Circulating Tumor Cells Enumerated by a Centrifugal Microfluidic Device as a Predictive Marker for Monitoring Ovarian Cancer Treatment: A Pilot Study

We investigated the size-based isolation and enumeration of circulating tumor cells (CTCs) using a centrifugal microfluidic device equipped with a fluid-assisted separation technology (FAST) disc. We further assessed the correlations among CTCs, cancer antigen-125 (CA125) levels, and clinical course of the disease in a prospective analysis of 47 serial blood samples collected at multiple time-points from 13 ovarian cancer patients. CTCs were isolated from whole blood using the FAST disc and were classified as epithelial cell adhesion molecule (EpCAM)/cytokeratin+, CD45-, and 4 ',6-diamidino-2-phenylindole (DAPI)+. Mean CTC count at baseline was 20.2; 84.62% of patients had more than one CTC at baseline and had decreased CTCs counts after surgery and chemotherapy. The CTC counts in eight patients with complete responses were <3. CTC counts were correlated with CA125 levels in three patients without recurrence; they were elevated in three patients with recurrence and normal CA125 concentrations. CTC counts and CA125 levels showed high concordance with directional changes (increasing 71.4%; non-increasing 75.0%). CTC counts showed higher associations with clinical status, sensitivity (100.0% vs. 60.0%), positive predictive value (55.6% vs. 42.9%), and negative predictive value (100.0% vs. 87.5%) than CA125 levels. CTC counts were better associated with treatment response and recurrence than CA125 levels

Cyclin-Dependent Kinase Inhibitor p27Kip1 Controls Growth and Cell Cycle Progression in Human Uterine Leiomyoma

The molecular mechanism of the cell-cycle machinery in uterine leiomyoma has not yet been fully elucidated. Among the various types of cell-cycle regulators, p27Kip1 (p27) is considered to be a potent tumor suppressor. To provide further molecular basis for understanding the progression of uterine leiomyoma, our objective was to evaluate the expression level of p27 in normal myometrium and uterine leiomyoma tissue and its effect on cytogenic growth. Western blot analysis, real-time polymerase chain reaction (PCR) and immunohistochemical staining revealed that p27 protein and messenger RNA were down-regulated in uterine leiomyoma tissue and cultured cells compared to normal myometerium. Full-length human p27 cDNA was transferred using a replication-deficient recombinant adenoviral vector (Ad.p27) into uterine leiomyoma cells and evaluated the effect on cell proliferation. Transfection of Ad.p27 into uterine leiomyoma cells resulted in the induction of apoptosis, reduction in viability and proliferation of uterine leiomyoma cells. Our results suggest a new paradigm that down-regulated p27 protein expression is the possible underlying mechanism for the growth of uterine leiomyoma and over-expression of p27 induces cell death. This study provides better understanding of the control exerted by p27 in regulating growth and disease progression of uterine leiomyoma

A randomized controlled trial of physical activity, dietary habit, and distress management with the Leadership and Coaching for Health (LEACH) program for disease-free cancer survivors

Background We aimed to evaluate the potential benefits of the Leadership and Coaching for Health (LEACH) program on physical activity (PA), dietary habits, and distress management in cancer survivors. Methods We randomly assigned 248 cancer survivors with an allocation ratio of two-to-one to the LEACH program (LP) group, coached by long-term survivors, or the usual care (UC) group. At baseline, 3, 6, and 12 months, we used PA scores, the intake of vegetables and fruits (VF), and the Post Traumatic Growth Inventory (PTGI) as primary outcomes and, for secondary outcomes, the Ten Rules for Highly Effective Health Behavior adhered to and quality of life (QOL), the Hospital Anxiety and Depression Scale (HADS), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Results For primary outcomes, the two groups did not significantly differ in PA scores or VF intake but differed marginally in PTGI. For secondary outcomes, the LP group showed a significantly greater improvement in the HADS anxiety score, the social functioning score, and the appetite loss and financial difficulties scores of the EORTC QLQ-C30 scales from baseline to 3 months. From baseline to 12 months, the LP group showed a significantly greater decrease in the EORTC QLQ-C30 fatigue score and a significantly greater increase in the number of the Ten Rules for Highly Effective Health Behavior. Conclusion Our findings indicate that the LEACH program, coached by long-term survivors, can provide effective management of the QOL of cancer survivors but not of their PA or dietary habits. Trial registration Clinical trial information can be found for the following: NCT01527409 (the date when the trial was registered: February 2012)

In vivo modeling of metastatic human high-grade serous ovarian cancer in mice

Metastasis is responsible for 90% of human cancer mortality, yet it remains a challenge to model human cancer metastasis in vivo. Here we describe mouse models of high-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), the most common and deadliest human ovarian cancer type. Mice genetically engineered to harbor Dicer1 and Pten inactivation and mutant p53 robustly replicate the peritoneal metastases of human HGSC with complete penetrance. Arising from the fallopian tube, tumors spread to the ovary and metastasize throughout the pelvic and peritoneal cavities, invariably inducing hemorrhagic ascites. Widespread and abundant peritoneal metastases ultimately cause mouse deaths (100%). Besides the phenotypic and histopathological similarities, mouse HGSCs also display marked chromosomal instability, impaired DNA repair, and chemosensitivity. Faithfully recapitulating the clinical metastases as well as molecular and genomic features of human HGSC, this murine model will be valuable for elucidating the mechanisms underlying the development and progression of metastatic ovarian cancer and also for evaluating potential therapies

A case of an endobronchial metastasis from an endometrial carcinoma

A 73-year-old woman was referred to the pulmonology department for abnormal findings on chest computed tomography. She had undergone a laparoscopic staging operation including a hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic node and para-aortic node dissection, and concurrent chemo-radiation therapy for endometrial serous carcinoma stage IIIc cancer 15 months earlier. A follow-up chest computed tomography after the chemotherapy showed that the right lower lobe bronchus was obstructed, and it was necessary to differentiate a primary lung malignancy from a metastasis and secretion. A positron emission tomography revealed an intense hypermetabolic nodule in the right lower lobe bronchus and diffuse hypometabolism of the right lower lobe lung. Bronchoscopy revealed a tumor mass obstructing the right lower lobe bronchus, and an endobronchial biopsy confirmed a metastatic serous carcinoma from the endometrium. We described an endobronchial metastasis from an endometrial carcinoma with various diagnostic images and histology. To the best of our knowledge, this is the first report of an endobronchial metastasis from an endometrial carcinoma in Korea

A case of an endobronchial metastasis from an endometrial carcinoma

A 73-year-old woman was referred to the pulmonology department for abnormal findings on chest computed tomography. She had undergone a laparoscopic staging operation including a hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic node and para-aortic node dissection, and concurrent chemo-radiation therapy for endometrial serous carcinoma stage IIIc cancer 15 months earlier. A follow-up chest computed tomography after the chemotherapy showed that the right lower lobe bronchus was obstructed, and it was necessary to differentiate a primary lung malignancy from a metastasis and secretion. A positron emission tomography revealed an intense hypermetabolic nodule in the right lower lobe bronchus and diffuse hypometabolism of the right lower lobe lung. Bronchoscopy revealed a tumor mass obstructing the right lower lobe bronchus, and an endobronchial biopsy confirmed a metastatic serous carcinoma from the endometrium. We described an endobronchial metastasis from an endometrial carcinoma with various diagnostic images and histology. To the best of our knowledge, this is the first report of an endobronchial metastasis from an endometrial carcinoma in Korea