Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement.

BACKGROUND & AIM: Several studies explored the association of vitamin B6 intake with the risk of cancers. However, it is unclear whether different doses of vitamin B6 have distinct effects on the prognosis of nasopharyngeal carcinoma (NPC) patients. This study investigated the relationship between different doses of B6 intake and the prognosis of NPC patients. METHODS: This retrospective cohort analysis included 792 newly diagnosed NPC patients with a median follow-up of 62.05 months. Restricted cubic spline and maximally selected rank statistics were performed to determine the cut-off value of vitamin B6 during treatment (VB6DT). Kaplan-Meier method and log-rank tests were performed to analyze survival outcomes. A multivariable Cox proportional hazard model was performed to determine the independent prognostic factors. RESULTS: NPC patients were divided into three groups according to the cut-off value of VB6DT: non-users (0 mg/d), VB6DT > 8.6 mg/d, and VB6DT ≤ 8.6 mg/d. Patients with VB6DT > 8.6 mg/d had significantly lower 5-year overall survival (OS) (83.5% vs. 90.8%, p = 0.006), distant metastasis-free survival (DMFS) (83.5% vs. 91.0%, p = 0.004), and progression-free survival (PFS) (73.7% vs. 81.7%, p = 0.011) and slightly but not significantly lower 5-year local recurrence-free survival (LRFS) (87.7% vs. 90.7%, p = 0.214) than the non-users. Patients with VB6DT ≤ 8.6 mg/d had slightly but not significantly better 5-year OS (93.3% vs. 90.8%, p = 0.283) than the non-users, while all other primary endpoints were similar (p > 0.50). Multivariable analyses confirmed that VB6DT > 8.6 mg/d was an independent negative prognostic factor of OS (p = 0.010), DMFS (p = 0.017), and PFS (p = 0.030) but not of LRFS (p = 0.428). CONCLUSIONS: Excessive VB6DT higher than the cut-off value is an independent negative prognostic factor for NPC patients. Additionally, low dose intake improved OS only slightly but not significantly.

Effects of Tai Chi Exercise on Cancer-Related Fatigue in Patients With Nasopharyngeal Carcinoma Undergoing Chemoradiotherapy: A Randomized Controlled Trial.

CONTEXT: Tai Chi exercise has been shown to improve cancer-related fatigue (CRF) and autonomic nervous system (ANS) balance in some cancer patients or survivors; however, such effects are yet to be verified in nasopharyngeal carcinoma (NPC) patients undergoing chemoradiotherapy. OBJECTIVES: To explore the effects of Tai Chi exercise on CRF in NPC patients undergoing chemoradiotherapy and then to evaluate ANS information indicated by heart rate variability parameters and their association with CRF. METHODS: A randomized controlled trial of Tai Chi exercise was conducted from January 2014 to August 2015. Participants in the Tai Chi group practiced Tai Chi a one-hour session, five sessions/week during chemoradiotherapy. Participants in the control group received usual care. The primary end points were scores of the multidimensional fatigue symptom inventory-short form (MFSI-SF). Secondary end points were heart rate variability parameters, including normalized low-frequency (nLF) power, normalized high-frequency (nHF) power, and the nLF/nHF ratio, and their association with CRF. RESULTS: One hundred fourteen patients were recruited in this study, and 83 patients completed the trial. The Tai Chi group and the control group had comparable baseline characteristics. After chemoradiotherapy, the Tai Chi group exhibited lower MFSI-SF total score and three negative subscale (general, physical, and emotional fatigue) scores and higher vigor score compared with the control group (P < 0.01 for all). The nLF/nHF ratio was significantly lower in the Tai Chi group compared to the control group after chemoradiotherapy. The MFSI-SF total score was markedly correlated with the nLF/nHF ratio. CONCLUSION: Tai Chi exercise is conducive to alleviate CRF in NPC patients undergoing chemoradiotherapy. The improvement in ANS balance might fit into the process of Tai Chi for CRF management in this population.

Morning breathing exercises prolong lifespan by improving hyperventilation in people living with respiratory cancer.

Disturbance of oxygen-carbon dioxide homeostasis has an impact on cancer. Little is known about the effect of breath training on cancer patients. Here we report our 10-year experience with morning breathing exercises (MBE) in peer-support programs for cancer survivors.We performed a cohort study to investigate long-term surviving patients with lung cancer (LC) and nasopharyngeal cancer (NPC) who practiced MBE on a daily basis. End-tidal breath holding time (ETBHT) after MBE was measured to reflect improvement in alveolar O2 pressure and alveolar CO2 pressure capacity.Patients (female, 57) with a diagnosis of LC (90 patients) and NPC (32 patients) were included. Seventy-six of them were MBE trainees. Average survival years were higher in MBE trainees (9.8 ±â€Š9.5) than nontrainees (3.3 ±â€Š2.8). The 5-year survival rate was 56.6% for MBE trainees and 19.6% for nontrainees (RR = 5.371, 95% CI = 2.271-12.636, P < 0.001). Survival probability of the trainees further increased 17.9-fold for the 10-year survival rate. Compared with the nontrainees, the MBE trainees shows no significant differences in ETBHT (baseline, P = 0.795; 1-2 years, P = 0.301; 3-4 years, P = 0.059) at baseline and within the first 4 years. From the 5th year onwards, significant improvements were observed in ETBHT, aCO2%, PaCO2, and PaO2 (P = 0.028). In total, 18 trainees (40.9%) and 20 nontrainees (74.1%) developed new metastasis (RR = 0.315, 95% CI = 0.108-0.919, P = 0.031).MBE might benefit for the long-term survival in patients with LC and NPC due to improvement in hyperventilation.

The effects of a 6-month Tai Chi Qigong training program on temporomandibular, cervical, and shoulder joint mobility and sleep problems in nasopharyngeal cancer survivors.

INTRODUCTION: Nasopharyngeal cancer (NPC) survivors often sustain head-neck-shoulder impairments from conventional treatments, which could disturb sleep. This novel study aimed to examine the efficacy of Tai Chi (TC) Qigong in optimizing temporomandibular joint (TMJ), cervical, and shoulder joint mobility and reducing sleep problems in NPC survivors. METHODS: Fifty-two NPC survivors participated in the study. The experimental group (n = 25) received 6 months of TC Qigong training (1.5 h/session; 4 sessions/wk including self-practice) while the control group (n = 27) received no training. Cervical side flexion and rotation, shoulder flexion and horizontal flexion range of motion (ROM), mouth opening capacity (interincisor distance), and sleep problems (Medical Outcomes Study Sleep Scale) were assessed at baseline, mid-intervention (3 months), immediately after TC Qigong training, and at 6-month follow-up. RESULTS: Intention-to-treat analysis revealed improvement in cervical side flexion ROM only (P < .008) and unchanged shoulder and TMJ mobility (P > .008) after the TC Qigong training. Deterioration was observed in shoulder flexion ROM and mouth opening capacity in the no-training controls over time (P < .008). Sleep problems also decreased in the TC Qigong group (P < .008), and this effect was most profound during the follow-up period. In addition, improvement in cervical side flexion ROM was associated with a reduction in sleep problems in the experimental group after TC Qigong training (P < .05). CONCLUSIONS: The 6-month TC Qigong intervention improved neck mobility, maintained TMJ and shoulder joint mobility, and reduced sleep problems for NPC survivors. TC Qigong could be an effective nonpharmacological intervention for managing progressive trismus, chronic neck and shoulder hypomobility, and reducing sleep problems among NPC survivors.

Six-year follow-up of a characteristic osteolytic lesion in a patient with tumor-induced osteomalacia.

OBJECTIVE: Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia and inappropriately normal or low 1,25-dihydroxyvitamin D. CLINICAL CASE: Here, we report a 6-year postoperative follow-up of a patient with oncogenic osteomalacia with a distinctive skeletal manifestation. The latter was characterized by an almost linear lytic lesion of a few millimeters with irregular borders, mainly involving the trabecular compartment but extending into cortical shell, located in the middle third of the right fibula. Six years after tumor resection, a sclerotic repair with a complete recovery was observed. Furthermore, we monitored a striking increase in bone mineral density throughout the observation period, reaching a peak of 73% over basal values at lumbar spine after 2 years; at total femur and radius, the peak was 47.5 and 4.6% respectively, after 4 years from tumor resection. CONCLUSIONS: We report for the first time that an osteolytic lesion may be part of the skeletal involvement in tumor-induced osteomalacia.

Reactive oxygen species-mediated mitochondrial dysfunction is involved in apoptosis in human nasopharyngeal carcinoma CNE cells induced by Selaginella doederleinii extract.

ETHNOPHARMACOLOGICAL RELEVANCE: A traditional Chinese medicine Selaginella doederleinii Hieron has been combined with radiotherapy for the treatment of human nasopharyngeal carcinoma in clinic in China. However, the detailed mechanism of anti-tumor effect of Selaginella doederleinii remains elusive. AIM OF THE STUDY: This study was designed to investigate the anti-tumor effect of ethanol extract of Selaginella doederleinii (SDE) on human nasopharyngeal carcinoma and its possible mechanisms. MATERIALS AND METHODS: Viability, apoptosis and protein expression of tumor cells were analyzed by MTT, Annexin V staining and Western blot, respectively. Formation of intracellular reactive oxygen species was determined using dichlorofluorescin fluorescence. The in vivo anti-tumor effect was evaluated by measuring tumor volume changes and TUNEL staining in nude mice. RESULTS: SDE significantly inhibited the growth and induced apoptosis in human nasopharyngeal carcinoma CNE cells. In addition, SDE triggered the mitochondrial/caspase apoptotic pathway indicated by enhanced Bax-to-Bcl-2 ratio, loss of mitochondrial membrane potential, cytochrome c release, and caspase cascade. Moreover, SDE provoked the generation of reactive oxygen species in CNE cells, while the antioxidant N-acetyl cysteine almost completely blocked SDE-induced disruption of mitochondrial membrane potential, caspases activation and apoptosis. Furthermore, a transplantable nude mice model was utilized to estimate the effectiveness of SDE in vivo. The treated mice displayed decreased tumor size, which was associated with enhanced apoptotic cell death. CONCLUSIONS: These results, offering solid evidence of the induction of mitochondria-related apoptosis in tumor cells, provide the molecular theoretical basis of clinical application of Selaginella doederleinii for the treatment of human nasopharyngeal carcinoma.

[Correlation of Ca2+ current features of nasopharyngeal carcinoma cells with different metastatic potentiality to their moving abilities].

BACKGROUND & OBJECTIVE: The metastatic potentiality of malignancies is closely associated with their biological dynamic properties, which are affected by intracellular Ca2+ current activity. This study was to investigate the correlation of Ca2+ current features of sub-clonal nasopharyngeal carcinoma (NPC) cell lines 5-8F and 6-10B with different metastatic potentiality to their moving abilities. METHODS: 5-8F cells, with higher metastatic potentiality, and 6-10B cells, with lower metastatic potentiality, were cultured with herbal medicine-containing serum, which holds significant metastasis-inhibiting effect on tumor cells. Cell proliferation was assessed by MTT assay. The expression of nm23-H1 was detected by Western blot. Intracellular Ca2+ current features were detected with patch clamp technique in a whole cell recording way, while cell moving ability was determined by streak culturing assay. RESULTS: The expression of nm23-H1 was significantly lower in 5-8F cells than in 6-10B cells (2.3+/-0.2 vs. 2.9+/-0.4). The Ca2+ release-activated Ca2+ influx current (ICRAC) was significantly lower in 5-8F cells than in 6-10B cells [(-1.39+/-0.36) nA vs. (-0.66+/-0.40) nA, P < 0.05]. The number of cells moved across the streak was significantly higher in 5-8F cells than in 6-10B cells (350+/-3 vs. 246+/-1, P< 0.05). When cultured with herbal medicine-containing serum, no significant difference in proliferation was found between 5-8F cells and 6-10B cells; the expression of nm23-H1 was significantly higher in 5-8F cells than in 6-10B cells(3.9+/-0.1 vs.1.0+/-0.1,P<0.05)û the ICRAC was decreased to (-1.27+/-0.35) nA in 5-8F cells and decreased to (-0.37+/-0.23) nA in 6-10B cell, and the inhibition rate was significantly higher in 5-8F cells than in 6-10B cells [(1.90+/-0.47)% vs. (0.46+/-0.12)%, P < 0.05]û the number of cells moved across the streak was significantly lower in 5-8F cells than in 6-10B cells (94+/-6 vs. 229+/-6, P < 0.05). CONCLUSIONS: There are significant differences in nm23-H1 protein expression, ICRAC level and cell moving ability between 5-8F and 6-10B cells. Medicine intervention could inhibit Ca2+ current and moving ability of 5-8F cells, and meanwhile increase the nm23-H1 activity.

Intracellular pH and heat sensitivity in two human cancer cell lines.

BACKGROUND AND PURPOSE: The majority of studies which have demonstrated a linear correlation between intracellular pH (pHi) and thermosensitivity have used rodent cell lines. In order to understand the therapeutic potential of this strategy, it is necessary to determine whether similar observations can be obtained with human cancer cells. MATERIALS AND METHODS: Human breast cancer MCF-7, and nasopharyngeal carcinoma CNE-1 cell lines were heated at 43 degrees C under extracellular pH (pHe) conditions of 7.2 or 6.8, +/- NaHCO3. We studied the function of the Na+/H+ antiport, one of the primary membrane regulators of pHi, pHi level, and clonogenic survival after these treatments. RESULTS: After 2-h exposure to 43 degrees C at pHe 7.2, antiport activity in MCF-7 cells was > 50% relative to that of unheated cells, in contrast to < 20% relative activity for CNE-1 cells. Respective survival levels under these conditions were 0.25 and 0.04. The addition of 5-(N-ethyl-N-isoproply) amiloride (EIPA), a potent inhibitor of Na+/H+ antiport, had no effect on MCF-7 cells, but enhanced cytotoxicity for CNE-1 cells, when heated at pHe 6.8 without NaHCO3. Analysis of the correlation between log surviving fraction and pHi demonstrated that this relationship was much steeper for CNE-1 compared to MCF-7 cells. CONCLUSION: The relationship between pHi levels and thermosensitivity observed in rodent cells can also apply to two human cancer cell lines: MCF-7 and CNE-1, with the latter cells being apparently more amenable to manipulations of pHi regulation compared to the former.