Scaffolding Protein Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) Regulates MAPK Inhibition Responsiveness in Pancreas Cancer via Crosstalk with AKT Signaling.

Unlabelled: Combinatorial molecular therapy in pancreatic ductal adenocarcinoma (PDAC) has yielded largely disappointing results in clinical testing to-date as a multitude of adaptive resistance mechanisms is making selection of patients via molecular markers that capture essential, intersecting signaling routes challenging. Here, we report the scaffolding protein connector enhancer of kinase suppressor of Ras 1 (CNKSR1) as mediator of resistance to MAPK (MEK) inhibition. MEK inhibition in CNKSR1high cancer cells induces translocation of CNKSR1 to the plasma membrane where the scaffolding protein interacts with and stabilizes the phosphorylated form of AKT.

Secondary Malignancies: The Cost of Progress.

Background: With advances in treatment of cancer, patients who survive their first malignancy are at risk of developing additional malignancies. Data on the risks of secondary malignancies after treatment of some of the more common cancers are lacking.

Methods: Our prospectively maintained database was queried from 1996 to 2016 to identify patients with breast cancer, colorectal cancer, melanoma, sarcoma, gastric, and pancreatic adenocarcinoma who developed additional malignancies.

Associations of CDH1 germline variant location and cancer phenotype in families with hereditary diffuse gastric cancer (HDGC).

Introduction: Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome associated with variants in E-cadherin (CDH1), diffuse gastric cancer and lobular breast cancer. There is considerable heterogeneity in its clinical manifestations. This study aimed to determine associations between CDH1 germline variant status and clinical phenotypes of HDGC.

Underuse of exon mutational analysis for gastrointestinal stromal tumors.

Background: Tyrosine kinase inhibitors (TKI) have become the guideline-recommended therapy for high-risk resected and advanced gastrointestinal stromal tumors (GISTs). Exon mutational analysis (EMA) is used to inform pretherapy response to TKI and may predict overall prognosis. Despite these benefits, EMA remains underused, and its impact on TKI therapy decision-making remains unexplored.

Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis.

Metastasis remains a leading cause of cancer mortality due to the lack of specific inhibitors against this complex process. To identify compounds selectively targeting the metastatic state, we used the perinucleolar compartment (PNC), a complex nuclear structure associated with metastatic behaviors of cancer cells, as a phenotypic marker for a high-content screen of over 140,000 structurally diverse compounds. Metarrestin, obtained through optimization of a screening hit, disassembles PNCs in multiple cancer cell lines, inhibits invasion in vitro, suppresses metastatic development in three mouse models of human cancer, and extends survival of mice in a metastatic pancreatic cancer xenograft model with no organ toxicity or discernable adverse effects.

The Changing Paradigm of Management of Liver Abscesses in Chronic Granulomatous Disease.

Background: Chronic granulomatous disease (CGD) is a rare genetic disorder causing recurrent infections. More than one-quarter of patients develop hepatic abscesses and liver dysfunction. Recent reports suggest that disease-modifying treatment with corticosteroids is effective for these abscesses.

Gastric Adenocarcinoma: A Multimodal Approach.

Despite its declining incidence, gastric cancer (GC) remains a leading cause of cancer-related deaths worldwide. A multimodal approach to GC is critical to ensure optimal patient outcomes. Pretherapy fine resolution contrast-enhanced cross-sectional imaging, endoscopic ultrasound and staging laparoscopy play an important role in patients with newly diagnosed ostensibly operable GC to avoid unnecessary non-therapeutic laparotomies.

Expression of the scaffold connector enhancer of kinase suppressor of Ras 1 (CNKSR1) is correlated with clinical outcome in pancreatic cancer.

Background: Despite the near universal occurrence of activating codon 12 KRAS somatic variants in pancreatic cancer, there is considerable heterogeneity in the molecular make-up, MAPK/ERK pathway activation states, and clinical outcome in this disease. We analyzed the expression levels of CNKSR1, a scaffold that influences MAPK/ERK pathway activity, in clinical pancreas cancer specimens and their impact on survival of patients with pancreatic cancer.

Methods: Immunohistochemical staining for CNKSR1 expression was performed on 120 specimens from three independent pancreatic cancer tissue registries, phospho-ERK levels were measured in 86 samples.

Why Do Long-Distance Travelers Have Improved Pancreatectomy Outcomes?

Background: Centralization of complex surgical care has led patients to travel longer distances. Emerging evidence suggested a negative association between increased travel distance and mortality after pancreatectomy. However, the reason for this association remains largely unknown.

Thoracic Surgery in Chronic Granulomatous Disease: a 25-Year Single-Institution Experience.

Introduction: Chronic granulomatous disease (CGD) is a genetic disorder in which phagocyte dysfunction leads to recurrent infection. Persistent pulmonary infections sometimes require thoracic surgical intervention. We reviewed our 25-year experience to identify outcomes and prognostic factors associated with thoracic surgery in these patients.

Approach to the surgical management of resectable gastric cancer.

The rates of gastric cancer, which is the third leading cause of cancer-related deaths worldwide, vary depending on geographic location. Margin-negative gastrectomy and adequate lymphadenectomy (removal of ≥15 lymph nodes) are the cornerstones of multimodal treatment for operable gastric cancer. Diagnostic laparoscopy should be included in the armamentarium for newly diagnosed gastric cancer in order to overcome the limitations of cross-sectional imaging in identifying sub-radiographic hepatic or peritoneal metastases.

Approach to the surgical management of resectable gastric cancer.

The rates of gastric cancer, which is the third leading cause of cancer-related deaths worldwide, vary depending on geographic location. Margin-negative gastrectomy and adequate lymphadenectomy (removal of ≥15 lymph nodes) are the cornerstones of multimodal treatment for operable gastric cancer. Diagnostic laparoscopy should be included in the armamentarium for newly diagnosed gastric cancer in order to overcome the limitations of cross-sectional imaging in identifying sub-radiographic hepatic or peritoneal metastases.

Common nerve decompressions of the upper extremity: reliable exposure using shorter incisions.

Unlabelled: Considering that several different specialties perform nerve decompressions in the upper extremity, universal technical standards do not exist. Many of these procedures are performed via incisions that are made unnecessarily long to achieve adequate exposure of the nerves and their known anatomical compression points. The purpose of this article is to introduce reproducible techniques that reliably allow the necessary anatomical exposure while minimizing the length of required skin incisions.

PCPH/ENTPD5 expression confers to prostate cancer cells resistance against cisplatin-induced apoptosis through protein kinase Calpha-mediated Bcl-2 stabilization.

Prostate cancer (PCa) frequently develops antiapoptotic mechanisms and acquires resistance to anticancer drugs. Therefore, identifying PCa drug resistance determinants should facilitate designing more effective chemotherapeutic regimens. Recently, we described that the PCPH protein becomes highly expressed in human prostatic intraepithelial neoplasia and in PCa, and that the functional interaction between PCPH and protein kinase Cdelta (PKCdelta) increases the invasiveness of human PCa.