Deletion of Slc6a14 reduces cancer growth and metastatic spread and improves survival in KPC mouse model of spontaneous pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is lethal. There is a dire need for better therapeutic targets. Cancer cells have increased demand for sugars, amino acids, and lipids and therefore up-regulate various nutrient transporters to meet this demand.

α-Methyl-l-tryptophan as a weight-loss agent in multiple models of obesity in mice.

α-Methyl-L-tryptophan (α-MLT) is currently in use as a tracer in its 11C-labeled form to monitor the health of serotonergic neurons in humans. In the present study, we found this compound to function as an effective weight-loss agent at pharmacological doses in multiple models of obesity in mice. The drug was able to reduce the body weight when given orally in drinking water (1 mg/ml) in three different models of obesity: normal mice on high-fat diet, Slc6a14-null mice on high-fat diet, and ob/ob mice on normal diet.

SLC6A14 deficiency is linked to obesity, fatty liver, and metabolic syndrome but only under conditions of a high-fat diet.

SLC6A14 is a Na/Cl-coupled transporter for neutral/cationic amino acids, expressed in ileum and colon. A single-nucleotide polymorphism (SNP), rs2011162 (-22,510C > G), in SLC6A14 coding for the 3'-untranslated region (3'-UTR) is associated with obesity in humans. But the impact of this polymorphism on the transporter expression and its connection to obesity are not known.

Hereditary hemochromatosis promotes colitis and colon cancer and causes bacterial dysbiosis in mice.

Hereditary hemochromatosis (HH), an iron-overload disease, is a prevalent genetic disorder. As excess iron causes a multitude of metabolic disturbances, we postulated that iron overload in HH disrupts colonic homeostasis and colon-microbiome interaction and exacerbates the development and progression of colonic inflammation and colon cancer. To test this hypothesis, we examined the progression and severity of colitis and colon cancer in a mouse model of HH (Hfe-/-), and evaluated the potential contributing factors.

Yellow-Gold Polarized Light Microscopy May Improve Accuracy of Pathological Staging of Colorectal Adenocarcinoma.

Introduction Polarized light (PL) has been used in pathology for multiple reasons, including the demonstration of foreign bodies, the evaluation of crystals, and the demonstration of fibrosis. We incidentally found that yellow-gold polarization routinely occurs surrounding desmoplastic scar tissue abutting the invasive glands of colonic adenocarcinoma. We hypothesized that evaluating the use of polarized light over a series of invasive adenocarcinomas of the large intestine might produce evidence of its utility.

Chronic exposure to excess iron promotes EMT and cancer via p53 loss in pancreatic cancer.

Based on the evidence that hemochromatosis, an iron-overload disease, drives hepatocellular carcinoma, we hypothesized that chronic exposure to excess iron, either due to genetic or environmental causes, predisposes an individual to cancer. Using pancreatic cancer as our primary focus, we employed cell culture studies to interrogate the connection between excess iron and cancer, and combined and studies to explore the connection further. Ferric ammonium citrate was used as an exogenous iron source.

Operative Management of T1b Gallbladder Carcinoma with Concurrent Hepatic Anastomosing Hemangioma.

We report a case of stage T1b gallbladder carcinoma with concurrent hepatic anastomosing hemangioma managed by operative resection. We review the work-up and surgical management of this patient. We also discuss the relevant literature of both gallbladder cancer and hepatic anastomosing hemangioma, a recently described and rare variant of capillary hemangioma.

Isolated Asymptomatic Metastatic Melanoma to the Colon: A Case Report.

Metastatic melanoma is generally rare, and the colon is a very rare metastatic site. We report a case of asymptomatic, isolated metastatic melanoma to the colon. Asymptomatic patients are usually not expected to have metastatic lesions in the colon.

DFseq: Distribution-Free Method to Detect Differential Gene Expression for RNA-Sequencing Data.

Many current RNA-sequencing data analysis methods compare expressions one gene at a time, taking little consideration of the correlations among genes. In this study, we propose a method to convert such an one-dimensional comparison approach into a two-dimensional evaluation of the ratio of standard deviations (SD) of two constructed random variables. This method allows the identification of differentially expressed genes while controlling a preset significance level conditional on the read count mean-variance relationship.

Novel Treatment of Melanoma: Combined Parasite-Derived Peptide GK-1 and Anti-Programmed Death Ligand 1 Therapy.

Recent successes in the development of new therapies for metastatic melanoma, such as mitogen-activated protein kinase pathway inhibitors, anticytotoxic T lymphocyte-associated antigen-4, and programmed cell death protein 1/programmed cell death ligand 1 (PD-L1) pathway-blocking antibodies, as well as combination strategies, all yielded promising results, changing the continually evolving landscape of therapeutic options for patients with melanoma. One promising new treatment modality is based on the use of immunomodulatory monoclonal antibodies that enhance the function of components of the antitumor immune response such as T cells or block immunologic checkpoints that restrain effective antitumor immunity. Program death-1 receptor and its ligand, PD-L1, is a major mechanism by which a tumor suppresses T cell-mediated antitumor immune responses.

Rare Occurrence of a Poorly Differentiated Neuroendocrine Tumor of the Bladder.

Neuroendocrine tumors rarely occur in the urinary bladder. They can be carcinomatous, subdivided into small cell and large cell pathology. Small cell carcinoma of the bladder is a rarity that may present at an advanced pathologic stage.

The Peridural Membrane of the Human Spine is Well Innervated.

There is evidence that low back pain may originate from a peridural membrane (PDM) at the inferior and medial aspect of neural foramen of the lumbar spine. The objective of this investigation was to determine if this membrane contains neural elements suggestive of sensory innervation with nociceptive function. Spines of four embalmed and three non-embalmed human cadavers were dissected using a sagittal approach to the neural foramen.

Hormone Replacement Therapy, Likely Neither Angel Nor Demon.

Purpose: A decline in breast cancer incidence has been attributed to the reduction in hormone replacement therapy (HRT) prescriptions since the publication of the landmark WHIT paper in 2003. Concurrently, a relationship between HRT and cerebrovascular disease incidence has also been suggested. No generalized analysis of HRT prescription rates and breast cancer incidence rates that included more than seven years of data.

Countries with high circumcision prevalence have lower prostate cancer mortality.

The present study determined the relationship of male circumcision (MC) prevalence with prostatic carcinoma mortality rate in the 85 countries globally for which data on each were available. MC prevalence in different countries were obtained from a WHO report and allocated to WHO categories of 81%-100%, 20%-80%, and 0%-19%. Prostatic carcinoma mortality data were from Globoscan, gross national income per capita as well as male life expectancy were from a World Bank report, and percentages of Jews and Muslims by country were from the Pew Research Institute and the North American Jewish Data Bank.

Implications on clinical management of the small renal mass in patients 80 years of age and older based on a retrospective review of the SEER database.

Purpose: Incidental detection of small renal masses has increased in recent years with increased use of various imaging modalities, and a substantial number of diagnoses are made in the elderly population. Minimally invasive surgical procedures have previously been established as options with excellent long-term oncological results, but surveillance strategies have more recently been introduced as alternatives for surgical intervention. This study reviews the outcomes for elderly patients treated with observation or surgery for small renal masses in order to better elucidate optimal management strategies.

Treatment of Hepatic Epithelioid Hemangioendothelioma: Finding Uses for Thalidomide in a New Era of Medicine.

Hepatic epithelioid hemangioendothelioma (HEH) is extremely rare, occurring in 1 to 2 per 100,000, with chemotherapy options not well defined. Our case involved a 49-year-old female who had hepatic masses and metastasis to the lungs with a liver biopsy revealing HEH. After developing a rash from sorafenib, thalidomide was started with the progression of disease stabilized.

Osteoclastic giant cell tumor of the pancreas.

Introduction: Pancreatic giant cell tumors are rare, with an incidence of less than 1% of all pancreatic tumors. Osteoclastic giant cell tumor (OGCT) of the pancreas is one of the three types of PGCT, which are now classified as undifferentiated carcinoma with osteoclast-like giant cells.

Presentation Of Case: The patient is a 57 year old woman who presented with a 3 week history of epigastric pain and a palpable abdominal mass.

Odds of death after glioblastoma diagnosis in the United States by chemotherapeutic era.

Bevacizumab (BZM) and temozolomide (TMZ) have been shown to be beneficial in the treatment of patients with glioblastoma. We sought evidence for the benefit of BZM in the general patient population at large. The Surveillance, Epidemiology, and End Results SEER database was queried for patients diagnosed with glioblastoma between 2000 and 2009, divided into a pre-TMZ era (January 2000-June 2003), a transitional era (July 2003-March 2005), a TMZ era (April 2005-October 2007), and a BZM-TMZ era (November 2007-December 2009).

Outcomes for patients who are diagnosed with breast and endometrial cancer.

The present study sought to determine the survival outcomes for women diagnosed with breast and endometrial cancer. Using SEER data, a population-based cohort study of women diagnosed with breast and endometrial cancer was conducted. Kaplan-Meier survival curves were created for disease-specific survival rates.

PSA screening and deaths from prostate cancer after diagnosis--a population based analysis.

Background: The United States Preventative Health Task Force recently recommended prostate specific antigen (PSA) screening be abandoned, believing the results of prior studies failed to show benefits that outweighed risks. Prior analyses did not include a complete 10 year follow-up in their analyses.

Methods: SEER rate sessions were used to obtain for U.

Sonographic and clinical features of upper extremity deep venous thrombosis in critical care patients.

Background-Aim. Upper extremity deep vein thrombosis (UEDVT) is an increasingly recognized problem in the critically ill. We sought to identify the prevalence of and risk factors for UEDVT, and to characterize sonographically detected thrombi in the critical care setting.

Sonographic lobe localization of alveolar-interstitial syndrome in the critically ill.

Introduction. Fast and accurate diagnosis of alveolar-interstitial syndrome is of major importance in the critically ill. We evaluated the utility of lung ultrasound (US) in detecting and localizing alveolar-interstitial syndrome in respective pulmonary lobes as compared to computed tomography scans (CT).

Evaluation of an intraoperative algorithm based on near-infrared refracted spectroscopy monitoring, in the intraoperative decision for shunt placement, in patients undergoing carotid endarterectomy.

Background: We evaluated whether the use of an intraoperative algorithm based on cerebral oximetry with near-infrared refracted spectroscopy (NIRS) monitoring, could aid in the intraoperative decision for shunt placement, in patients undergoing carotid endarterectomy (CEA).

Methods: In this prospective, randomized, controlled study were included 253 patients who underwent CEA under general anesthesia. They were randomly allocated in Group A (n=83) using NIRS monitoring and the suggested algorithm, Group B (n=84) using NIRS monitoring without the algorithm and Group C (n=86) who served as controls.