Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer.

Currently, the survival rate for breast cancer is more than 90%, but once the cancer cells metastasize to distal organs, the survival rate is dramatically reduced, to less than 30%. Triple-negative breast cancer accounts for 15-20% of all breast cancers. Triple-negative breast cancer (TNBC) is associated with poor prognostic and diagnostic outcomes due to the limiting therapeutic strategies, relative to non-TNBC breast cancers. Therefore, the development of targeted therapy for TNBC metastasis remains an urgent issue. In this study, high Carboxyl-terminal modulator protein (CTMP) is significantly associated with recurrence and disease-free survival rate in TNBC patients. Overexpression of CTMP promotes migration and invasion abilities in BT549 cells. Down-regulating of CTMP expression inhibits migration and invasion abilities in MDA-MB-231 cells. In vivo inoculation of high-CTMP cells enhances distant metastasis in mice. The metastasis incidence rate is decreased in mice injected with CTMP-downregulating MDA-MB-231 cells. Gene expression microarray analysis indicates the Akt-dependent pathway is significantly enhanced in CTMP overexpressing cells compared to the parental cells. Blocking Akt activation via Akt inhibitor treatment or co-expression of the dominant-negative form of Akt proteins successfully abolishes the CTMP mediating invasion in TNBC cells. Our findings suggest that CTMP is a potential diagnostic marker for recurrence and poor disease-free survival in TNBC patients. CTMP promotes TNBC metastasis via the Akt-activation-dependent pathway.

Potential benefits of palliative care for polysymptomatic patients with late-stage nonmalignant disease in Taiwan.

BACKGROUND/PURPOSE: Taiwan is only now beginning to offer palliative care to patients who do not have cancer. This study aimed to document the polysymptomatic presentation of illness in Taiwanese patients with late-stage nonmalignant disease and to evaluate the potential benefits of palliative care for these patients. The results may help to educate healthcare personnel regarding the need for and importance of palliative treatment as comprehensive, appropriate end-of-life care for patients with nonmalignant disease. METHODS: We retrospectively analyzed 115 patients without cancer hospitalized in a community hospital in Taiwan: 61 had organic brain disease, 31 had chronic obstructive pulmonary disease, 17 had chronic renal failure, 14 had congestive heart failure, 12 had liver cirrhosis, and 20 had multiple illnesses. The median age was 81 years (interquartile range 69-86 years), and 51% of patients were enrolled from intensive care. Symptoms and their severity were analyzed. Patients' and their families' understanding of the diagnosis and prognosis and "Do Not Resuscitate" (DNR) consent were evaluated pre- and post-palliative care. RESULTS: The four leading symptoms were fatigue (96%), fever (86%), cough (81%), and dyspnea (79%). No significant differences in symptom prevalence were found between different sexes, ages, performance statuses, ward locations, or underlying diseases, except for fewer episodes of dizziness, more frequent episodes of cough in patients older than 80 years, and more episodes of jaundice in ward service subjects. Only the presence of abdominal distension differed significantly between surviving and deceased patients (22.9% vs. 40.3%; p=0.004). After the start of palliative care, patients' DNR consent increased (105/115 before, 114/115 after). Patients' recognition of the diagnosis and prognosis increased from 13 to 64, respectively, with a simultaneous increase in family members' recognition (66 before, 114 after). CONCLUSION: Hospice care with good symptom control is warranted for patients with late-stage nonmalignant disease who need appropriate end-of-life care. Medical personnel need education in the importance of palliative care and the identification of patients who could benefit from it. In addition, patients should be informed of its availability.

Comparing end-of-life care for hospitalized patients with chronic obstructive pulmonary disease and lung cancer in Taiwan.

When it comes to end-of-life care, chronic obstructive pulmonary disease (COPD) patients are often treated differently from lung cancer patients. However, few reports have compared end-of-life care between these two groups. We investigated the differences between patients with end-stage COPD and end-stage lung cancer based on end-of-life symptoms and clinical practice patterns using a retrospective study of COPD and lung cancer patients who died in an acute care hospital in Taiwan. End-stage COPD patients had more comorbidities and spent more days in the intensive care unit (ICU) than end-stage lung cancer patients. They were more likely to die in the ICU and less likely to receive hospice care. COPD patients also had more invasive procedures, were less likely to use narcotic and sedative drugs, and were less likely to have given do-not-resuscitate consent. Symptoms were similar between these two groups. Differences in treatment management suggest that COPD patients receive more care aimed at prolonging life than care aimed at relieving symptoms and providing end-of-life support. It may be more difficult to determine when COPD patients are at the end-of-life stage than it is to identify when lung cancer patients are at that stage. Our findings indicate that in Taiwan, more effort should be made to give end-stage COPD patients the same access to hospice care as end-stage lung cancer patients.

Effect of hyaluronic acid on urine nerve growth factor in cyclophosphamide-induced cystitis.

OBJECTIVES: To investigate how hyaluronic acid (HA) affects nerve growth factor (NGF) production and bladder overactivity in a cyclophosphamide (CYP)-induced cystitis rat model. METHODS: Female Sprague-Dawley rats received three intermittent intraperitoneal injections of CYP (75 mg/kg) or saline. Before or after CYP injection, HA was given intravesically and urine NGF was checked with creatinine correction. Bladder function was evaluated by cystometrograms under Zoletil anesthesia. Furthermore, the effect of HA was counteracted with hyaluronidase (HYAL). Bladder structural change was compared among groups with trichrome stain. RESULTS: The intercontraction interval (ICI) significantly decreased in CYP-injected rats in comparison to the saline-injected controls. In the CYP-injected groups, bladder HA instillation significantly increased the ICI, but did not change the maximum voiding pressure in comparison to the saline instillation. NGF production significantly increased in CYP-injected rats, but decreased significantly with HA treatment. Treatment with HA had a more significant effect on urine NGF and the use of HYAL would eliminate this effect. Specific staining showed mucosa swelling after CYP treatment. Little HA coating on bladder mucosa could be found in HA-treated rats. CONCLUSIONS: Present findings raise the possibility that HA could be an effective treatment for CYP-related bladder overactivity through the involvement of NGF signaling.