To investigate the changes in bone metabolism markers after second-line treatment with loading dose intravenous (i.v.) ibandronate in patients with bone metastases (BM) from breast cancer, 80 patients were enrolled in this study during January 2010 to April 2014. All the patients were treated with a second-line loading dose ibandronate for advanced breast cancer with BM and moderate-to-severe bone pain. Ibandronate (6 mg) was intravenously administered on three consecutive days followed by maintenance treatment every 3-4 weeks. Clinical data, including pain score, Karnofsky performance status (KPS) score, and changes in bone metabolism markers, were analyzed. Sixty-two patients were included in the final analysis. Compared with their pre-treatment scores, patients exhibited significantly increased KPS scores (P < .01) and a reduced dose of analgesic medication (oxycodone) (P < .01) after 3 and 6 weeks' post-treatment. The levels of serum bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP-5b), and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were significantly reduced after 3 and 6 weeks' post-treatment (P < .001). Aside from a few adverse events, no liver or renal toxicity was observed. Bone metabolism markers decreased by varying degrees after treatment with a loading dose of ibandronate in patients with BM from breast cancer. It might be convenient using bone metabolism markers to potentially evaluate the efficacy of bisphosphonates treatment for bone metastasis.
Background Anlotinib is a multi-targeted receptor tyrosine kinase inhibitor (TKI) which has exhibited encouraging clinical activity in advanced non-small cell lung cancer (NSCLC) and soft tissue sarcoma. Raltitrexed is well known to be effective in the treatment of colorectal cancer in China. The present study aims to investigate the combinatory antitumor effect of anlotinib and raltitrexed on human esophageal squamous carcinoma cells and further explore the molecular mechanisms in vitro. Methods Human esophageal squamous cell lines KYSE-30 and TE-1 were treated with anlotinib or raltitrexed, or both, then cell proliferation was measured by MTS and colony formation assay; cell migration and invasion were detected by wound-healing and transwell assays; cell apoptosis rate was studied by flow cytometry and the transcription of apoptosis-associated proteins were monitored by quantitative polymerase chain reaction (qPCR) analysis. Finally, western blot was performed to check phosphorylation of apoptotic proteins after treatment. Results Treatment with raltitrexed and anlotinib showed enhanced inhibitory effects on cell proliferation, migration and invasiveness compared with raltitrexed or anlotinib monotherapy. Meanwhile, raltitrexed combined with anlotinib strongly increased cell apoptosis percentage. Moreover, the combined treatment down-regulated mRNA level of the anti-apoptotic protein Bcl-2 and invasiveness-associated protein matrix metalloproteinases-9 (MMP-9), while up-regulated pro-apoptotic Bax and caspase-3 transcription. Western blotting showed that the combination of raltitrexed and anlotinib could inhibit the expression of phosphorylated Akt (p-Akt), Erk (p-Erk) and MMP-9. Conclusions This study indicated that raltitrexed enhanced the antitumor effects of anlotinib on human ESCC cells by down-regulating phosphorylation of Akt and Erk, providing a novel treatment option for patients with esophageal squamous cell carcinoma (ESCC).
Background: Estrogen could limit the nondominant follicles development after the first deviation by inhibition of the FSH secretion through the negative feedback loop, which ensure that the number of dominant follicles would be in a moderate level. Methods: The objective of the present study was to evaluate the effect of estradiol benzoate (EB) on inhibiting the development of nondominant follicles and inducing twin calves in beef heifers. Beef heifers were synchronized using an estradiol (E2)- plus- progesterone (P4)- based and superovulated using small dose follicle- stimulating hormone (FSH) protocol. From days 6.5 to 7.5 every heifer was treated with variety dose of estradiol benzoate (EB) for 3 times with 12 h intervals to eliminate the excess number of dominant follicles. Results: The diameters of the two largest follicles (F1 and F2) continually increased from day 3.5 to day 10. However, the growth rate was constrained by exogenous EB, and the degree of suppression was greatest in the 0.5 mg EB treatment compared with other treatments. As a result, the number of large follicles (≥ 10 mm) was also reduced along with the dose of EB increased. The double/triple ovulations rate, pregnancy rate and twin were all demonstrate the highest in 0.2 mg EB treatment group than in other treatments. Conclusions:The present study describes an efficient protocol that can be used to stimulate the development of a small number of dominant follicles i.e. 2-3 at the deviation stage through a FSH and 0.2 mg EB combine treatment, which can further result in the production of two calves. The appropriate dose of EB treatment during FSH induced superovulation procedure could limit the number of dominant follicles development and eventually increase the calf production efficiency.
BackgroundSmall cell lung cancer (SCLC) constitutes 15% of all lung cancer cases, with a comparatively low survival rate. The advent of immune checkpoint inhibitors (ICIs) has provided new alternatives for treating SCLC. However, the effectiveness of camrelizumab in the treatment of SCLC remains unclear. This retrospective case series was designed to investigate the efficacy and safety of camrelizumab in SCLC patients.MethodsThe study enrolled SCLC patients recorded as having received more than one cycle of camrelizumab in the electronic medical record system. Data related to clinical and survival times were collected and statistically analyzed.ResultsFrom August 2019 to December 2021, the study enrolled 12 SCLC patients. The objective response rate was 41.7% (95% confidence interval [CI]: 15.2%–72.3%). The disease control rate was 83.3% (95% CI: 51.6%–97.9%). The median progression-free survival (PFS) for all patients was 4.0 months. Notably, the median PFS of patients in third- or post-third-line subgroups was 7 months (95% CI: 1.12–12.88 months). The median overall survival (OS) for all eligible patients was 10.0 months (95% CI: 7.35–12.65 months), with a 1-year survival rate of 25%. Notably, the OS of patients treated with third- or post-third-line therapy was 5–34 months, with a 1-year survival rate of 75%. The two most prevalent non-hematological adverse events associated with the immune response were pneumonitis (44.4%) and reactive cutaneous capillary endothelial proliferation (44.4%). One patient experienced an exacerbation of preexisting diabetes and reached grade 3 hyperglycemia. There were no grade 4/5 immune-related adverse events.ConclusionThis case series highlights the potential benefits and safety concerns of camrelizumab in SCLC patients. These findings suggest a possible strategy for third- and post-third-line treatments of SCLC. However, the conclusion is limited due to the study’s retrospective nature and small sample size. Therefore, large-scale randomized controlled studies are needed to determine its efficacy.
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