was found in 23% of patients. The pain was controlled by analgesics, level II, in association with an anti-inflammatory agent or antidepressants in 37.3%. 62.7% of patients required morphine. An average daily dose of 60mg of morphine was required to relieve pain, 15 patients reported paroxysmal pain attacks of strong intensity requiring the prescription of sublingual Fentanyl. The use of analgesic radiotherapy in combination with morphine was noted in 10 patients (9.8%). However, a small percentage (2.8%) of patients were resistant to the above-mentioned analgesics, requiring the use of non-drug techniques to relieve them. Conclusion: Our survey confirms the persistent problem of inadequate management of cancer pain. An interesting approach is to improve.

Research advances in drug therapy for abdominal aortic aneurysms over the past five years: An updated narrative review

BackgroundAbdominal aortic aneurysms (AAA) rupture can lead to patient death. Surgical treatment is currently the optimal treatment for AAA with large diameter (≥50 mm). For AAA with small diameter (30–50 mm), how to administer effective pharmacological treatment to reduce aneurysm expansion rate and rupture risk is the current focus in the field of vascular surgery. There is still no effective drug for the treatment of asymptomatic AAA. MethodsThis article searches the PubMed, Web of Science, Embase, and Cochrane databases for clinical studies on the drug treatment of abdominal aortic aneurysms in the past 5 years. The latest progress in the drug treatment of AAA was reviewed, including antibiotics, antihypertensive drugs, antiplatelet drugs, hypoglycemic drugs, hypolipidemic drugs, mast cell inhibitors and corticosteroids. Results25 studies were included in this narrative review. Among them, metformin revealed therapeutic effect in 2 prospective cohort study and 3 retrospective cohort study. The therapeutic effect of statins was controversial in 3 retrospective cohort study. However, the definite therapeutic effects of antihypertensive agents, antibiotics, mast cell inhibitors, antiplatelet agents and corticosteroids on abdominal aortic aneurysms have not been verified in prospective studies. ConclusionMetformin provided a positive effect in reducing expansion rate, rupture risk, and perioperative mortality. The therapeutic effect of statins was controversial, which warrant further validation in prospective cohorts. However, there is still a lack of effective agents for the treatment of AAA based on recent studies.

Pharmacological Management of Pulmonary Tuberculosis: A Century of Expert Opinions in Cecil Textbook of Medicine.

Advances in drug therapy for pulmonary tuberculosis have had an extraordinary impact on the incidence of tuberculosis in the United States in the past century, which has decreased from 113/100,000 persons in 1920 to 2.2/100,000 in 2020. Modern treatments have contributed to a remarkable decrease in hospitalizations and mortality and have had a significant impact on the duration and severity of illness, quality of life, and work potential of affected persons. What are the milestones of the changes in the expert approach to the pharmacological management of pulmonary tuberculosis in the past century? To determine the changes in the experts' approach to the management of pulmonary tuberculosis, as presented in a widely used textbook in the United States. The chapters describing the management of pulmonary tuberculosis in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. In the preantibiotic era (1927-1943), the Cecil authors emphasized rest, good food, and fresh air as the treatment pillars for pulmonary tuberculosis. The modern era (1947-1971) recorded the discovery of all the drugs that are still used for the initial treatment, in the following order: streptomycin, para-aminosalicylic acid, isoniazid, pyrazinamide, ethambutol, cycloserine, kanamycin, ethionamide, capreomycin, and rifampin. In the postmodern era (1975-2020), therapeutic advances continued with trials of many drug combinations aimed at ameliorating the duration of treatment, drug resistance adverse effects, and poor the recent addition of fluoroquinolones, bedaquiline, and clofazimine. The pharmacological management of tuberculosis has remained archaic until the middle of the 20th century. Fundamental progress occurred in a very short period (1947-1971) and was because of the recognition of the antituberculous effect of many antibiotics and chemotherapy agents. The challenges created by mycobacterial infections resistant to multiple drugs remain and have prompted the addition of new drugs in the past decade.

Pharmacological Management of Inflammatory Bowel Disease: a Century of Expert Opinions in Cecil Textbook of Medicine.

Advances in drug therapy for inflammatory bowel disease (IBD) [Crohn disease and ulcerative colitis (UC)] have contributed to a decrease in the severity of these chronic and disabling conditions. What are the milestones of the changes in the expert approach to the pharmacological management of IBD in the past century? To determine the changes in the experts' approach to the management of regional ileitis and UC, as presented in a widely used textbook in the United States. The chapters presenting the management of IBD in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. No specific interventions existed from 1927 through 1942. The pharmacological management of IBD has had 3 slightly overlapping eras starting in 1943. During the first period (1943-1951), the medical management relied on antibiotics, primarily sulfonamides and chloramphenicol. In the second (1955-75), experts recommended the use of adrenocorticotropic hormone or corticosteroids and 5-aminosalicylate. In the third era, which commenced in 1979 and is continuing to date, the pharmacological interventions have been expanded and refined to include 5 main drug classes, 5-aminosalicylates (sulfasalazine, mesalamine, and olsalazine), corticosteroids (prednisone and budesonide), immunomodulators (azathioprine, 6-mercaptopurine, cyclosporine, and tofacitinib), biologics (infliximab adalimumab certolizumab pegol, and natalizumab), and antibiotics (metronidazole and ciprofloxacin). A consensus exists that the monoclonal antibodies again tumor necrosis factor alpha are cost-effective for induction and maintenance of clinical remission in both UC (golimumab) and Crohn disease (certolizumab pegol). The newer agents ustekinumab (a monoclonal antibody to the interleukin p40 subunit) and vedolizumab (a monoclonal antibody to the homing receptor integrin complex) have also performed well. The pharmacological management of IBD has been the focus of intense research and development in the past 60 years. The pillars of drug treatment have been 5-aminosalicylates and corticosteroids. Recent pharmacological innovations (immunomodulators and biologicals) constitute an encouraging paradigm shift in the treatment of UC and Crohn disease.

Potential Strategies for Kidney Regeneration With Stem Cells: An Overview.

Kidney diseases are a major health problem worldwide. Despite advances in drug therapies, they are only capable of slowing the progression of kidney diseases. Accordingly, potential kidney regeneration strategies with stem cells have begun to be explored. There are two different directions for regenerative strategies, de novo whole kidney fabrication with stem cells, and stem cell therapy. De novo whole kidney strategies include: 1) decellularized scaffold technology, 2) 3D bioprinting based on engineering technology, 3) kidney organoid fabrication, 4) blastocyst complementation with chimeric technology, and 5) the organogenic niche method. Meanwhile, stem cell therapy strategies include 1) injection of stem cells, including mesenchymal stem cells, nephron progenitor cells, adult kidney stem cells and multi-lineage differentiating stress enduring cells, and 2) injection of protective factors secreted from these stem cells, including growth factors, chemokines, and extracellular vesicles containing microRNAs, mRNAs and proteins. Over the past few decades, there have been remarkable step-by-step developments in these strategies. Here, we review the current advances in the potential strategies for kidney regeneration using stem cells, along with their challenges for possible clinical use in the future.

Pharmacological Management of Primary Arterial Hypertension: A Century of Expert Opinions in Cecil Textbook of Medicine.

Advances in drug therapy for primary (or essential) arterial hypertension have contributed to a significant decrease in the frequency and severity of strokes, coronary artery disease and heart failure, and chronic renal insufficiency. What are the milestones of the changes in the expert approach to the pharmacological management of arterial hypertension in the past century? To determine the changes in the experts' approach to the management of arterial hypertension, as presented in a widely used textbook in the United States. The chapters presenting the management of arterial hypertension in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. The pharmacological management of arterial hypertension has had 3 overlapping eras in the timeframe subject to our investigation. In the empiric era (1927-1947), experts were recommending nonspecific interventions for sedation. The premodern era (1955-1963) relied on ganglion blockers, sympathetic blockers, and direct vasodilators. The modern era (1967-2020), which includes drugs used in current clinical practice, saw the introduction of diuretics (1967), beta-blockers (1971), alpha-blockers (1982), calcium channel blockers (1985), angiotensin-converting enzyme inhibitors (1985), angiotensin receptor blockers (2000), and direct renin inhibitors (2008). The pharmacological management of arterial hypertension has been the focus of intense and successful research and development in the second half of the 20th century.

Safety and efficacy of salvage surgery for non-small cell lung cancer: a retrospective study of 46 patients from four Keio-affiliated hospitals.

Advances in drug therapy and radiotherapy for non-small cell lung cancer resulted in an increased number of salvage surgeries for initially unresectable tumors. This study aimed to evaluate the safety and efficacy of salvage surgery for non-small cell lung cancer. We defined salvage surgery as (1) surgery for local recurrence/residual tumor after definitive chemoradiotherapy/radiotherapy (salvage surgery in a narrow sense) or (2) conversion surgery after non-surgical treatment. We retrospectively analyzed patients who underwent salvage surgery at four Keio University-affiliated hospitals. Forty-six patients were included. The initial clinical stage was I in 4 patients (9%), III in 19 (41%), and IV in 23 (48%). Initial treatment before salvage surgery was chemoradiotherapy in 10 patients (24%), radiotherapy in 4 (9%), and drug therapy in 32 (67%). Pneumonectomy, lobectomy, segmentectomy, and wedge resection were performed in 2 (4%), 37 (80%), 3 (7%), and 4 (9%) patients, respectively. Complete resection was achieved in 41 patients (89%). Postoperative complications occurred in 11 patients (24%). Initial chemoradiotherapy/radiotherapy was an independent predictor of postoperative complications (odds ratio 10, p = 0.03). The 30- and 90-day mortality rates were 0 and 2%, respectively. The 5-year overall and progression-free survival rates were 66 and 30%, respectively. The safety and efficacy of salvage surgery for non-small cell lung cancer were acceptable. Salvage surgery was a viable treatment option for selected patients with recurrent/residual tumors after non-surgical treatments.

Ursolic Acid Increases Strength in mdx Mice Model and may Decrease Fibrosis Deposition by TGF-ß Downregulation

Dystrophin disfunction results in sarcolemma destabilization, leading muscle cell damage by continuous degeneration cycles and limited regeneration. In muscle dystrophy, caused by dystrophin dysfunction, inflammation, necrosis and fibrosis are pathophysiological muscle function loss characteristics. As a genetic disease, this muscle dystrophy has no cure, however, advances in drug therapy using glucocorticoids can decrease the disease progression. Subsequently, alternative therapies were studied, such as ursolic acid (UA), that inhibits muscle atrophy and increases muscle mass and strength. Herein, we used 10 mg/kg daily supplementation in mdx mice for 4 weeks to evaluate serum creatine phosphokinase (CPK), muscle strength (Kondziela test), muscular organization (histology) and expression of fibrosis related genes (TGF-ß, TNF-α, mstn and ostn). UA supplementation increased muscle morphological organization, motor strength and decreased muscular TGF-ß expression. Altogether, the gene expression profile, histological organization and strength could suggest that UA treatment did not stop the fibrogenesis but decreased its progress.

Drug Combinations: A New Strategy to Extend Drug Repurposing and Epithelial-Mesenchymal Transition in Breast and Colon Cancer Cells.

Despite the progressive research and recent advances in drug therapy to treat solid tumours, the number of cases and deaths in patients with cancer is still a major health problem. Drug repurposing coupled to drug combination strategies has been gaining interest among the scientific community. Recently, our group proposed novel drug combinations for breast and colon cancer using repurposed drugs from different classes (antimalarial and central nervous system (CNS)) and chemotherapeutic agents such as 5-fluorouracil (5-FU), paclitaxel (PTX), and found promising results. Here, we proposed a novel drug combination using different CNS drugs and doxorubicin (DOX), an antineoplastic used in breast cancer therapy, and studied their anticancer potential in MCF-7 breast cancer cells. Cells were treated with each drug alone and combined with increasing concentrations of DOX and cell viability was evaluated by MTT and SRB assays. Studies were also complemented with morphological evaluation. Assessment of drug interaction was performed using the CompuSyn and SynergyFinder software. We also compiled our previously studied drug pairs and selected the most promising ones for evaluation of the expression of EMT biomarkers (E-cadherin, P-cadherin, vimentin, and β-catenin) by immunohistochemistry (IHC) to assess if these drug combinations affect the expression of these proteins and eventually revert EMT. These results demonstrate that combination of DOX plus fluoxetine, benztropine, and thioridazine at their IC50 can improve the anticancer effect of DOX but to a lesser degree than when combined with PTX (previous results), resulting in most of the drug interactions being antagonist or additive. This suggests that the choice of the antineoplastic drug influences the success of the drug combination. Collectively, these results also allow us to conclude that antimalarial drugs as repurposed drugs have enhanced effects in MCF-7 breast cancer cells, while combination with CNS drugs seems to be more effective in HT-29 colon cancer cells. The IHC results demonstrate that combination treatments increase E-cadherin expression while reducing P-cadherin, vimentin, and β-catenin, suggesting that these treatments could induce EMT reversal. Taken together, these results could provide promising approaches to the design of novel drug combinations to treat breast and colon cancer patients.

Pharmacological Management of Atrial Fibrillation: A Century of Expert Opinions in Cecil Textbook of Medicine.

Advances in drug therapy for atrial fibrillation (AF) have had a significant impact on the quality of life of a substantial majority of affected persons, which has contributed to a remarkable decrease in the frequency and severity of thromboembolic complications, hospitalizations, and mortality. What are the milestones of the changes in the expert approach to the pharmacological management of AF in the past century? To determine the changes in the experts' approach to the management of AF, as presented in a widely used textbook in the United States. The chapters presenting the management of AF in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. AF was consistently described in Cecil Textbook of Medicine as the most common sustained arrhythmia in adults. The authors emphasized its thromboembolic complications and potential for hemodynamic deterioration. Rate control with digitalis and rhythm control with quinidine were the standard in 1927. The pharmacological advances have focused on atrioventricular nodal blocking for rate control, conversion to and maintenance of sinus rhythm, and preventive anticoagulation. The first new class of drugs for rate control was beta-adrenergic receptor blockers, starting with propranolol which was introduced in 1979, followed by the calcium channel blocker verapamil in 1988. Rhythm control with amiodarone, a potassium channel blocker, has been recommended since 2004, and the sodium channel blockers propafenone and flecainide became part of standard therapy in 2008. Anticoagulation with warfarin was recommended starting in 2000, followed by the introduction of direct thrombin inhibitor in 2012 and factor Xa inhibitors in 2016. The pharmacological management of AF was unchanged for more than 50 years (1927-1979), a period during which the devastating effects of thromboembolic complications were not addressed. The major therapeutic advance is represented by preventive anticoagulation with the newer, safer, and more user-friendly direct thrombin and factor Xa inhibitors.

Review of the diagnosis and treatment of brain metastases.

Brain metastases (BM) occur in at least 10% of cancer patients, and are one of the main causes of cancer-related deaths and significant deterioration in the quality of life of cancer patients due to the neurological deterioration caused by brain compression and tumor invasion. Whole-brain irradiation has been emphasized as the standard treatment for BM. However, recent clinical trials including the JLGK0901 and JCOG0504 trials conducted in Japan have established therapeutic evidence for the use of stereotactic radiosurgery with regular follow-up with magnetic resonance imaging for BM. In addition to surgery and stereotactic radiotherapy, advances in drug therapy for BM, such as tyrosine kinase inhibitors and immune checkpoint inhibitors, are expected. This review describes the history and the recent evidence of the diagnosis and treatment of BM.