Comparative efficacy & safety of buparlisib plus fulvestrant, fulvestrant plus dalpiciclib, and ribociclib plus letrozole for postmenopausal, hormone receptor-positive, and HER2-negative breast cancer

Abstract Objectives: This study aimed to compare progression-free survival, overall survival, clinical benefits, and adverse effects in postmenopausal women with hormone receptor-positive and HER2-negative breast cancer who received buparlisib plus fulvestrant against those of women who received dalpiciclib plus fulvestrant, considering ribociclib plus letrozole treatment as the reference standard. Methods: Women received buparlisib plus fulvestrant (BF cohort, n = 108), dalpiciclib plus fulvestrant (DF cohort, n = 132), or ribociclib plus letrozole (RL cohort, n = 150) until unacceptable toxicity was observed. Results: A total of 117 (89 %), 80 (74 %), and 84 (56 %) women in the BF, DF, and RL cohorts, respectively, had clinical benefits. After treatment, the clinical benefits for women and after 42 months of follow-up progression-free survival and overall survival were higher in the DF cohort than in the BF and RL cohorts (p < 0.05 for all). Neutropenia, vomiting, constipation, nausea, diarrhea, and anorexia were reported higher in women of the DF and BF cohorts than in women of the RL cohort. Leukopenia and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the RL cohort than in women in the DF and BF cohorts. Depression, anxiety, and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the BF cohort than in women in the DF and RL cohorts. Conclusions: Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

Esophageal metastasis secondary to extranodal nasal-type natural killer/T-cell lymphoma: A case report.

We herein report a case of recurrent nasal natural killer (NK)/T-cell lymphoma in a 21-year-old male patient. The patient presented with an esophageal mass, fever and difficulty in swallowing. There were no other obvious sites of recurrence apart from the esophageal lesion. Metastatic esophageal lesions are extremely rare. The histological analysis demonstrated a highly aggressive tumor with a characteristic angiodestructive growth pattern and nasal cavity necrosis. The lymphoma cells were immunopositive for leukocyte common antigen, T-cell intracytoplasmic antigen 1 and CD68, negative for CD56 and CD3, and positive for Epstein-Barr virus. A computed tomography scan revealed mild thickening of the wall of the lower esophagus. The barium swallow revealed stiffness of the esophageal wall, with limited expansion and mucosal damage. The final diagnosis was primary nasal NK/T-cell lymphoma, with metastasis to the esophagus. Clinically, it is important to distinguish nasal-type NK/T-cell lymphoma from other types of tumors, as its prognosis and treatment of secondary metastases differ significantly.

Green synthesis of biocompatible carboxylic curdlan-capped gold nanoparticles and its interaction with protein.

This study demonstrates a facile, green strategy for the preparation of gold nanoparticles (AuNPs) from chloroauric acid (HAuCl4) using carboxylic curdlan (Cc) as both reducing and stabilizing agent. The as-prepared AuNPs are characterized by UV-vis spectroscopy, high resolution transmission electron microscopy, X-ray diffraction, energy dispersive X-ray spectrometry and Fourier transform infrared spectroscopy. The results indicated that the particle size of the AuNPs changes with variations in the reaction time and concentrations of Cc and HAuCl4. The spherical AuNPs are well dispersed, exhibiting high stability even after six months storage. The carboxylic groups (COO(-)) in the Cc molecules tend to adsorb and stabilize the surface of the AuNPs. The interaction between BSA and the Cc-capped AuNPs was investigated using fluorescence and circular dichroism spectroscopies. The results indicated that the BSA molecules adsorb on the surface of the AuNPs, without significant change in its helical structure even after conjugation with the AuNPs.

The clinical value of serum hepatocyte growth factor levels in patients undergoing primary radiotherapy for glioma: effect on progression-free survival.

Hepatocyte growth factor (HGF) has been shown to be overexpressed in gliomas, and high-grade gliomas (glioblastoma multiforme) express more HGF than lower-grade astrocytoma, and HGF enhances their resistance to radiotherapy. To examine the effect of serum HGF levels on the likelihood of response to radiotherapy and the disease-free survival in patients with glioma, the blood samples of the patients were collected before commencing treatment and serum HGF was measured by quantitative ELISA in 48 patients with glioma grade I-IV, and all patients underwent primary conventionally fractionated radiotherapy. For statistical analysis, SPSS Version 13.0 software was used. Thirty-eight of the 48 patients had a response to treatment, and ten patients had persistent disease at 3 months. Overall, the median serum HGF level was 1,219.5 pg/ml (range 650.4-2,264.7 pg/ml). Eight patients with local failure had HGF levels >1,219.5 pg/ml, and 28 patients with response had serum HGF level of ≤ 1,219.5 pg/ml (P = 0.01). The median time to progression was 6 months in patients with HGF level of >1,219.5 pg/ml compared with 17 months in patients with HGF level of ≤ 1,219.5 pg/ml (log-rank, P = 0.041). In multivariate analysis, serum HGF, the KPS, tumour size and pathological grade, but not the patient's age, gender and oligodendroglial component influenced the progression-free survival. Elevated pre-therapeutic serum HGF levels are associated with poor response and a shorter time to progression in patients with glioma undergoing primary radiotherapy.

A study on the inhibitory effect of matrine on gastric cancer SGC-7901 cells.

The objective of this paper was to investigate the antitumour mechanism of action of matrine by studying its inhibitory effect on gastric cancer SGC-7901 cells. SGC-7901 cells were chosen, and cell-killing capacity of matrine on gastric cancer SGC-7901 cells was determined using MTT assay and single PI staining assay. The results showed that matrine had an inhibitory effect on gastric cancer SGC-7901 cells, which was somewhat dose-dependent. The study concluded that matrine has a significant in-vitro inhibitory effect on SGC-7901 tumour cells, influences cell cycle of SGC-7901 cells, and induces their apoptosis.

Pdx1 protein induces human embryonic stem cells into the pancreatic endocrine lineage.

Success in generating insulin-producing cells (IPCs) from human embryonic stem (hES) cells by genetic manipulation has recently revealed a new therapeutic potential for diabetes. However, clinical application has been hampered by the viral genome integration and the risk of insertion mutagenesis that are entailed. Herein, we report the induction of hEC into IPCs by direct delivery of human Pdx1 proteins per se. Recombinant human Pdx1 proteins (hPdx1), which have an Antennapedia-like protein transduction domain sequence in their structure, can be efficiently translocated into hES cells and function as pancreatic transcription factor. hPdx1 protein activates a group of genes related to pancreatic beta-cell lineage development in hES cells, including NeuroD1, Nkx2.2, Pax4, Pax6, Nkx6.1 and Isl-1. hPdx1-treated hES cells synthesise and release insulin in response to glucose challenge. Therefore, this study constitutes a proof-of-concept demonstration of protein-mediated pancreatic specific differentiation of the hES cells by exploiting specific intrinsic properties of the hPdx1 protein.

[Lishengsu promotes the recovery of chemotherapy-induced leukopenia in patients with malignant tumors].

In order to investigate the therapeutic effects of Lishengsu, a domestic preparation of recombinant human granulocyte colony stimulating factor, the recovery of leukopenia was observed in 58 patients with malignant tumors after chemotherapy. In these patients, 7 cases were in first cycle of chemotherapy and 51 were given in repeated cycles. When blood leukocyte level decreased to less than 3x10(9)/L, Lishengsu was subcutaneously injected for 3-5 days at a dose of 75 microgram or 150 microgram per day. The results showed that Lishengsu remarkably alleviated the degree of leukopenis and accelerated the leukocyte counts recovered to normal level. The promotive effects of Lishengsu to recovery of leukopenia were dependent on degree of leukopenia at start of administration of Lishengsu. The curative effect of Lishengsu to chemotherapy-induced leukopenia was reliable with slight side-effects