Cancer-Associated Fibroblast-Like Tumor Cells Remodel the Ewing Sarcoma Tumor Microenvironment.

Purpose: Despite limited genetic and histologic heterogeneity, Ewing sarcoma (EwS) tumor cells are transcriptionally heterogeneous and display varying degrees of mesenchymal lineage specification in vitro. In this study, we investigated if and how transcriptional heterogeneity of EwS cells contributes to heterogeneity of tumor phenotypes in vivo.

Experimental Design: Single-cell proteogenomic-sequencing of EwS cell lines was performed and integrated with patient tumor transcriptomic data.

Carcinoma-associated fibroblast-like tumor cells remodel the Ewing sarcoma tumor microenvironment.

Tumor heterogeneity is a major driver of cancer progression. In epithelial-derived malignancies, carcinoma-associated fibroblasts (CAFs) contribute to tumor heterogeneity by depositing extracellular matrix (ECM) proteins that dynamically remodel the tumor microenvironment (TME). Ewing sarcomas (EwS) are histologically monomorphous, mesenchyme-derived tumors that are devoid of CAFs.

The importance of fusion protein activity in Ewing sarcoma and the cell intrinsic and extrinsic factors that regulate it: A review.

Accumulating evidence shows that despite clonal origins tumors eventually become complex communities comprised of phenotypically distinct cell subpopulations. This heterogeneity arises from both tumor cell intrinsic programs and signals from spatially and temporally dynamic microenvironments. While pediatric cancers usually lack the mutational burden of adult cancers, they still exhibit high levels of cellular heterogeneity that are largely mediated by epigenetic mechanisms.

Collective metastasis: coordinating the multicellular voyage.

The metastatic process is arduous. Cancer cells must escape the confines of the primary tumor, make their way into and travel through the circulation, then survive and proliferate in unfavorable microenvironments. A key question is how cancer cells overcome these multiple barriers to orchestrate distant organ colonization.

Mechanisms of breast cancer metastasis.

Invasive breast cancer tends to metastasize to lymph nodes and systemic sites. The management of metastasis has evolved by focusing on controlling the growth of the disease in the breast/chest wall, and at metastatic sites, initially by surgery alone, then by a combination of surgery with radiation, and later by adding systemic treatments in the form of chemotherapy, hormone manipulation, targeted therapy, immunotherapy and other treatments aimed at inhibiting the proliferation of cancer cells. It would be valuable for us to know how breast cancer metastasizes; such knowledge would likely encourage the development of therapies that focus on mechanisms of metastasis and might even allow us to avoid toxic therapies that are currently used for this disease.

Optimal, Large-Scale Propagation of Mouse Mammary Tumor Organoids.

Tumor organoids mimic the architecture and heterogeneity of in vivo tumors and enable studies of collective interactions between tumor cells as well as with their surrounding microenvironment. Although tumor organoids hold significant promise as cancer models, they are also more costly and labor-intensive to cultivate than traditional 2D cell culture. We sought to identify critical factors regulating organoid growth ex vivo, and to use these observations to develop a more efficient organoid expansion method.

Regulation of Collective Metastasis by Nanolumenal Signaling.

Collective metastasis is defined as the cohesive migration and metastasis of multicellular tumor cell clusters. Disrupting various cell adhesion genes markedly reduces cluster formation and colonization efficiency, yet the downstream signals transmitted by clustering remain largely unknown. Here, we use mouse and human breast cancer models to identify a collective signal generated by tumor cell clusters supporting metastatic colonization.

FoxP1 "Tspans" Quiescence and Activation of Mammary Stem Cells.

Stem cells can enter a reversible cell-cycle arrest state termed quiescence. In this issue of Developmental Cell, Fu et al. report that the transcription factor FoxP1 is necessary for postnatal mammary gland development and relieves Tspan8-dependent quiescence in basal mammary stem cells.

Comparison of Flow Dynamics of Peripherally and Centrally Inserted Intravenous Catheters Using a Rapid Infusion System (ThermaCor 1200).

The inability to rapidly administer warm intravenous fluids and blood products can potentially threaten a patient's safety and well-being in many clinical settings. Large-bore intravenous catheters and rapid infusion systems are often used in situations where rapid blood loss and massive blood transfusion may be expected. This study examined the maximum flow rate and infusion pressure of various peripherally and centrally inserted intravenous catheters using a rapid infusion system (ThermaCor 1200 Rapid Infusion System, Smisson-Cartledge Biomedical).

Un(MaSC)ing Stem Cell Dynamics in Mammary Branching Morphogenesis.

The properties of stem cells that participate in mammary gland branching morphogenesis remain contested. Reporting in Nature, Scheele et al. (2017) establish a model for post-pubertal mammary branching morphogenesis in which position-dependent, lineage-restricted stem cells undergo cell mixing in order to contribute to long-term growth.

The seroprevalence of cysticercosis, malaria, and Trypanosoma cruzi among North Carolina migrant farmworkers.

A seroprevalence study of cysticercosis, Trypanosoma cruzi, and plasmodia species and screening for active malaria was conducted among a randomly selected group of 138 Hispanic and Haitian migrant farmworkers. A random sample of labor camps in eastern North Carolina was selected. Blood samples were tested by Indirect Fluorescent Antibody techniques for plasmodial antibody and by enzyme-linked immunosorbent assay (ELISA) for cysticerci and T.

Acute appendicitis in children with leukemia and other malignancies: still a diagnostic dilemma.

Of 6,099 children treated for malignancy, 16 (ages 3.5 to 18 years) developed acute appendicitis between 1962 and 1989. Fourteen had leukemia (ALL 10, AML 4).

Is there a role for laparoscopic appendectomy in pediatric surgery?

Although laparoscopic procedures are currently in vogue in general surgery, the role of this approach in children has not been prospectively evaluated in the United States using the new instrumentation now available to us. To assess the value of laparoscopic appendectomy (LA) in childhood, we prospectively compared 14 LAs with 50 open appendectomies (OA) over 6 months in a single children's hospital. Antibiotic usage was at the discretion of the surgeon regardless of the procedure performed and was not different between groups.

The effect of tube gastrostomy on gastroesophageal reflux in patients with esophageal atresia.

Gastroesophageal reflux (GER) occurs frequently in infants with esophageal atresia (EA). The definitive management is primary repair and often includes tube gastrostomy. The recent finding of lower esophageal sphincter (LES) pressure changes with tube gastrostomy suggests that GER might be related to gastrostomy rather than EA per se.

Neurenteric cyst: surgery and diagnostic imaging.

Neurenteric cysts are rare, with fewer than 30 cases noted in the literature. We report the case of a newborn infant with respiratory distress caused by a large neurenteric cyst that was identified by prenatal ultrasound. Treatment consisted of excision of the mass through a right posterolateral thoracotomy.

Late urologic complication of an abdominal gunshot wound.

An unusual late complication of an abdominal gunshot wound is presented. It consisted of an acute hydronephrosis of the left kidney by a BB-type bullet that migrated into the ureter of a 11-year-old boy 1 month after he was injured in the left flank, causing its complete obstruction. A percutaneous nephrostomy was performed and, with the help of a basket-type catheter, the bullet was removed.

Twenty-five years' experience with Hirschsprung's disease.

Sixty-three patients with biopsy-proven Hirschsprung's disease were diagnosed at LeBonheur Children's Medical Center, Memphis, TN between 1955 and 1980. Fifty-eight of these patients had pull-through procedures performed by three similarly trained pediatric surgeons. The follow-up was 100 percent, averaging 8 years from initial diagnosis.

Extralobar pulmonary sequestration and mediastinal bronchogenic cyst.

A child with coexisting mediastinal bronchogenic cyst and extralobar pulmonary sequestration is presented. Two distinct lesions were suggested by barium esophagram and confirmed by a chest computed tomography scan. The diagnostic and embryologic relationship of the two lesions is discussed.

The continued value of angiography in planning surgical resection of benign and malignant hepatic tumors in children.

We assessed the accuracy of angiography or digital subtraction angiography (DSA) in diagnosing malignancy in hepatic tumors in children. In addition, these results were correlated with sonographic and computed tomographic findings of the liver in selected patients. Twenty-seven patients with primary liver tumors were examined with celiac or selective hepatic arteriography.

Effective cisplatin (DDP) based chemotherapy in the treatment of hepatoblastoma.

Nine of 11 patients with hepatoblastoma treated with cisplatin (DDP) based chemotherapy had a complete (CR) or partial (PR) remission. Five of these patients had measurable pulmonary disease and four achieved a CR of pulmonary lesions. The average interval of disease control following DDP was three times that of Adriamycin (ADR).

Limb salvage procedures for children with osteosarcoma: an alternative to amputation.

Amputation remains the standard surgical management for patients with osteosarcoma. However, in carefully selected patients, eradication of the primary tumor can be achieved by En-Bloc resection of the affected bone preserving both anatomical and functional status. Our criteria for limb salvage procedures are that patients must: (1) be age 12 years or older, (2) have no angiographic or clinical evidence of neurovascular involvement, (3) have low-grade osteosarcoma and/or good response to preoperative chemotherapy, and (4) be compliant.

Transmedullary amputation and resection of metastases in combined therapy of osteosarcoma.

The eradication of microfoci of metastatic osteosarcoma by adjuvant chemotherapy permits the surgeon to take a more conservative approach to amputation and to more aggressively resect metastases. In a series of 59 children with osteosarcoma of an extremity, transmedullary amputation carried no greater risk of stump recurrence than either disarticulation or amputation above the joint. We attribute this to careful selection of the level of amputation by use of preoperative bone scans, intraoperative frozen sections of bone stump and intensive postoperative adjuvant chemotherapy.