A luminescent sensor for investigating serotonin metabolism in neuroendocrine cancer.

Background: Serotonin is emerging as a promising therapeutic target in tryptophan hydroxylase 1-positive tumors, but further mechanistic studies are needed to effectively target dysregulated serotonin metabolism. One challenge is a lack of methods for studying the dynamic nature of serotonin metabolism. Here, we report the development of a genetically encoded luminescent biosensor, termed iSero-Rluc, for the real-time detection of serotonin in live cells.

Larotrectinib in Mismatch-Repair-Deficient TRK Fusion-Positive Metastatic Colon Cancer After Progression on Immunotherapy.

A 43-year-old woman presented with recurrent metastatic colon cancer with metastases to the peritoneum after having initially been diagnosed with stage IIB colon cancer and deferring adjuvant chemotherapy. Circulating tumor DNA (ctDNA)-based liquid biopsy testing revealed microsatellite instability-high (MSI-H) status, which was also confirmed on tissue testing. This patient then underwent four cycles of pembrolizumab and two cycles of ipilimumab and nivolumab (CTLA-4 rescue) with, unfortunately, progression of the disease.

Expression of cancer stem cell markers in tall cell variant papillary thyroid cancer identifies a molecular profile predictive of recurrence in classic papillary thyroid cancer.

Background: Tall cell variant of papillary thyroid carcinoma is an aggressive subtype of papillary thyroid carcinoma. We examined expression of cancer stem cell markers in tall cell variant compared with other well-differentiated thyroid cancers.

Methods: Expression of cancer stem cell markers was examined in 572 thyroid tumors from The Cancer Genome Atlas Thyroid Cancer database and tall cell variant and papillary thyroid carcinoma tumors by immunohistochemistry.

Rapid and Sensitive Detection of Breast Cancer Cells in Patient Blood with Nuclease-Activated Probe Technology.

A challenge for circulating tumor cell (CTC)-based diagnostics is the development of simple and inexpensive methods that reliably detect the diverse cells that make up CTCs. CTC-derived nucleases are one category of proteins that could be exploited to meet this challenge. Advantages of nucleases as CTC biomarkers include: (1) their elevated expression in many cancer cells, including cells implicated in metastasis that have undergone epithelial-to-mesenchymal transition; and (2) their enzymatic activity, which can be exploited for signal amplification in detection methods.

Preclinical Evaluation of Cathepsin-Based Fluorescent Imaging System for Cytoreductive Surgery.

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal surface malignancies. The ability to detect microscopic foci of peritoneal metastasis intraoperatively may ensure the completeness of cytoreduction. In this study, we evaluated the suitability of a hand-held cathepsin-based fluorescent imaging system for intraoperative detection of appendiceal and colorectal peritoneal metastasis.

Molecular Predictors of Radiotherapy Response in Sarcoma.

Soft-tissue sarcoma is one of the few clinical cancer models in which pre-operative radiotherapy is commonly utilized and in which tumor response to radiotherapy could be assessed. However, clinical and histopathological features of soft-tissue sarcomas are not useful in predicting tumor radiotherapy response. Exploration of predictive markers of sarcoma response to radiotherapy is further confounded by discordance between radiological tumor size reduction, pathological changes, and clinical local recurrence rates.

XPO1 Inhibition Enhances Radiation Response in Preclinical Models of Rectal Cancer.

Purpose: Combination of radiation with radiosensitizing chemotherapeutic agents improves outcomes for locally advanced rectal cancer. Current treatment includes 5-fluorouracil-based chemoradiation prior to surgical resection; however pathologic complete response varies from 15% to 20%, prompting the need to identify new radiosensitizers. Exportin 1 (XPO1, also known as chromosome region 1, CRM1) mediates the nuclear export of critical proteins required for rectal cancer proliferation and treatment resistance.

False-negative rate of combined mammography and ultrasound for women with palpable breast masses.

Mammography and ultrasound are often used concurrently for patients with palpable breast masses. While mammography has a false-negative rate of approximately 15 %, the addition of breast ultrasound decreases this rate among patients with palpable breast masses. There are no recent outcome data regarding the use of combined reporting of ultrasound and mammography (CRUM) for palpable breast masses.

A critical look at local-regional management of peritoneal metastasis.

For patients with stage IV colorectal cancer, the presence of peritoneal metastases is a poor prognostic feature. Despite the improvement in systemic therapy, long-term survival remains poor for patients with peritoneal carcinomatosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be associated with long-term survival in patients who have limited peritoneal disease, particularly those who can have complete cytoreduction.

Global analysis of neutrophil responses to Neisseria gonorrhoeae reveals a self-propagating inflammatory program.

An overwhelming neutrophil-driven response causes both acute symptoms and the lasting sequelae that result from infection with Neisseria gonorrhoeae. Neutrophils undergo an aggressive opsonin-independent response to N. gonorrhoeae, driven by the innate decoy receptor CEACAM3.

Gram negative bacteria increase non-small cell lung cancer metastasis via Toll-like receptor 4 activation and mitogen-activated protein kinase phosphorylation.

Surgery is required for the curative treatment of lung cancer but is associated with high rates of postoperative pneumonias predominantly caused by gram negative bacteria. Recent evidence suggests that these severe infectious complications may decrease long term survival after hospital discharge via cancer recurrence, but the mechanism is unclear. Lung cancer cells have recently been demonstrated to express Toll-like receptors (TLR) that mediate pathogen recognition.

Lipopolysaccharide-induced toll-like receptor 4 signaling enhances the migratory ability of human esophageal cancer cells in a selectin-dependent manner.

Background: Esophageal cancer is an aggressive malignancy, and emerging data suggest that postoperative infections may promote cancer progression. Systemic exposure to lipopolysaccharide (LPS), a Gram-negative bacterial antigen involved in such infections, has been shown to increase cancer cell adhesion to the hepatic sinusoids in vivo. We investigated the direct impact of LPS on the migratory ability of esophageal cancer cells via the LPS receptor toll-like receptor 4 (TLR4).

The impact of incidental gastrointestinal stromal tumours on patients undergoing resection of upper gastrointestinal neoplasms.

Background: Emerging data suggest asymptomatic gastrointestinal stromal tumours (GISTs) of the upper gastrointestinal (UGI) tract are not uncommon. We sought to determine their incidence in patients undergoing resection for UGI neoplasms and their impact on surgical and adjuvant treatment.

Methods: We accessed a database prospectively listing all patients undergoing resection of non-GIST neoplasms of the stomach and esophagus at a single university centre over a 4.

Massive upper gastrointestinal bleeding secondary to duodenal metastasis of transitional cell carcinoma of the urinary bladder.

Acute upper gastrointestinal (UGI) bleeding is a common problem in our clinical practice and is often due to peptic ulcer diseases. Occasionally, malignancy may be implicated in these situations. Here we report a rare case of UGI bleeding secondary to metastatic transitional cell carcinoma (TCC) of the urinary bladder.

LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis.

Infectious complications resulting from resection of colorectal cancer (CRC) elevates the risk of cancer recurrence and metastasis, but the reason for this risk relationship is unknown. Defining the mechanisms responsible may offer opportunities to improve outcomes in a majority of patients whose tumors are resected as part of their therapy. The complex formed between Toll receptor TLR4 and myeloid differentiation factor MD2 defines a major cell surface receptor for lipopolysaccharide (LPS), a gram-negative bacterial antigen that has been implicated in infectious complications after CRC resection.

Renal matrix stone managed by ureteroscopic holmium laser lithotripsy.

Introduction: Matrix stones are rare types of urinary calculi composed of mucoproteins and mucopolysaccharides. Since isolated flank pain may be the only presenting symptom and routine radiographic studies are usually non-informative, diagnosis of such urinary calculi represents a clinical challenge. Traditionally, these matrix stones have been managed by either open pyelolithotomy or percutaneous nephrolithotomy (PCNL).

Crohn's disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM.

Abnormal expression of CEACAM6 is observed at the apical surface of the ileal epithelium in Crohn's disease (CD) patients, and CD ileal lesions are colonized by pathogenic adherent-invasive Escherichia coli (AIEC). We investigated the ability of AIEC reference strain LF82 to colonize the intestinal mucosa and to induce inflammation in CEABAC10 transgenic mice expressing human CEACAMs. AIEC LF82 virulent bacteria, but not nonpathogenic E.

Colorectal hyperplasia and dysplasia due to human carcinoembryonic antigen (CEA) family member expression in transgenic mice.

CEA and CEACAM6 are immunoglobulin family intercellular adhesion molecules that are up-regulated without structural mutations in approximately 70% of human cancers. Results in in vitro systems showing tumorigenic effects for these molecules suggest that this correlation could indicate an instrumental role in tumorigenesis. To test whether this applies in vivo, transgenic mice harboring 187 kb of the human genome containing four CEA family member genes including the CEA and CEACAM6 genes were created and their copy numbers increased by mating until colonocyte expression levels reached levels seen in human colorectal carcinomas.

Increased colon tumor susceptibility in azoxymethane treated CEABAC transgenic mice.

Human carcinoembryonic antigen (CEA), a widely used clinical tumor marker, and its close relative, CEACAM6, are often overexpressed in many cancers. This correlation suggests a possible instrumental role in tumorigenesis, which is supported by extensive results obtained with several in vitro systems. The implication that these results could also apply in vivo warrants investigation.

Novel mouse model for carcinoembryonic antigen-based therapy.

Many novel cancer therapies, including immunotherapy and gene therapy, are specifically targeted to tumor-associated molecules, among which carcinoembryonic antigen (CEA) represents a popular example. Discrepancies between preclinical experimental data in animal models and clinical outcome in terms of therapeutic response and toxicity, however, often arise. Preclinical testing can be compromised by the lack of CEA and other closely related human CEA family members in rodents, which lack analogous genes for most human CEA family members.