Combined systemic and hepatic artery infusion pump chemo-therapy as a liver-directed therapy for colorectal liver metastasis-review of literature and case discussion

Colorectal cancer (CRC) is the third most prevalent malignancy and the second most common cause of death in the US. Liver is the most common site of colorectal metastases. About 13% of patients with colorectal cancer have liver metastasis on initial presentation and 50% develop them during the disease course. Although systemic chemotherapy and immunotherapy are the mainstay treatment for patients with metastatic disease, for selected patients with predominant liver metastasis, liver-directed approaches may provide prolonged disease control when combined with systemic treatments. Hepatic artery infusion pump (HAIP) chemotherapy is an approach which allows direct infusion of chemotherapeutic into the liver and is especially useful in the setting of multifocal liver metastases. When combined with systemic chemotherapy, HAIP improves the response rate, provides more durable disease control, and in some patients leads to successful resection. To ensure safety, use of HAIP requires multidisciplinary collaboration between interventional radiologists, medical oncologists, hepatobiliary surgeons and treatment nurses. Here, we review the benefits and potential risks with this approach and provide our single institution experience on two CRC patients successfully treated with HAIP in combination with systemic chemotherapy. We provide our recommendations in adopting this technique in the current era for patient with colorectal liver metastases

Establishment of novel neuroendocrine carcinoma patient-derived xenograft models for receptor peptide-targeted therapy

Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare cancers consisting of neuroendocrine carcinomas (NECs) and neuroendocrine tumors (NETs), which have been increasing in incidence in recent years. Few cell lines and pre-clinical models exist for studying GEP NECs and NETs, limiting the ability to discover novel imaging and treatment modalities. To address this gap, we isolated tumor cells from cryopreserved patient GEP NECs and NETs and injected them into the flanks of immunocompromised mice to establish patient-derived xenograft (PDX) models. Two of six mice developed tumors (NEC913 and NEC1452). Over 80% of NEC913 and NEC1452 tumor cells stained positive for Ki67. NEC913 PDX tumors expressed neuroendocrine markers such as chromogranin A (CgA), synaptophysin (SYP), and somatostatin receptor-2 (SSTR2), whereas NEC1452 PDX tumors did not express SSTR2. Exome sequencing revealed loss o

Primordial nucleosynthesis and hadronic decay of a massive particle with a relatively short lifetime

In this paper we consider the effects on big bang nucleosynthesis (BBN) of the hadronic decay of a long-lived massive particle. If high-energy hadrons are emitted near the BBN epoch ($t \sim 10^{-2}$ -- $10^2 \sec$), they extraordinarily inter-convert the background nucleons each other even after the freeze-out time of the neutron to proton ratio. Then, produced light element abundances are changed, and that may result in a significant discrepancy between standard BBN and observations. Especially on the theoretical side, now we can obtain a lot of experimental data of hadrons and simulate the hadronic decay process executing the numerical code of the hadron fragmentation even in the high energy region where we have no experimental data. Using the light element abundances computed in the hadron-injection scenario, we derive a constraint on properties of such a particle by comparing our theoretical results with observations.Comment: 33 pages, 14 postscript figures, reference added, typo corrected, to appear in Phys. Rev.

Priorities to promote participant engagement in the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network

BACKGROUND: Engaging diverse populations in cancer genomics research is of critical importance and is a fundamental goal of the NCI Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Established as part of the Cancer Moonshot, PE-CGS is a consortium of stakeholders including clinicians, scientists, genetic counselors, and representatives of potential study participants and their communities. Participant engagement is an ongoing, bidirectional, and mutually beneficial interaction between study participants and researchers. PE-CGS sought to set priorities in participant engagement for conducting the network\u27s research. METHODS: PE-CGS deliberatively engaged its stakeholders in the following four-phase process to set the network\u27s research priorities in participant engagement: (i) a brainstorming exercise to elicit potential priorities; (ii) a 2-day virtual meeting to discuss priorities; (iii) recommendations from the PE-CGS External Advisory Panel to refine priorities; and (iv) a virtual meeting to set priorities. RESULTS: Nearly 150 PE-CGS stakeholders engaged in the process. Five priorities were set: (i) tailor education and communication materials for participants throughout the research process; (ii) identify measures of participant engagement; (iii) identify optimal participant engagement strategies; (iv) understand cancer disparities in the context of cancer genomics research; and (v) personalize the return of genomics findings to participants. CONCLUSIONS: PE-CGS is pursuing these priorities to meaningfully engage diverse and underrepresented patients with cancer and posttreatment cancer survivors as participants in cancer genomics research and, subsequently, generate new discoveries. IMPACT: Data from PE-CGS will be shared with the broader scientific community in a manner consistent with participant informed consent and community agreement

Tumor-on-chip modeling of organ-specific cancer and metastasis

Every year, cancer claims millions of lives around the globe. Unfortunately, model systems that accurately mimic human oncology - a requirement for the development of more effective therapies for these patients - remain elusive. Tumor development is an organ-specific process that involves modification of existing tissue features, recruitment of other cell types, and eventual metastasis to distant organs. Recently, tissue engineered microfluidic devices have emerged as a powerful in vitro tool to model human physiology and pathology with organ-specificity. These organ-on-chip platforms consist of cells cultured in 3D hydrogels and offer precise control over geometry, biological components, and physiochemical properties. Here, we review progress towards organ-specific microfluidic models of the primary and metastatic tumor microenvironments. Despite the field\u27s infancy, these tumor-on-chip models have enabled discoveries about cancer immunobiology and response to therapy. Future work should focus on the development of autologous or multi-organ systems and inclusion of the immune system

Solar Neutrino Constraints on the BBN Production of Li

Using the recent WMAP determination of the baryon-to-photon ratio, 10^{10} \eta = 6.14 to within a few percent, big bang nucleosynthesis (BBN) calculations can make relatively accurate predictions of the abundances of the light element isotopes which can be tested against observational abundance determinations. At this value of \eta, the Li7 abundance is predicted to be significantly higher than that observed in low metallicity halo dwarf stars. Among the possible resolutions to this discrepancy are 1) Li7 depletion in the atmosphere of stars; 2) systematic errors originating from the choice of stellar parameters - most notably the surface temperature; and 3) systematic errors in the nuclear cross sections used in the nucleosynthesis calculations. Here, we explore the last possibility, and focus on possible systematic errors in the He3(\alpha,\gamma)Be7 reaction, which is the only important Li7 production channel in BBN. The absolute value of the cross section for this key reaction is known relatively poorly both experimentally and theoretically. The agreement between the standard solar model and solar neutrino data thus provides additional constraints on variations in the cross section (S_{34}). Using the standard solar model of Bahcall, and recent solar neutrino data, we can exclude systematic S_{34} variations of the magnitude needed to resolve the BBN Li7 problem at > 95% CL. Additional laboratory data on He3(\alpha,\gamma)Be7 will sharpen our understanding of both BBN and solar neutrinos, particularly if care is taken in determining the absolute cross section and its uncertainties. Nevertheless, it already seems that this ``nuclear fix'' to the Li7 BBN problem is unlikely; other possible solutions are briefly discussed.Comment: 21 pages, 3 ps figure

Advances in modeling the immune microenvironment of colorectal cancer

Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related death in the US. CRC frequently metastasizes to the liver and these patients have a particularly poor prognosis. The infiltration of immune cells into CRC tumors and liver metastases accurately predicts disease progression and patient survival. Despite the evident influence of immune cells in the CRC tumor microenvironment (TME), efforts to identify immunotherapies for CRC patients have been limited. Here, we argue that preclinical model systems that recapitulate key features of the tumor microenvironment-including tumor, stromal, and immune cells; the extracellular matrix; and the vasculature-are crucial for studies of immunity in the CRC TME and the utility of immunotherapies for CRC patients. We briefly review the discoveries, advantages, and disadvantages of curren