Integrated Workflow for the Label-Free Isolation and Genomic Analysis of Single Circulating Tumor Cells in Pancreatic Cancer.

As pancreatic cancer is the third deadliest cancer in the U.S., the ability to study genetic alterations is necessary to provide further insight into potentially targetable regions for cancer treatment. Circulating tumor cells (CTCs) represent an especially aggressive subset of cancer cells, capable of causing metastasis and progressing the disease. Here, we present the Labyrinth-DEPArray pipeline for the isolation and analysis of single CTCs. Established cell lines, patient-derived CTC cell lines and freshly isolated CTCs were recovered and sequenced to reveal single-cell copy number variations (CNVs). The resulting CNV profiles of established cell lines showed concordance with previously reported data and highlight several gains and losses of cancer-related genes such as FGFR3 and GNAS. The novel sequencing of patient-derived CTC cell lines showed gains in chromosome 8q, 10q and 17q across both CTC cell lines. The pipeline was used to process and isolate single cells from a metastatic pancreatic cancer patient revealing a gain of chromosome 1q and a loss of chromosome 5q. Overall, the Labyrinth-DEPArray pipeline offers a validated workflow combining the benefits of antigen-free CTC isolation with single cell genomic analysis.

Circulating tumor cells in precision medicine: challenges and opportunities.

The mutational and phenotypic landscape of tumors is dynamic, requiring constant monitoring of cancer patients to provide the most up-to-date and effective care. Circulating tumor cells (CTCs) obtained via liquid biopsy can provide tumor DNA, RNA, and protein information that can aid in the diagnosis, prognosis, and treatment of patients. There have been many recent studies and advances in using CTC enumeration, characterization, and expansion to provide personalized cancer treatment, validating the benefit of using CTCs as a biomarker in standard of care procedures. In this paper, we aim to summarize these advances, their limitations, and suggest future areas of study necessary to bring CTC analysis to clinics.

Quantum Oscillator Noise Spectroscopy via Displaced Cat States.

Quantum harmonic oscillators are central to many modern quantum technologies. We introduce a method to determine the frequency noise spectrum of oscillator modes through coupling them to a qubit with continuously driven qubit-state-dependent displacements. We reconstruct the noise spectrum using a series of different drive phase and amplitude modulation patterns in conjunction with a data-fusion routine based on convex optimization. We apply the technique to the identification of intrinsic noise in the motional frequency of a single trapped ion with sensitivity to fluctuations at the sub-Hz level in a spectral range from quasi-dc up to 50 kHz.

Towards fully commercial, UV-compatible fiber patch cords.

We present and analyze two pathways to produce commercial optical-fiber patch cords with stable long-term transmission in the ultraviolet (UV) at powers up to ~ 200 mW, and typical bulk transmission between 66-75 %. Commercial fiber patch cords in the UV are of great interest across a wide variety of scientific applications ranging from biology to metrology, and the lack of availability has yet to be suitably addressed. We provide a guide to producing such solarization-resistant, hydrogen-passivated, polarization-maintaining, connectorized and jacketed optical fibers compatible with demanding scientific and industrial applications. Our presentation describes the fabrication and hydrogen loading procedure in detail and presents a high-pressure vessel design, calculations of required H2 loading times, and information on patch cord handling and the mitigation of bending sensitivities. Transmission at 313 nm is measured over many months for cumulative energy on the fiber output of > 10 kJ with no demonstrable degradation due to UV solarization, in contrast to standard uncured fibers. Polarization sensitivity and stability are characterized yielding polarization extinction ratios between 15 dB and 25 dB at 313 nm, where we find patch cords become linearly polarizing. We observe that particle deposition at the fiber facet induced by high-intensity UV exposure can (reversibly) deteriorate patch cord performance and describe a technique for nitrogen purging of fiber collimators which mitigates this phenomenon.

Primary angiosarcoma of the ovary: a case report of Stage I disease.

BACKGROUND: There are 20 documented cases of primary ovarian angiosarcoma. Most patients present with metastatic disease and respond poorly to chemotherapy. There is little information available to counsel early-staged patients on the need for or efficacy of adjuvant chemotherapy. CASE: We present a case of Stage Ic primary ovarian angiosarcoma treated with 3 cycles of adjuvant MAID chemotherapy. The patient is without evidence of disease 10 months post-operatively. CONCLUSION: A review of the literature indicates a potential role for MAID chemotherapy in the treatment of ovarian angiosarcomas. Detection of Stage I disease appears to confer a better prognosis regardless of the utilization of adjuvant chemotherapy.

Differences in symptoms between patients with benign and malignant ovarian neoplasms.

OBJECTIVE: The purpose of this study was to determine the symptoms that are experienced by patients who receive a diagnosis of early ovarian cancer and to compare those symptoms with the symptoms that are experienced by patients with late ovarian cancer, borderline ovarian cancer, and benign ovarian neoplasms. STUDY DESIGN: This study used a retrospective case-control design. Cases of invasive and borderline ovarian cancer (n=147 patients) were compared with 76 patients with benign ovarian neoplasms. RESULTS: Patients with early ovarian cancer were significantly more likely to have symptoms of mass effect (urinary frequency, constipation, palpable mass, pelvic pressure) compared with patients with benign ovarian neoplasms (67% vs 15%; P <.001), late stage disease (67% vs 40%; P =.008), and borderline cancer (67% vs 33%; P =.007). CONCLUSION: Mass effect symptoms were the only symptoms that differentiated patients with early-stage ovarian cancer from all other groups of patients. However, one third of the patients with early ovarian cancer did not report any of these symptoms.

A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study.

OBJECTIVES: Docetaxel is an inhibitor of microtubule depolymerization and has demonstrated activity in paclitaxel-resistant breast cancer and gynecologic cancer. The Gynecologic Oncology Group (GOG) conducted a study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma to determine its activity, and nature and degree of toxicity, in this cohort of patients. METHODS: Patients with platinum- and paclitaxel-resistant ovarian or peritoneal carcinoma, defined as progression while on or within 6 months of therapy, were eligible if they had measurable disease and had not received more than one chemotherapy regimen. Docetaxel at a dose of 100 mg/m(2) was administered iv over 1 h every 21 days. A prophylactic regimen of oral dexamethasone 8 mg bid was begun 24 h before docetaxel administration and continued for 48 h thereafter. Hepatic function was strictly monitored. RESULTS: Sixty patients were entered and treated with a total of 256 courses, with all 60 evaluable for toxicity and 58 evaluable for response. Responses were observed in 22.4% of patients, with 5.2% achieving complete response and 17.2% achieving partial response (95% CI, 12.5-35.3%). The median duration of response was 2.5 months. The likelihood of observing a response did not appear to be related to the length of the prior paclitaxel-free interval or duration of prior paclitaxel infusions. The principal adverse effect of grade 4 neutropenia occurred in 75% of patients. There was one treatment-related death. Dose reductions were required in 36% of patients. CONCLUSIONS: Docetaxel is active in paclitaxel-resistant ovarian and peritoneal cancer but, in view of significant hematologic toxicity, further study is warranted to ascertain its optimal dose and schedule.