SOX2 and PI3K Cooperate to Induce and Stabilize a Squamous-Committed Stem Cell Injury State during Lung Squamous Cell Carcinoma Pathogenesis.

Although cancers are considered stem cell diseases, mechanisms involving stem cell alterations are poorly understood. Squamous cell carcinoma (SQCC) is the second most common lung cancer, and its pathogenesis appears to hinge on changes in the stem cell behavior of basal cells in the bronchial airways. Basal cells are normally quiescent and differentiate into mucociliary epithelia.

Integrin α11β1 regulates cancer stromal stiffness and promotes tumorigenicity and metastasis in non-small cell lung cancer.

Integrin α11β1 is a stromal cell-specific receptor for fibrillar collagens and is overexpressed in carcinoma-associated fibroblasts (CAFs). We have investigated its direct role in cancer progression by generating severe combined immune deficient (SCID) mice deficient in integrin α11 (α11) expression. The growth of A549 lung adenocarcinoma cells and two patient-derived non-small cell lung carcinoma (NSCLC) xenografts in these α11 knockout (α11(-/-)) mice was significantly impeded, as compared with wild-type (α11(+/+)) SCID mice.

Appropriateness of using patient-derived xenograft models for pharmacologic evaluation of novel therapies for esophageal/gastro-esophageal junction cancers.

The high morbidity and mortality of patients with esophageal (E) and gastro-esophageal junction (GEJ) cancers, warrants new pre-clinical models for drug testing. The utility of primary tumor xenografts (PTXGs) as pre-clinical models was assessed. Clinicopathological, immunohistochemical markers (p53, p16, Ki-67, Her-2/neu and EGFR), and global mRNA abundance profiles were evaluated to determine selection biases of samples implanted or engrafted, compared with the underlying population.

Radiological images of keratocystoma: a rare tumor of the parotid gland.

A 34-year-old man found a mildly tender preauricular mass. Ultrasonography revealed an anechoic mass in the superficial lobe of the parotid gland. Magnetic resonance imaging showed thin ring-like contrast enhancement and homogenously high intensity on T2-weighted images.

Epidermal growth factor receptor mutation-specific immunohistochemical antibodies in lung adenocarcinoma.

Aims: We investigated the sensitivity and specificity of two novel Epidermal growth factor receptor (EGFR) mutation-specific antibodies in the detection of the most common EGFR mutations in lung adenocarcinoma.

Methods And Results: A total of 241 resected lung adenocarcinoma specimens and six resected post-neoadjuvant gefitinib adenocarcinomas were analysed for EGFR mutation using mass spectrometry, fragment analysis and direct PCR sequencing platforms. Tissue arrays and/or full sections of these cases were evaluated using immunohistochemistry with two novel antibodies (clones SP125 and SP111) and two previously reported antibodies (clones 43B2 and 6B6), specific for L858R or 15-nucleotide exon-19 deletion EGFR mutations.

Pooled analysis of the prognostic and predictive effects of KRAS mutation status and KRAS mutation subtype in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy.

Purpose: We undertook this analysis of KRAS mutation in four trials of adjuvant chemotherapy (ACT) versus observation (OBS) to clarify the prognostic/predictive roles of KRAS in non-small-cell lung cancer (NSCLC).

Methods: KRAS mutation was determined in blinded fashion. Exploratory analyses were performed to characterize relationships between mutation status and subtype and survival outcomes using a multivariable Cox model.

Molecular biology of normal melanocytes and melanoma cells.

Malignant melanoma is one of the most aggressive malignancies in humans and is responsible for 60-80% of deaths from skin cancers. The 5-year survival of patients with metastatic malignant melanoma is about 14%. Its incidence has been increasing in the white population over the past two decades.

Primary esophageal and gastro-esophageal junction cancer xenograft models: clinicopathological features and engraftment.

There are very few xenograft models available for the study of esophageal (E) and gastro-esophageal junction (GEJ) cancer. Using a NOD/SCID model, we implanted 90 primary E and GEJ tumors resected from patients and six endoscopic biopsy specimens. Of 69 resected tumors with histologically confirmed viable adenocarcinoma or squamous cell carcinoma, 22 (32%) was engrafted.

Glycogen synthase kinase-3 inhibition sensitizes pancreatic cancer cells to TRAIL-induced apoptosis.

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) induces apoptosis in a variety of cancer cell lines with little or no effect on normal cells. However, its effect is limited as some cancers including pancreatic cancer show de novo resistance to TRAIL induced apoptosis. In this study we report that GSK-3 inhibition using the pharmacologic agent AR-18, enhanced TRAIL sensitivity in a range of pancreatic and prostate cancer cell lines.

L1 cell adhesion molecule promotes tumorigenicity and metastatic potential in non-small cell lung cancer.

Purpose: Non-small cell lung cancer (NSCLC) is a highly metastatic cancer with limited treatment options, thus requiring development of novel targeted therapies. Our group previously identified L1 cell adhesion molecule (L1CAM) expression as a member of a prognostic multigene expression signature for NSCLC patients. However, there is little information on the biologic function of L1CAM in lung cancer cells.

Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer.

The tumor microenvironment strongly influences cancer development, progression, and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC.

From melanocyte to metastatic malignant melanoma.

Malignant melanoma is one of the most aggressive malignancies in human and is responsible for almost 60% of lethal skin tumors. Its incidence has been increasing in white population in the past two decades. There is a complex interaction of environmental (exogenous) and endogenous, including genetic, risk factors in developing malignant melanoma.

CD163 expression in leukemia cutis.

Background: Proper diagnosis of myeloid leukemia cutis (LC) is of great clinical importance but can be difficult because no single immunohistochemical marker is adequately sensitive or specific for definitive diagnosis. Thus, a broader panel of markers is often desirable. CD163 is highly specific for normal and neoplastic cells of the monocyte/histiocyte lineage.

D2-40, a novel immunohistochemical marker in differentiating dermatofibroma from dermatofibrosarcoma protuberans.

The distinction between dermatofibroma, particularly cellular variant, and dermatofibrosarcoma protuberans in excisional biopsies is usually straightforward. However, a separation between the two may be sometimes challenging, especially in superficial biopsies. Although factor XIIIa and CD34 immunostains are useful in differentiating dermatofibroma and dermatofibrosarcoma protuberans in most instances, focal CD34 positivity may be seen in cellular fibrous histiocytoma.

Co-overexpression of Met and hepatocyte growth factor promotes systemic metastasis in NCI-H460 non-small cell lung carcinoma cells.

Complete resection of early-stage non-small cell lung cancer (NSCLC) is potentially curative, yet approximately 50% of patients are at risk for developing metastatic recurrence. Met, the receptor for hepatocyte growth factor (HGF) is a receptor tyrosine kinase with demonstrated roles in regulating cellular proliferation, motility, morphogenesis, and apoptosis. Met receptor and its ligand, HGF, are commonly overexpressed in NSCLC, and their overexpression has been associated with poor prognosis, which could potentially involve a paracrine and/or autocrine activation loop.

Assessment of sentinel lymph node in cervical cancer: review of literature.

Sentinel lymph node biopsy is a novel method for the surgical management of patients with cervical cancer. Sentinel nodes have a higher chance of harbouring metastases than non-sentinel nodes. Assessment of sentinel nodes provides an opportunity to stage patients intraoperatively and avoid complete pelvic lymph node dissection and hence its morbidities.

Photodynamic molecular beacon triggered by fibroblast activation protein on cancer-associated fibroblasts for diagnosis and treatment of epithelial cancers.

Fibroblast activation protein (FAP) is a cell-surface serine protease highly expressed on cancer-associated fibroblasts of human epithelial carcinomas but not on normal fibroblasts, normal tissues, and cancer cells. We report herein a novel FAP-triggered photodynamic molecular beacon (FAP-PPB) comprising a fluorescent photosensitizer and a black hole quencher 3 linked by a peptide sequence (TSGPNQEQK) specific to FAP. FAP-PPB was effectively cleaved by both human FAP and murine FAP.

Blue nevi of the Müllerian tract: case series and review of the literature.

Background: Blue nevi are rare in the cervix and vagina. Melanocytes are not normally found in these sites and have been hypothesized to arise either from the Schwann cells of stromal nerves or from melanocytic precursors which have aberrantly migrated from the neural crest to rest in the Müllerian stroma. Because of their rarity (3 previous cases in the literature), vaginal blue nevi have not previously been studied with immunohistochemical and ultrastructural analysis.

Fatal subcutaneous panniculitis-like T-cell lymphoma with interface change and dermal mucin, a dead ringer for lupus erythematosus.

We report a 48-year-old man who presented with ulcerated plaques and nodules of the lower extremities. Skin biopsies revealed a dense lymphocytic infiltrate involving the dermis and the subcutis in a lobular and septal pattern. No overt cytological atypia was present.

Primary localized laryngeal amyloidosis: report of 3 cases with long-term follow-up and review of the literature.

Context: Localized laryngeal amyloidosis is an uncommon condition with limited long-term follow-up studies. The precise etiology and pathogenesis are not entirely clear.

Objective: To further characterize the histopathologic features and possible pathogenesis of localized laryngeal amyloidosis.