Cigarette smoke promotes IL-6-dependent lung cancer migration and osteolytic bone metastasis.

Lung cancer stands as a major contributor to cancer-related fatalities globally, with cigarette smoke playing a pivotal role in its development and metastasis. Cigarette smoke is also recognized as a risk factor for bone loss disorders like osteoporosis. However, the association between cigarette smoke and another bone loss disorder, lung cancer osteolytic bone metastasis, remains largely uncertain. Our Gene Set Enrichment Analysis (GSEA) indicated that smokers among lung cancer patients exhibited higher expression levels of bone turnover gene sets. Both The Cancer Genome Atlas (TCGA) database and our clinic samples demonstrated elevated expression of the osteolytic factor IL-6 in ever-smokers with bone metastasis among lung cancer patients. Our cellular experiments revealed that benzo[α]pyrene (B[α]P) and cigarette smoke extract (CSE) promoted IL-6 production and cell migration in lung cancer. Activation of the PI3K, Akt, and NF-κB signaling pathways was involved in cigarette smoke-augmented IL-6-dependent migration. Additionally, cigarette smoke lung cancer-secreted IL-6 promoted osteoclast formation. Importantly, blocking IL-6 abolished cigarette smoke-facilitated lung cancer osteolytic bone metastasis in vivo. Our findings provide evidence that cigarette smoke is a risk factor for osteolytic bone metastasis. Thus, inhibiting IL-6 may be a valuable therapeutic strategy for managing osteolytic bone metastasis in lung cancer patients who smoke.

Characteristics and Related Factors of Bacterial Infection Among Patients With Cirrhosis.

Background: Infection causes cirrhosis to decompensate, affecting liver function and resulting in several complications, including esophageal variceal hemorrhage, hepatic encephalopathy, and hepatorenal syndrome. Objective: This study aimed to identify the prevalence, essential features, and related factors of bacterial infection among patients with cirrhosis in Vietnam. Methods: This retrospective study included 317 patients diagnosed with cirrhosis, who were divided into two groups: group 1 including 125 patients with bacterial infection and group 2 including 192 patients without bacterial infection. Infection was diagnosed on the basis of its localization. Results: Spontaneous bacterial peritonitis (SBP; 31.2%) and pneumonia (28.8%) were the most common infections identified. The procalcitonin (PCT) level had a strong diagnostic value with an area under the curve value of 0.868. The most common type of gram-negative bacteria was Escherichia coli, while the gram-positive bacteria seen were Staphylococcus, Enterococcus, and Streptococcus among the patients with infection. In the logistic regression analysis, Child-Pugh class B and C (p<0.001, OR=4.14, CI=1.90-9.03; OR=4.76, CI=2.03-11.16, respectively) and the presence of acute kidney injury (p=0.009, OR=2.57, CI=1.27-5.22) and gastrointestinal hemorrhage (p=0.035, OR=0.39, CI=0.16-0.94) significantly differed between the groups. Conclusion: The most prevalent type of bacterial infection in patients with cirrhosis is SBP, with gram-negative bacteria being the most common cause. The PCT level is useful in identifying infection in patients with cirrhosis. Decompensated cirrhosis is linked to a higher risk of infection.

Antrodia cinnamomea prevents ovariectomized-promoted bone loss by inhibiting osteoclast formation.

Osteoporosis is a common bone disease in aging populations, particularly in postmenopausal women. Anti-resorptive and anabolic drugs have been applied to prevent and cure osteoporosis and are linked with a variety of adverse effects. Antrodia cinnamomea extracts (ACE) are highly renowned for their anticancer, antioxidative, and anti-inflammatory properties. However, whether ACE-enriched anti-osteoporosis functions are largely unknown. In a preclinical animal model, we found that ovariectomy significantly decreased bone volume in the ovariectomized (OVX) rats. Administration of ACE antagonized OVX-induced bone loss. In addition, ACE reversed OVX-reduced biomechanical properties. The serum osteoclast marker also showed improvement in the ACE-treated group. In the cellular model, it was indicated that ACE inhibits RANKL-induced osteoclast formation. Taken together, ACE seems to be a hopeful candidate for the development of novel anti-osteoporosis treatment.

Bone sialoprotein promotes lung cancer osteolytic bone metastasis via MMP14-dependent mechanisms.

Bone metastases during lung cancer are common. Bone sialoprotein (BSP), a non-collagenous bone matrix protein, plays important functions in bone mineralization processes and in integrin-mediated cell-matrix interactions. Importantly, BSP induces bone metastasis in lung cancer, but the underlying mechanisms remain unclear. This study therefore sought to determine the intracellular signaling pathways responsible for BSP-induced migration and invasion of lung cancer cells to bone. Analyses of the Kaplan-Meier, TCGA, GEPIA and GENT2 databases revealed that high levels of BSP expression in lung tissue samples were associated with significantly decreased overall survival (hazard ratio = 1.17; p = 0.014) and with a more advanced clinical disease stage (F-value = 2.38, p < 0.05). We also observed that BSP-induced stimulation of matrix metalloproteinase (MMP)-14 promoted lung cancer cell migration and invasion via the PI3K/AKT/AP-1 signaling pathway. Notably, BSP promoted osteoclastogenesis in RAW 264.7 cells exposed to RANKL and BSP neutralizing antibody reduced osteoclast formation in conditioned medium (CM) from lung cancer cell lines. Finally, at 8 weeks after mice were injected with A549 cells or A549 BSP shRNA cells, the findings revealed that the knockdown of BSP expression significantly reduced metastasis to bone. These findings suggest that BSP signaling promotes lung bone metastasis via its direct downstream target gene MMP14, which reveals a novel potential therapeutic target for lung cancer bone metastases.

Integrated Medicine for Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of typical chemotherapeutics among cancer survivors. Despite the recent progress, the effective prevention and treatment strategies for CIPN remain limited. Better understanding of the pathogenesis of CIPN may provide new niches for developing a new ideal therapeutic strategy. This review summarizes the current understanding of CIPN and current recommendations along with completed/active clinical trials and aims to foster translational research to improve the development of effective strategies for managing CIPN.

Oophorectomy and tamoxifen adjuvant therapy in premenopausal Vietnamese and Chinese women with operable breast cancer.

PURPOSE: In 1992, the Early Breast Cancer Trialists' Collaborative Group reported that a meta-analysis of six randomized trials in European and North American women begun from 1948 to 1972 demonstrated disease-free and overall survival benefit from adjuvant ovarian ablation. Approximately 350,000 new cases of breast cancer are diagnosed annually in premenopausal Asian women who have lower levels of estrogen than western women. PATIENTS AND METHODS: From 1993 to 1999, we recruited 709 premenopausal women with operable breast cancer (652 from Vietnam, 47 from China) to a randomized clinical trial of adjuvant oophorectomy and tamoxifen (20 mg orally every day) for 5 years or observation and this combined hormonal treatment on recurrence. At later dates estrogen- and progesterone-receptor protein assays by immunohistochemistry were performed for 470 of the cases (66%). RESULTS: Treatment arms were well balanced. With a median follow-up of 3.6 years, there have been 84 events and 69 deaths in the adjuvant treatment group and 127 events and 91 deaths in the observation group, with 5-year disease-free survival rates of 75% and 58% (P =.0003 unadjusted; P =.0075 adjusted), and overall survival rates of 78% and 70% (P =.041 unadjusted) for the adjuvant and observation groups, respectively. Only patients with hormone receptor-positive tumors benefited from the adjuvant treatment. In Vietnam, for women unselected for hormone receptor status, a cost-effectiveness analysis suggests that this intervention costs $350 per year of life saved. CONCLUSION: Vietnamese and Chinese women with hormone receptor-positive operable breast cancer benefit from adjuvant treatment with surgical oophorectomy and tamoxifen.