Large Metastatic Cancer Research Articles

VIRUSBreakend: Viral Integration Recognition Using Single Breakends.

MotivationIntegration of viruses into infected host cell DNA can cause DNA damage and disrupt genes. Recent cost reductions and growth of whole genome sequencing has produced a wealth of data in which viral presence and integration detection is possible. While key research and clinically relevant insights can be uncovered, existing software has not achieved widespread adoption, limited in part due to high computational costs, the inability to detect a wide range of viruses, as well as precision and sensitivity.ResultsHere, we describe VIRUSBreakend, a high-speed tool that identifies viral DNA presence and genomic integration. It utilizes single breakends, breakpoints in which only one side can be unambiguously placed, in a novel virus-centric variant calling and assembly approach to identify viral integrations with high sensitivity and a near-zero false discovery rate. VIRUSBreakend detects viral integrations anywhere in the host genome including regions such as centromeres and telomeres unable to be called by existing tools. Applying VIRUSBreakend to a large metastatic cancer cohort, we demonstrate that it can reliably detect clinically relevant viral presence and integration including HPV, HBV, MCPyV, EBV and HHV-8.Availability and implementationVIRUSBreakend is part of the Genomic Rearrangement IDentification Software Suite (GRIDSS). It is available under a GPLv3 license from https://github.com/PapenfussLab/VIRUSBreakend.Supplementary information Supplementary data are available at Bioinformatics online.

A Conjugate of Gemcitabine With Bisphosphonate (Gem/BP) Shows Potential as a Targeted Bone-Specific Therapeutic Agent in an Animal Model of Human Breast Cancer Bone Metastases

Bone metastases in advanced breast cancer patients remains a significant treatment challenge. Bisphosphonates are now a routine first line treatment for prevention and treatment of skeletal damage caused by malignancies and, moreover, have shown an ability to transport therapeutic drugs to the bone. Here, we describe the effect of a conjugate between the potent anticancer drug gemcitabine and a bisphosphonate molecule (Gem/BP) in an animal model of breast cancer metastases. We have previously demonstrated the targeting of this compound to bone in normal mice using an analog labeled with the radionuclide 99mTc. Using a bone metastasis model in nude mice produced by intracardiac injection of the human breast cancer cell line MDA-MB-231BO, we examined the effect of Gem/BP and gemcitabine in reducing the frequency and severity of osteolytic bone lesions. High-resolution radiographs and microPET images showed that Gem/ BP reduced the number and size of bone metastases relative to the gemcitabine-treated and the untreated control groups. Histological examination of the humeri and femurs of the control and gemcitabine groups revealed large metastatic cancer lesions in the outer and inner cortices and the medullary cavities. In contrast, Gem/BP-treated mice showed occasional small wedge-shaped metastases under the periosteum of the outer cortex and very occasionally in the medulla. These findings suggest that Gem/BP should be further evaluated for use in the treatment of bone metastases in breast cancer.

Extracorporeal Membrane Oxygenation as a Bridge to Definitive Airway Security in 3 Severe Acute Extrinsic Airway Compression Patients - A Case Report -

Extracorporeal membrane oxygenation (ECMO) has been used for cardiac and respiratory failure for over 30 years. Recently, however, ECMO has emerged as a useful means of short-term support in the management of hypoxic patients for nontraditional indications. Here, we report the use of veno-venous ECMO as a bridge to support a patient with severe airway obstruction because of tumor compression. Case 1: A patient with extrinsic airway compression secondary to a large metastatic cancer on neck was successfully managed using ECMO. Case 2: The successful use of ECMO to support a patient with extrinsic airway compression secondary to a recurred thyroid cancer. Case 3: A pregnant woman with airway obstruction secondary to metastatic lymphadenopathy of lung cancer who underwent successful tracheal stent insertion. The 3 patients were successfully weaned off ECMO without any complication. Although these conditions are uncommon indications, ECMO is a potential option for such life-threatening conditions.

Hepatic Resection for Large Hepatic Metastasis of Adrenocortical Carcinoma after Cyberknife Treatment

Surgical resection is the best treatment for operable metastatic liver cancer. Large metastatic cancer usually has low operability, so a debulking modality of mass is needed to increase operability. Chemotherapy and radiotherapy were commonly used as neoadjuvant treatments. Cyberknife stereotactic radiosurgery systems were only considered as one of the palliative treatment modalities for inoperable or surgically complex tumors. But, in this case, we applied Cyberknife as the preoperative debulking modality for large hepatic metastasis of adrenocortical carcinoma. After Cyberknife treatment 3 cycle×2,700 cGY, tumor size decreased (metastatic liver mass decreased to 15×9 cm from 19×12.5 cm, adrenal mass decreased to 5×3 cm from 7.4×4.5 cm). We could then resect the tumor completely by extended right hemihepatectomy & right adrenalectomy. A preoperative multidisciplinary approach, including chemotherapy and radiation therapy can be considered to increase operability. So, cyberknife can be considered an additional modality as a neoadjuvant radiotherapy. (J Korean Surg Soc 2010;79:S45-49)

A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes.

The adoptive transfer of tumor-infiltrating lymphocytes (TIL) expanded in interleukin-2 (IL-2) to mice bearing micrometastases from various types of tumors showed that TIL are 50 to 100 times more effective in their therapeutic potency than are lymphokine-activated killer (LAK) cells. Therefore the use of TIL was explored for the treatment of mice with large pulmonary and hepatic metastatic tumors that do not respond to LAK cell therapy. Although treatment of animals with TIL alone or cyclophosphamide alone had little impact, these two modalities together mediated the elimination of large metastatic cancer deposits in the liver and lung. The combination of TIL and cyclophosphamide was further potentiated by the simultaneous administration of IL-2. With the combination of cyclophosphamide, TIL, and IL-2, 100% of mice (n = 12) bearing the MC-38 colon adenocarcinoma were cured of advanced hepatic metastases, and up to 50% of mice were cured of advanced pulmonary metastases. Techniques have been developed to isolate TIL from human tumors. These experiments provide a rationale for the use of TIL in the treatment of humans with advanced cancer.