Hepatocellular Carcinoma: Molecular Mechanisms and Targeted Therapies.

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumors worldwide. HCC is a complex process that is associated with several etiological factors, which in turn result in aberrant activation of different cellular and molecular pathways and the disruption of balance between activation and inactivation of protooncogenes and tumor suppressor genes, respectively. Since HCC most often occurs in the setting of a diseased or cirrhotic liver and most of the patients are diagnosed at the late stage of disease, prognosis is generally poor. At present, limited treatment options with marginal clinical benefits are available. Systemic therapy, particularly in the form of conventional cytotoxic drugs, are generally ineffective. In recent years, molecular-targeted therapies have been clinically used to treat various cancers, including liver cancer. This approach inhibits the growth of tumor cells by interfering with molecules that are involved in carcinogenesis, which makes it more selective and specific than cytotoxic chemotherapy. Many clinical trials have been carried out while using molecular targeted drugs in advanced HCC with many more in progress. The clinical trials in HCC to date have evaluated a single-targeted therapy alone, or two or more targeted therapies in parallel. The aim of this review is to provide insight of various molecular mechanisms, leading to HCC development and progression, and also the range of experimental therapeutics for patients with advanced HCC. The review will summarize different clinical trials data the successes and failures of these treatments, as well as the most effective and approved drugs designed against HCC.

Novel easily separable core-shell Fe3O4/PVP/ZIF-8 nanostructure adsorbent: optimization of phosphorus removal from Fosfomycin pharmaceutical wastewater.

A new easily separable core-shell Fe3O4/PVP/ZIF-8 nanostructure adsorbent was synthesized and then examined for removal of Fosfomycin antibiotic from synthetic pharmaceutical wastewater. The removal process of Fosfomycin was expressed through testing the total phosphorus (TP). A response surface model (RSM) for Fosfomycin adsorption (as mg-P L-1) was used by carrying out the experiments using a central composite design. The adsorption model showed that Fosfomycin adsorption is directly proportional to core-shell Fe3O4/PVP/ZIF-8 nanostructure adsorbent dosage and time, and indirectly to initial Fosfomycin concentration. The removal increased by decreasing the pH to 2. The Fosfomycin removal was done at room temperature under an orbital agitation speed of 250 rpm. The adsorption capacity of core-shell Fe3O4/PVP/ZIF-8 nanostructure adsorbent reached around 1200 mg-P g-1, which is significantly higher than other MOF adsorbents reported in the literature. The maximum Langmuir adsorption capacity of the adsorbent for Fosfomycin was 126.58 mg g-1 and Fosfomycin adsorption behavior followed the Freundlich isotherm (R 2 = 0.9505) in the present study. The kinetics was best fitted by the pseudo-second-order model (R 2 = 0.9764). The RSM model was used for the adsorption process in different target modes.

Metastatic Small Cell Carcinoma Presenting as Acute Pancreatitis.

Small cell carcinoma is a malignant lung cancer with poor prognosis that occurs almost exclusively in heavy smokers. Small cell cancer typically arises from the central airways, with the most common presentation being a large hilar mass with bulky mediastinal adenopathy. Small cell lung cancer rarely metastasizes to pancreatic tissue and presents as acute pancreatitis. Here, we describe a case of metastatic small cell lung carcinoma initially presenting as acute pancreatitis. The patient underwent CT of the abdomen, magnetic resonance cholangiopancreatography, and endoscopic ultrasound with biopsy which confirmed the diagnosis of small cell lung carcinoma. After positron emission tomography staging, the patient was subsequently treated with radiotherapy in tandem with multiple cycles of cisplatin and etoposide with positive treatment response.

Optimization of a saturated gas plant: Meticulous simulation-based optimization - A case study.

An optimization-simulation strategy has been applied by coupling a commercial process simulator (Aspen HYSYS®) with a programming tool (MATLAB®) to produce a precise steady state simulation-based optimization of a whole green-field saturated gas plant as a real case study. The plant has more than 100-components and comprises interacting three-phase fractionation towers, pumps, compressors and exchangers. The literature predominantly uses this coupling to optimize individual units at small scales, while paying more attention to optimizing discrete design decisions. However, bridging the gap to scalable continuous design variables is indispensable for industry. The strategy adopted is a merge between sensitivity analysis and constrained bounding of the variables along with stochastic optimization algorithms from MATLAB® such as genetic algorithm (GA) and particle swarm optimization (PSO) techniques. The benefits and shortcomings of each optimization technique have been investigated in terms of defined inputs, performance, and finally the elapsed time for such highly complex case study. Although, both GA and PSO were satisfactory for the optimization, the GA provided greater confidence in optimization with wider ranges of constrained bounds. The implemented strategy precisely reached the best operating conditions, within the range covered, by minimizing the total annual cost while maintaining at least 92% butane recovery as a process guarantee for the whole plant. The optimization-simulation strategy applied in the current work is recommended to be used in brownfields to optimize the operating conditions since they are susceptible to continuous changes in feedstock conditions.

A Rare Case of Cannabis-induced Acute Pancreatitis.

Acute pancreatitis is a sudden inflammatory condition of the pancreas, caused mainly by gallstones and alcohol abuse. A significant proportion of acute pancreatitis cases remain idiopathic. Recent reports have highlighted cannabis use as an etiology of acute pancreatitis. A few case reports are available that report the association of cannabis with acute pancreatitis. Considering the global use of cannabis medically and illicitly, it becomes imperative to explore this adverse effect of cannabis use especially in idiopathic cases of acute pancreatitis. Here, in this report, we present a case of acute pancreatitis with no obvious cause. The patient was a 48-year-old female with no history of alcohol use. She had a history of cholecystectomy with normal serum triglycerides and calcium levels. The patient was consuming marijuana (cannabis) daily for the last three years. The diagnosis of cannabis-induced acute pancreatitis was made in the patient after other causes were excluded. It is difficult to distinguish cannabis-induced pancreatitis as there are no clear and specific associated clinical features. The diagnosis of cannabis-induced pancreatitis becomes even more challenging due to the use of multiple drugs. It becomes difficult to point out the causative agent among the multitude of drugs. Hence, a detailed history of drug intake in cases of acute pancreatitis may help to identify the candidature of the drugs in the pathogenesis of the disease. In view of the increasing illicit and medical use of cannabis, it becomes quintessential for clinicians to consider pancreatitis as a possible adverse effect of cannabis.

Shortness of Breath: An Unusual Presentation of Bladder Injury. A Case Report and Literature Review of Urinothorax.

Urinothorax is the presence of urine in the pleural space. It can occur at any age and is more common in males. It typically results from obstructive uropathy but can also be caused by malignancy or trauma. Urinothorax is a rare cause of transudative pleural effusion and the only cause of low pH (pH <7.4) transudative effusion. We present the case of a 51-year-old female patient who had recently undergone a urological procedure and came to the emergency department reporting shortness of breath. A chest X-ray revealed a newly developed, large, right-sided pleural effusion. Thoracentesis yielded a transudative yellow fluid of normal pH with a creatinine-to-serum creatinine ratio of 1.7. A computed tomography (CT) cystogram showed extravasated contrast material within the pelvis, from which a diagnosis of urinothorax was confirmed and treated. Urinothorax is a rare diagnosis that requires a multidisciplinary treatment approach, usually including a pulmonologist and a urologist. After the genitourinary disease is treated, the urinothorax usually resolves.

Pancreaticopleural Fistula: A Rare Presentation and a Rare Complication.

Pancreaticopleural fistula (PPF) is a rare complication of pancreatitis that requires a high index of clinical suspicion as patients typically present with pulmonary symptoms related to the pleural effusion rather than pancreatitis. Diagnosis is made by detection of amylase in the pleural fluid. Magnetic resonance cholangiopancreatography can aid in visualizing the fistula. We present a case of massive left pleural effusion secondary to a PPF due to acute on chronic pancreatitis.

Cannabis Smoking-induced Diffuse Alveolar Hemorrhage.

Cannabis smoking is common among adolescents and young adults. Diffuse alveolar hemorrhage (DAH) is a rare and life-threatening complication of cannabis abuse. DAH is characterized by bleeding into alveoli secondary to the disruption of the alveolar-capillary basement membrane as a result of an injury at the level of alveolar microcirculation. The differential diagnosis of DAH includes systemic vasculitis, bland pulmonary hemorrhage, and alveolar damage. The impact of cannabis on the respiratory function includes mucus hypersecretion, inflammatory edema, and increased alveolar permeability. Moreover, in vitro coagulation studies on rats showed that two major cannabinoids, cannabinol and THC, have antithrombotic activity. We present two cases of cannabis use resulting in acute lung injury and diffuse alveolar hemorrhage.