Pictilisib-Induced Resistance Is Mediated through FOXO1-Dependent Activation of Receptor Tyrosine Kinases in Mucinous Colorectal Adenocarcinoma Cells.

The phosphatidylinositol (PI3K)/AKT/mTOR axis represents an important therapeutic target to treat human cancers. A well-described downstream target of the PI3K pathway is the forkhead box O (FOXO) transcription factor family. FOXOs have been implicated in many cellular responses, including drug-induced resistance in cancer cells.

Cytoreduction with hyperthermic intra peritoneal and intra thoracic chemotherapy for metastatic Sertoli-Leydig cell tumor of the ovary.

Sertoli Leydig cell tumor (SLCT) is a rare sex-cord stromal tumor of the ovary that generally has a benign course. Here, we report an unusual case of recurrent, metastatic SLCT and its unique management with a combination of cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, hyperthermic intrathoracic chemotherapy, and systemic chemotherapy.

Bilateral blockade of MEK- and PI3K-mediated pathways downstream of mutant KRAS as a treatment approach for peritoneal mucinous malignancies.

Mucinous colorectal adenocarcinomas (MCAs) are clinically and morphologically distinct from nonmucinous colorectal cancers (CRCs), show a distinct spectrum of genetic alterations (higher KRAS mutations, lower p53, high MUC2), exhibit more aggressive behavior (more prone to peritoneal dissemination and lymph node involvement) and are associated with poorer response to chemotherapy with limited treatment options. Here, we report the effectiveness of combinatorial targeting of two KRAS-mediated parallel pathways in reducing MUC2 production and mucinous tumor growth in vitro and in vivo. By knockdown of mutant KRAS we show that, mutant KRAS (a) is necessary for MUC2 production in vitro and (b) synergistically engages PI3K/AKT and MEK/ERK pathways to maintain MUC2 expression in MCA cells.

Deconstructing Clinical Workflow: Identifying Teaching-Learning Principles for Barcode Electronic Medication Administration With Nursing Students.

The purpose of this quality improvement project was to better understand how to teach medication administration underpinned by an electronic medication administration record (eMAR) system used in simulated, prelicensure nursing education. Methods included a workflow and integration analysis and a detailed process mapping of both an oral and a sublingual medication administration. Procedural and curriculum development considerations related to medication administration using eMAR technology are presented for nurse educators.

Early identification of DPAM in at-risk low-grade appendiceal mucinous neoplasm patients: a new approach to surveillance for peritoneal metastasis.

Background: Disseminated peritoneal adenomucinosis (DPAM) patients often have a history of appendectomy with identification of an incidental mucinous neoplasm (low-grade appendiceal mucinous neoplasm (LAMN)). The rate of developing DPAM is not well established.

Methods: Twenty-two patients with incidental LAMN were identified and monitored with cancer markers and CT every 4-6 months.

Patient-derived xenograft mouse models of pseudomyxoma peritonei recapitulate the human inflammatory tumor microenvironment.

Pseudomyxoma peritonei (PMP) is a neoplastic syndrome characterized by peritoneal tumor implants with copious mucinous ascites. The standard of care for PMP patients is aggressive cytoreductive surgery performed in conjunction with heated intraperitoneal chemotherapy. Not all patients are candidates for these procedures and a majority of the patients will have recurrent disease.

Malignant Peritoneal Mesothelioma: Characterization of the Inflammatory Response in the Tumor Microenvironment.

Background: Malignant peritoneal mesothelioma (MPM) is a rare cancer arising from mesothelial cells lining the peritoneal surface. Little is known about the tumor microenvironment in regulating MPM oncogenesis. The current study defined the chemokine/cytokine expression profile and inflammatory responses within the MPM microenvironment.

Gastrointestinal Cancers With Peritoneal Carcinomatosis: Surgery and Hyperthermic Intraperitoneal Chemotherapy.

This review focuses on the underlying rationale for the use of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CS+HIPEC) in the treatment of patients with primary gastrointestinal tumors with metastatic peritoneal disease. It examines the advantages of CS+HIPEC in peritoneal cancers and explores the controversies surrounding this treatment. For low-grade cancers, such as pseudomyxoma peritonei, CS+HIPEC is standard of care.

Comparison of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with mitomycin or carboplatin for diffuse malignant peritoneal mesothelioma.

Diffuse malignant peritoneal mesothelioma is a rare, aggressive disease. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved outcomes where systemic chemotherapy has not succeeded. In this study, we compare outcomes of patients treated with mitomycin or carboplatin as perfusate.

Intraperitoneal chemotherapy for peritoneal surface malignancy: experience with 1,000 patients.

Background: Peritoneal dissemination of abdominal malignancy (carcinomatosis) has a clinical course marked by bowel obstruction and death; it traditionally does not respond well to systemic therapy and has been approached with nihilism. To treat carcinomatosis, we use cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods: A prospective database of patients has been maintained since 1992.

Proposed classification of pseudomyxoma peritonei: influence of signet ring cells on survival.

The nomenclature and classification of pseudomyxoma peritonei (PMP) is confusing and controversial. Numerous classification systems have been proposed, none of which are easily reproducible or a useful guide for treatment. Patients with PMP of appendiceal origin were identified from our institution's database.

Pseudomyxoma peritonei: inflammatory responses in the peritoneal microenvironment.

Background: Pseudomyxoma peritonei (PMP), a peritoneal mucinous neoplasm of appendiceal origin, is associated with inflammation and fibrosis, which is central to its biology. The significance of the microenvironment in PMP has not been well characterized.

Methods: Immunoassays were used to measure cytokines and C-reactive protein (CRP).

Kras mutations and p53 overexpression in pseudomyxoma peritonei: association with phenotype and prognosis.

Background: Little information exists on Kras mutations and p53 overexpression in pseudomyxoma peritonei (PMP). These genetic alterations are associated with poorer prognoses in colorectal cancer. We postulated that these mutations might be more frequent in high-grade (HG) PMP (peritoneal mucinous carcinomatosis) versus low-grade (LG) PMP (disseminated peritoneal adenomucinosis/peritoneal mucinous carcinomatosis), for which survival differences are well documented.

Right hemicolectomy is not routinely indicated in pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is primarily the result of a ruptured mucinous appendix neoplasm (MAN). Often MAN is lumped with but biologically distinct from intestinal appendiceal adenocarcinoma. Nodal and systemic dissemination are rare with the peritoneal cavity being the primary site of recurrence.

Determinants of outcomes in pancreatic surgery and use of hospital resources.

Background And Objectives: Outcomes for patients undergoing major pancreatic surgery have improved, but a subset of patients that significantly utilize more resources exists. Variables that can lead to an increase in resource utilization in patients undergoing pancreatic surgery were identified.

Methods: Patients undergoing pancreatic surgery for neoplasms were identified from the NSQIP database (2006-2008).

Clinical implications of novel activating EGFR mutations in malignant peritoneal mesothelioma.

Background: There is a paucity of information about the molecular perturbations involved in MPM tumor formation. We previously reported that EGFR-TK mutations in MPM were predictive of achieving optimal surgical cytoreduction, but the status of EGFR pathway activation potential of these mutations was not known. Here we present the mutant EGFR activating potential and the matured survival data of the EGFR mutant(mut+) relative to wild type EGFR(mut-) mesothelioma.

Hyperthermic intraperitoneal chemotherapy in ovarian cancer: first report of the HYPER-O registry.

Introduction: An analysis of experience of surgical and gynecologic oncologists in the United States with the use of hyperthermic intraperitoneal chemotherapy for women with invasive epithelial ovarian cancer (EOC).

Methods: An Internet-based registry (HYPER-O) collected data from collaborating institutions. Eligibility included women with EOC treated with hyperthermic intraperitoneal chemotherapy.

Novel and existing mutations in the tyrosine kinase domain of the epidermal growth factor receptor are predictors of optimal resectability in malignant peritoneal mesothelioma.

Malignant peritoneal mesotheliomas (MPM) are rare tumors representing 20% of all malignant mesothelioma cases. The median survival for these tumors is less than a year, and like other peritoneal surface malignancies, this is due primarily to intra-abdominal recurrence and progression. Currently there is a paucity of information about the biology of these tumors and molecular perturbations that are involved in tumor formation.

Low grade peritoneal mucinous carcinomatosis associated with human papilloma virus infection: case report.

Pseudomyxoma peritonei is a clinical syndrome characterized by peritoneal dissemination of a mucinous tumor with mucinous ascites. The vast majority of the pseudomyxoma peritonei are associated with mucinous neoplasms of the appendix. We describe a case of pseudomyxoma peritonei associated with mucinous adenocarcinoma of the cervix in a 60-year-old woman.

Peritoneal surface disease from colorectal cancer: comparison with the hepatic metastases surgical paradigm in optimally resected patients.

Background: Surgical resection is the treatment of choice for colorectal hepatic metastases (HM). In contrast, metastatic disease to the peritoneum is treated with systemic therapy. We examined our experience with cytoreductive surgery (CS) and intraperitoneal hyperthermic chemotherapy (IPHC) for peritoneal surface disease (PSD) compared with liver resection for HM.

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: experience with 501 procedures.

Background: Peritoneal dissemination of abdominal malignancy (PSD) has a clinical course marked by bowel obstruction and death. We have been using aggressive cytoreductive surgery with intraperitoneal hyperthermic chemotherapy (IPHC) to treat PSD. The purpose of this article was to review our experience with IPHC.

Mucin expression profile in Barrett's, dysplasia, adenocarcinoma sequence in the esophagus.

Background: The molecular events that accompany the progression to adenocarcinoma (ADC) of the esophagus are poorly understood. Aberrant mucin receptor expression can contribute to increased cell growth and metastatic ability.

Aim: The aim of this study was to establish a pattern for mucin (MUC) gene expression in the esophageal mucosa under normal and pathological conditions.

A variant of estrogen receptor-{alpha}, hER-{alpha}36: transduction of estrogen- and antiestrogen-dependent membrane-initiated mitogenic signaling.

The status of the 66-kDa human estrogen receptor-alpha (hER-alpha66) is a critical determinant in the assessment of the prognosis and in the design of treatment strategies of human breast cancer. Recently, we cloned the cDNA of an alternatively spliced variant of hER-alpha66, termed hER-alpha36; the predicted protein lacks both transcriptional activation domains of hER-alpha66 but retains its DNA-binding domain, partial dimerization, and ligand-binding domains and three potential myristoylation sites located near the N terminus. These findings thus predict that hER-alpha36 functions very differently from hER-alpha66 in response to estrogen signaling.