Inhibiting the Musculoskeletal Pathological Processes in Post-knee Replacement Surgery With Osteopathic Manipulative Treatment: A Systematic Review.

Total knee arthroplasty (TKA) is a very common surgical treatment approach for severe osteoarthritis. Complications of TKA include loss of range of motion and prolonged analgesic requirement for pain control. Osteopathic manipulative techniques (OMT) have been utilized to address localized muscular stiffness to improve range of motion; however, limited studies directly correlate OMT and TKA recovery. This review highlights the therapeutic benefits OMT can have in the postoperative management of arthroplasty with respect to range of motion, edema, pain perception, and ability to perform activities of daily living. This review revealed the use of OMT would positively influence range of motion by manipulation of localized musculature and can result in decreased demand for analgesics. This can, in turn, shorten hospital stay and return the ability of patients to perform activities of daily living earlier than without OMT. Increased research is needed to strengthen these findings on the benefits of OMT in the postoperative management of arthroplasty.

Palliative Medicine in Myelodysplastic Syndromes: Patients and Caregivers - A Qualitative Study.

OBJECTIVES: Evidence-based guidelines call for integration of palliative care within oncology from diagnosis. Misperceptions about palliative care have impeded implementation. Prior research has not examined perceptions about 'palliative care' versus 'supportive care' among patients and caregivers to whom this care is introduced routinely as part of comprehensive cancer care. We conducted a qualitative study of patients with myelodysplastic syndromes (MDS) and their informal caregivers to elicit perceptions of 'palliative care' and 'supportive care' before and after they received integrated primary/specialist palliative care from diagnosis. METHODS: Patients with newly diagnosed MDS and caregivers were interviewed about their understanding of 'palliative care' and 'supportive care' at diagnosis and follow-up. Interviews were audio-recorded, transcribed, and analysed by an interdisciplinary team. RESULTS: Forty-eight interviews were conducted in total, including with 21 patients and 13 caregivers at diagnosis, and 10 patients and 4 caregivers at follow-up. Initially, 28/34 participants (82%) associated 'palliative care' with death or fear/alarm. At follow-up, 11/14 participants (79%) recognised that 'palliative care' is not only for terminally ill patients, yet 13/14 participants (93%) still felt apprehensive about the term. Initially, 24/34 participants (71%) felt 'supportive care' sounded 'positive' and 12/14 participants (86%) reported this at follow-up. No participant associated 'supportive care' with death or fear/alarm at either time point. Among participants who had a preference, 'supportive care' was the preferred term initially and at follow-up. CONCLUSIONS: Patients with MDS and caregivers receiving integrated primary/specialist palliative care from diagnosis responded more favourably to and felt less apprehensive about 'supportive care', initially and at follow-up.

(-)-Gossypol reduces invasiveness in metastatic prostate cancer cells.

BACKGROUND: Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. (-)-Gossypol, a polyphenolic compound present in cottonseeds, possesses anti-proliferative and proapoptotic effects in various cancer cells. MATERIALS AND METHODS: In this study, the differences between MAT-LyLu, rat prostate cancer cells, with a novel isolated subline from metastasized tumors in the lungs of MAT-LyLu-bearing Copenhagen rats (MLL cells) were compared with respect to cell growth and invasion. The effects of (-)-gossypol on cell viability, colony formation, invasive ability and cell migration in MAT-LyLu and MLL cells were also evaluated. RESULTS: Results showed that MLL cells displayed higher growth ability, colony formation and aggressive penetration than those of MAT-LyLu cells. MLL cells possess lower protein expression of Bcl-xL and nm23-H1 than those of MAT-LyLu cells, implying differences in invasive ability. Moreover, (-)-gossypol treatment induced a dose-dependent inhibition of invasive activity and cell viability and reduced Bcl-2 and Bcl-xL proteins but induced nm23-H1 protein in both cell lines. CONCLUSION: These findings illustrated that (-)-gossypol reduced in vitro invasion of both the parental MAT-LyLu cells and the isolated MLL cells, suggesting that (-)-gossypol might serve as a chemotherapeutic and/or chemopreventive agent.

Giving Voice to Patient Values Throughout Cancer: A Novel Nurse-Led Intervention.

CONTEXT: Optimal advance care planning allows patients to articulate their values as a touchstone for medical decision making. Ideally, this occurs when patients are clinically stable, and with opportunities for iteration as the clinical situation unfolds. OBJECTIVES: Testing feasibility and acceptability in busy outpatient oncology clinics of a novel program of systematic, oncology nurse-led values discussions with all new cancer patients. METHODS: Within an institutional initiative integrating primary and specialist palliative care from diagnosis for all cancer patients, oncology nurses were trained to use specific questions and an empathic communication framework to discuss health-related values during outpatient clinic visits. Nurses summarized discussions on a template for patient verification, oncologist review, and electronic medical record documentation. Summaries were reviewed with the patient at least quarterly. Feasibility and acceptability were evaluated in three clinics for patients with hematologic or gastrointestinal malignancies. RESULTS: Oncology nurses conducted 177 total discussions with 67 newly diagnosed cancer patients (17 with hematologic and 50 with gastrointestinal malignancies) over two years. No patient declined participation. Discussions averaged eight minutes, and all patients verified values summaries. Clinic patient volume was maintained. Of 31 patients surveyed, 30 (97%) reported feeling comfortable with the process, considered it helpful, and would recommend it to others. Clinicians strongly endorsed the values discussion process. CONCLUSION: Nurse-led discussions of patient values soon after diagnosis are feasible and acceptable in busy oncology clinics. Further research will evaluate the impact of this novel approach on additional patient-oriented outcomes after broader dissemination of this initiative throughout our institution.

Modulation of multidrug resistance gene expression in human breast cancer cells by (-)-gossypol-enriched cottonseed oil.

BACKGROUND: Multidrug resistance (MDR) is a major impediment to successful cancer chemotherapy. P-glycoprotein (P-gp), the product of the multidrug resistance 1 (MDR1) gene, acts as an efflux pump and prevents sufficient intracellular accumulation of several anticancer agents, thus, playing a major role in MDR. Tamoxifen (Tam), ICI 182 780 (ICI) and Adriamycin (Adr) alone or with (-)-gossypol-enriched cottonseed oil [(-)-GPCSO] possible effects on cell growth inhibition and regulation of MDR1, mRNA and P-gp expression were examined in both an MDR human breast cancer cell line, MCF-7/Adr cells, and primary cultured human breast cancer epithelial cells (PCHBCEC). MATERIALS AND METHODS: Cells were treated with 0.05% of (-)-GPCSO either in the absence or presence of either 0.1 microM Tam, ICI or Adr for 24 h. RESULTS: Using the non-radioactive cell proliferation MTS assay, none of these chemotherapeutic agents alone inhibited MCF-7/Adr cell and PCHBCEC proliferation; meanwhile, the combination of 0.1 microM Tam, ICI or Adr with 0.05% (-)-GPCSO significantly reduced MCF-7/Adr cell growth by approximately 34%, 32% and 23%, respectively, of that of the vehicle-treated cells. For PCHBCEC, the combination of 0.05% (-)-GPCSO with 0.1 microM of Tam, ICI and Adr reduced cell growth to about 94%, 90%, and 71% respectively, of the vehicle treated PCHBCEC. Furthermore, (-)-GPCSO inhibited MDR1/P-gp expression in both MCF- 7/Adr and PCHBCEC in a dose-dependent manner. Our results provide insight into the MDR-reversing potential of (-)-GPCSO in human breast cancer cells resistant to current chemotherapeutic agents.

Effects of serum on (-)-gossypol-suppressed growth in human prostate cancer cells.

BACKGROUND: Gossypol, a natural polyphenolic compound present in cottonseeds, possesses antiproliferative and pro-apoptotic effects in in vivo and in vitro models. There are two enantiomers, (+)-gossypol and (-)-gossypol, the latter being a more potent inhibitor of cancer cell growth. Here, the effect of bovine serum albumin (BSA) and dextran-coated charcoal-treated fetal bovine serum (DCC-FBS)-containing medium on the ability of (-)-gossypol to inhibit the growth of human prostate cancer cells was studied. MATERIALS AND METHODS: BSA- and DCC-FBS-supplemented medium were used to examine the influence of serum proteins on the antiproliferative effects of (-)-gossypol in DU-145 cells, a human prostate cancer cell line. The viability of the DU-145 cells was determined by CellTiter 96 Aqueous assay. The expressions of mRNA and protein for the cell cycle regulators, cyclin-D1, Rb, CDK, p21 and TGF-beta, were determined by RT-PCR and Western blot analyses, respectively. RESULTS: (-)-Gossypol caused growth suppression of the DU-145 cells. In comparison with BSA-supplemented medium, DCC-FBS blocked the antiproliferative effects of (-)-gossypol at 1 and 2.5 microM, but not at 5 microM. Furthermore, (-)-gossypol treatment down-regulated cyclin-D1, Rb, CDK4 and CDK6, and up-regulated p21 and TGF-beta1 at the mRNA and/or protein levels. CONCLUSION: The data suggested that (-)-gossypol-suppressed prostate cancer cell growth may be influenced through cell cycle regulators, which may lead to better prognosis. We further speculate that (-)-gossypol might serve as a chemotherapeutic agent for human prostate cancer patients.

Molecular mechanisms of (-)-gossypol-induced apoptosis in human prostate cancer cells.

BACKGROUND: Gossypol, a natural compound present in cottonseeds, displays antiproliferative and pro-apoptotic effects against various cancer cells. The (-)-gossypol enantiomer is a more potent inhibitor of cancer cell growth. Here, the molecular mechanisms of apoptosis induced by (-)-gossypol were studied in human prostate cancer cells. MATERIALS AND METHODS: After the prostate cancer cell DU-145 had been treated with (-)-gossypol, the trypan blue exclusion assay and DNA fragment end-labeling assay were used to stain the dead cells and to detect DNA laddering, respectively. The effects of (-)-gossypol on the expression of apoptotic-regulated gene markers in both death receptor- and mitochondria-mediated apoptotic pathways, such as the Bcl-2 family and caspase, etc., were detected by RT-PCR and Western blot analysis. To further investigate the apoptotic pathways induced by (-)-gossypol, different caspase inhibitors were used to block caspase activities and cell viability was detected by the CellTiter 96 AQueous assay in DU-145 cells. RESULTS: At a 5-10 microM dose-level, (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation. (-)-Gossypol caused apoptosis in DU-145 cells through the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax at the mRNA and protein levels. (-)-Gossypol also activated caspases-3, -8 and -9 and increased PARP [poly (ADP-ribose) polymerase] cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase in CAD (caspase-activated deoxyribonuclease) proteins and a decrease in ICAD (inhibitor of CAD) proteins. By using caspase inhibitors, (-)-gossypol caused apoptosis via the caspase-dependent pathways. CONCLUSION: Our results indicated that the apoptotic processes caused by (-)-gossypol are mediated by the regulation of the Bcl-2 and caspase families in human prostate cancer cells. Our data also suggested that (-)-gossypol may have chemotheraputic benefits for prostate cancer patients.

Development of competitive direct ELISA for gossypol analysis.

Anti-gossypol monoclonal antibody was purified from cell culturing supernatant by ammonium sulfate precipitation and Protein A AffinityPak. The antigen (i.e., gossypol) was labeled with horseradish peroxidase through Schiff-base formation. Both the purified antibody and the enzyme-labeled gossypol were employed to develop a competitive direct enzyme-linked immunosorbent assay (cdELISA) for gossypol analysis. I50 value, the concentration of gossypol causing 50% inhibition of the maximum ELISA signal in the competitive standard curve, was 0.067 microg/mL, whereas the detection limit for gossypol was 0.005 microg/mL. We also observed a good correlation (R2= 0.96, P < 0.05) between the cdELISA method and the AOCS official method for "free" gossypol (extractable gossypol and gossypol derivatives by 70% acetone) analysis of cottonseed meals. This indicates that the newly developed cdELISA could be a valuable and feasible alternative for determination of "free" gossypol, especially when the available sample is limited with relatively low gossypol concentration.

Development of monoclonal antibody-based enzyme-linked immunosorbent assay for gossypol analysis in cottonseed meals.

A monoclonal antibody-based indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was developed for the analysis of gossypol in cottonseed meals. First, the checkerboard method was used to determine the optimum amount of coating antigen gossypol-BSA (bovine serum albumin) and primary anti-gossypol monoclonal antibody (Mab) needed in the ic-ELISA. Second, the effects of several physical (incubation time and temperature) and chemical (solvent types and concentrations) conditions on the performance of Mab on ic-ELISA were investigated to get a rapid robust assay with high sensitivity. Under the established optimized condition, the concentration of gossypol giving 50% reduction of the maximum ELISA signal (I50) in the competitive standard curve was 0.20 microg/mL, whereas the detection limit for gossypol was 0.024 microg/mL. This ic-ELISA method for the analysis of gossypol extracted by methanol from a variety of cottonseed meals was further compared with the official method of the American Oil Chemists' Society (AOCS). The amounts of gossypol determined by the ic-ELISA had a good correlation with those obtained by the AOCS method (R2 = 0.90).

Induction of apoptosis by (-)-gossypol-enriched cottonseed oil in human breast cancer cells.

Induction of apoptosis is one of the mechanisms of chemotherapeutic agents against breast cancer. In addition, recent studies have shown that diets containing polyphenolic components possess anticancer activities either in vitro or in vivo by inhibiting cell proliferation and inducing apoptosis. The aim of our study was to explore the effects of (-)-gossypol-enriched cottonseed oil [(-)-GPCSO], a polyphenolic compound, on the proliferation of the breast cancer cell line MCF-7 as well as primary cultured human breast cancer epithelial cells (PCHBCEC). We investigated whether the mechanism of the effects of (-)-GPCSO was mediated via the induction of cell apoptosis and the regulation of Bcl-2 gene expression at both the mRNA and protein levels. Our results showed that (-)-GPCSO inhibited the proliferation of MCF-7 and PCHBCEC in a dose-dependent manner. (-)-GPCSO (0.1 and 0.2%) induced DNA fragmentation in both MCF-7 cells and PCHBCEC. (-)-GPCSO suppressed the expression of Bcl-2 at both the mRNA and protein levels in MCF-7 cells and PCHBCEC in a dose-dependent fashion. Our results suggest that the growth inhibitory effect of (-)-GPCSO on MCF-7 and PCHBCEC is due, at least partially, to the induction of cell apoptosis, which is mediated by down-regulation of Bcl-2 expression at both the mRNA and protein levels. It might be possible for (-)-GPCSO to be developed as a novel chemotherapeutic agent for breast cancer patients.