Biomechanical regulation of drug sensitivity in an engineered model of human tumor.

Predictive testing of anticancer drugs remains a challenge. Bioengineered systems, designed to mimic key aspects of the human tumor microenvironment, are now improving our understanding of cancer biology and facilitating clinical translation. We show that mechanical signals have major effects on cancer drug sensitivity, using a bioengineered model of human bone sarcoma. Ewing sarcoma (ES) cells were studied within a three-dimensional (3D) matrix in a bioreactor providing mechanical loadings. Mimicking bone-like mechanical signals within the 3D model, we rescued the ERK1/2-RUNX2 signaling pathways leading to drug resistance. By culturing patient-derived tumor cells in the model, we confirmed the effects of mechanical signals on cancer cell survival and drug sensitivity. Analyzing human microarray datasets, we showed that RUNX2 expression is linked to poor survival in ES patients. Mechanical loadings that activated signal transduction pathways promoted drug resistance, stressing the importance of introducing mechanobiological cues into preclinical tumor models for drug screening.

A case report of concurrent embryonal rhabdomyosarcoma and diffuse large B-cell lymphoma in an adult without identifiable cancer predisposition.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. Rhabdomyosarcoma, the most common soft tissue sarcoma of childhood. makes up less than 1% of solid malignancies in adults with around 400 new cases each year in the United States. They have not previously been reported concurrently. CASE PRESENTATION: A 37 year old woman presented with painful enlarging leg mass. Biopsy of the mass was consistent with embryonal rhabdomyosarcoma. Staging imaging revealed a PET avid anterior mediastinal lymph node. Excisional biopsy of this mass was consistent with diffuse large B-cell lymphoma. Hybridization capture-based next-generation DNA sequencing did not reveal shared somatic tumor mutations. Germline analysis did not show identifiable aberrations of TP53 or other heritable cancer susceptibility genes. She was treated with a personalized chemotherapy regimen combining features of R-CHOP and Children's Oncology Group ARST 0331. CONCLUSIONS: This case illustrates a unique clinical entity successfully treated with a personalized chemotherapeutic regimen.

Diagnosis of typhoid fever by polymerase chain reaction.

OBJECTIVE: To determine the efficacy of nested polymerase chain reaction (PCR) in detecting Salmonella typhi gene sequences in blood and urine specimens and to determine the cut-off titer of Widal test using PCR as gold standard test for diagnosis of typhoid fever. METHODS: Study included 71 children between the ages of 8 months and 14 years; 52 of them were suspected cases of typhoid fever, 11 were febrile non-typhoid controls and 8 were apparently healthy children. Nested PCR in Blood and Urine, Blood culture, Widal test and Urine culture were done and their results analyzed. RESULTS: Among suspected typhoid cases, PCR in blood and urine had positivity of 82.7% each. Blood culture, Widal test (at cut off titer TO and/or TH > 1:160) and urine culture had positivity of 26.9%, 50% and 3.8% respectively. In one case, urine PCR was positive and blood PCR was negative. Similarly, in another case, PCR in blood was positive however urine tested negative. Considering PCR as gold standard, the antibody cut off titer was evaluated. A cut-off titer of TO > 1:80 and/or TH > 1:160 had sensitivity and specificity of 72.7% and 84.2%, while the respective figures were 50% and 89.5% when the cut-off titer was TO and/or TH > 1:160. CONCLUSION: The sensitivity, specificity, positive and negative predictive values, likelihood ratios were same for PCR based detection of S. typhi in blood and urine samples. Nested PCR had higher efficacy in detecting typhoid fever than Widal test, blood and urine cultures. A cut off titer of TO > 1:80 and/or TH > 1:160 was found to have better diagnostic value in this region.