A new strategy for the treatment of heavily pretreated metastatic breast cancer: A case report and review of the literature.

BACKGROUND: Breast cancer is one of the most common type of cancers worldwide and remains a critical health issue. Although there are numerous treatment options for advanced metastatic breast cancer, the results are not satisfactory, particularly for triple-negative breast cancer. New treatment modalities need to be explored. CASE PRESENTATION: We present the case of a breast cancer patient with multiple metastases who achieved a good response and tolerance to the combination treatment of utidelone plus capecitabine. After being treated with 10 cycles of combined treatment, the patient is now in a good general condition with a progression-free survival time of 10 months. CONCLUSION: To our knowledge, this is the first report of utidelone plus capecitabine successfully treating a patient with heavily pretreated metastatic breast cancer. This combined treatment offers a new option for patients with multi-drug resistant breast cancer.

Role and mechanism of intraflagellar transport in mammalian spermiogenesis.

Eukaryotic cilia and flagella are evolutionarily conserved organelles that protrude from the cell surface. The unique location and properties of cilia allow them to function in vital processes such as motility and signaling. Ciliary assembly and maintenance rely on intraflagellar transport (IFT). Bidirectional movement of IFT particles composed of IFT-A and IFT-B complexes is powered by kinesin-2 and dynein-2 motors. IFT delivers building blocks between their site of synthesis in the cell body and the ciliary assembly site at the tip of the cilium. The integrity of the flagellum, a specialized organelle of mammalian sperm to generate the motility, is critical for normal sperm function. Recent findings suggest that IFT is indispensable for sperm flagellum formation and male fertility in mice and human. In this review, we summarize the role and mechanisms of IFT proteins during enflagellation in spermiogenesis, thereby discussing the pathological mechanisms of male infertility and providing theoretical basis for the diagnosis and treatment of male infertility.

UHRF1 gene silencing inhibits cell proliferation and promotes cell apoptosis in human cervical squamous cell carcinoma CaSki cells.

BACKGROUND: Up-regulation of UHRF1 has been observed in a variety of cancers and appears to serve as an independent prognostic factor. OBJECTIVE: To explore the effect of UHRF1 gene silencing on apoptosis and proliferation of cervical squamous cell carcinoma (CSCC) CaSki cells. METHODS: This study consisted of 47 CSCC tissues and 40 normal cervical tissues. The CaSki cells were assigned into Blank group (CaSki cells not transfected), NC group (CaSki cells transfected with control siRNA), and UHRF1 Silence group (CaSki cells transfected with UHRF1 siRNA). qRT-PCR and Western blot were used for UHRF1 mRNA and protein expressions, CKK-8 assay for cell proliferation, flow cytometry for cell cycle and apoptosis, Western blot for expressions of apoptosis-related proteins. Nude mice tumor transplant experiment was performed. RESULTS: UHRF1 exhibited higher mRNA and protein expressions in the CSCC tissues than normal cervical tissues (both P < 0.05). The cell proliferation ability in the UHRF1 Silence group was reduced when compared with the Blank group and the NC group, the cells at S-G2M stage in the UHRF1 Silence group were dropped when compared with the Blank group and the NC group (P < 0.05), while the cells at G0/G1 stage were elevated (P < 0.05), and the proportion of Annexin V positive cells in the UHRF1 Silence group was increased in comparison with the Blank group and the NC group (P < 0.05). Nude mice tumor transplant experiment indicated that the growth rate and weight of tumor in the Blank group and NC group was higher and heavier than the UHRF1 Silence group (P < 0.05). CONCLUSION: UHRF1 showed a high expression in CSCC and UHRF1 silencing can reduce proliferation and enhance apoptosis of the CaSki cells.

Ubiquitin-specific protease 22: a novel molecular biomarker in cervical cancer prognosis and therapeutics.

Ubiquitin-specific protease 22 (USP22) exhibits an important function in tumor progression and oncogenesis. The aim of this study was to investigate the role of USP22 and the association with its potential targets in patients with cervical cancer. To our knowledge, this is the first study that determines the relationship between USP22 expression and clinicopathological significance in cervical cancer. The immunohistochemistry results showed that USP22 protein was overexpressed in cervical cancer samples compared with normal cervical tissues (P < 0.001). Moreover, clinicopathological analysis showed that USP22 expression was highly related to International Federation of Gynecology and Obstetrics stage, Ki67, lymph node metastasis, and histology grade. The results of Kaplan-Meier analysis indicated that patients with high USP22 expression had significantly shorter overall survival (OS) and disease-free survival (DFS) than patients with low expression of USP22 (P < 0.001). Multivariate Cox regression analysis revealed that USP22 expression status was an independent prognostic marker for both OS and DFS of patients with cervical cancer. It is suggested that USP22 overexpression may be associated with poor prognosis in cervical cancer. It may represent a novel prognostic biomarker or a target for improving the treatment efficiency of patients with cervical cancer.

Strengthening and optimal movements for painful shoulders (STOMPS) in chronic spinal cord injury: a randomized controlled trial.

BACKGROUND: Shoulder pain is a common problem after spinal cord injury (SCI), with negative effects on daily activities and quality of life (QOL). OBJECTIVE: The purpose of this study was to determine the effect of an exercise program and instruction to optimize performance of upper-extremity tasks on shoulder pain in people with paraplegia from SCI. METHODS: Design Eighty individuals with paraplegia from SCI and shoulder pain were randomly assigned to receive either an exercise/movement optimization intervention or an attention control intervention. The exercise/movement optimization intervention consisted of a 12-week home-based program of shoulder strengthening and stretching exercises, along with recommendations on how to optimize the movement technique of transfers, raises, and wheelchair propulsion. The attention control group viewed a 1-hour educational video. Outcome measures of shoulder pain, muscle strength (force-generating capacity), activity, and QOL were assessed at baseline, immediately after intervention, and 4 weeks later. RESULTS: Shoulder pain, as measured with the Wheelchair User's Shoulder Pain Index, decreased to one third of baseline levels after the intervention in the exercise/movement optimization group, but remained unchanged in the attention control group. Shoulder torques, most 36-Item Short-Form Health Survey questionnaire (SF-36) subscale scores, and QOL scores also were improved in the exercise/movement optimization group, but not in the attention control group. Improvements were maintained at the 4-week follow-up assessment. Limitations Many of the outcome measures were self-reported, and the participant dropout rate was high in both groups. Additional studies are needed to determine whether the results of this study can be generalized to individuals with tetraplegia. CONCLUSIONS: This home-based intervention was effective in reducing long-standing shoulder pain in people with SCI. The reduction in pain was associated with improvements in muscle strength and health-related and overall QOL.

An intensive, progressive exercise program reduces disability and improves functional performance in patients after single-level lumbar microdiskectomy.

BACKGROUND: Restoration of physical function following lumbar microdiskectomy may be influenced by the postoperative care provided. OBJECTIVE: The purpose of this study was to examine the effectiveness of a new interventional protocol to improve functional performance in patients who have undergone a single-level lumbar microdiskectomy. SETTING: The study was conducted in physical therapy outpatient clinics. DESIGN AND PARTICIPANTS: Ninety-eight participants (53 male, 45 female) who had undergone a single-level lumbar microdiskectomy were randomly allocated to receive education only or exercise and education. INTERVENTION AND MEASUREMENTS: The exercise intervention consisted of a 12-week periodized program of back extensor strength (force-generating capacity) and endurance training and mat and upright therapeutic exercises. The Oswestry Disability Index (ODI) and physical measures of functional performance were tested 4 to 6 weeks postsurgery and 12 weeks later, following completion of the intervention program. Because some participants sought physical therapy outside of the study, postintervention scores were analyzed for both an as-randomized (2-group) design and an as-treated (3-group) design. RESULTS: In the 2-group analyses, exercise and education resulted in a greater reduction in ODI scores and a greater improvement in distance walked. In the 3-group analyses, post hoc comparisons showed a significantly greater reduction in ODI scores following exercise and education compared with the education-only and usual physical therapy groups. LIMITATIONS: The limitations of this study include a lack of adherence to group assignment, disproportionate therapist contact time among treatment groups, and multiple use of univariate analyses. CONCLUSIONS: An intensive, progressive exercise program combined with education reduces disability and improves function in patients who have undergone a single-level lumbar microdiskectomy.