[Effect of progesterone receptor status on efficacy of aromatase inhibitors and survival time in patients with advanced breast cancer].

To investigate the effect of progesterone receptor (PR) on the efficacy of first-line aromatase inhibitor (AI) endocrine therapy and progression-free survival (PFS) in patients with estrogen receptor (ER) positive HER-2 negative advanced breast cancer. The clinical data of 198 patients with advanced breast cancer treated in Henan Cancer Hospital from January 2014 to October 2019 were collected. The Chi-square test was used to compare the difference between the two groups, and the Cox regression model was used to analyze the related prognostic factors. The median progression-free survival time ((PFS)) of PR+and PR- patients were 12.5 months and 9.0 months, respectively, and the difference was statistically significant (P=0.004). The clinical benefit rate (CBR) was 81.1% and 63.1%, respectively, and the difference was not statistically significant (P<0.001). PR is an independent prognostic factor of first-line AI endocrine therapy in ER-positive HER-2-negative patients. PR+type breast cancer has a better response to first-line AI endocrine therapy and longer PFS time than PR- type advanced breast cancer.

[Clinical observation of palbociclib combined with endocrine therapy in hormone receptor positive and HER2 negative advanced breast cancer].

Objective: To analyze the application, efficacy, and safety of palbociclib in hormone receptor positive (HR+) and HER2 negative (HER2-) advanced breast cancer in the real world. Methods: The information of patients who received palbociclib treatment from September 2018 to September 2020 was collected, and the general medical history data and disease characteristics were summarized. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and safety were analyzed. Results: A total of 55 patients with HR+/HER2-advanced breast cancer who received a treatment regimen containing palbociclib were enrolled. The ORR was 48.8%, and DCR was 88.4%. The median PFS was 12.0 months (95%CI, 11.1-13.0 months), and the median TTF was 8.50 months (95%CI, 2.5-14.5 months). Among them, palbociclib was superior to multi-line therapy in the first line (P=0.000 1). The prognosis of patients with non-liver metastases was better (P=0.01). Hematological toxicity was the focus of observation of adverse events, including leukopenia, neutropenia, and thrombocytopenia. The incidence rates of them were 78.2%, 85.5%, and 34.5%, respectively. No other grade 3-4 nonhematological toxicity was found. Conclusions: Palbociclib combined with endocrine therapy in patients with HR+/HER2-advanced breast cancer has good efficacy and controllable adverse reactions. It can be used as a first-line or multi-line treatment option for HR+/HER2-advanced breast cancer.

[Clinical observation of apatinib mesylate for the treatment of multi-drug resistant advanced breast cancer].

Objective: To assess the clinical efficacy and adverse outcomes of apatinib mesylate for the treatment of multi-drug resistant advanced breast cancer. Methods: A total of 24 patients with multi-drug-resistant advanced breast cancer who underwent apatinib mesylate treatment were retrospectively analyzed at the Diagnosis and Treatment Center for Breast Cancer of Henan Cancer Hospital. Patients were reviewed every 4 weeks after initial treatment and then every 8 weeks after stable disease. Objective response rate (ORR), progression free survival (PFS), overall survival (OS) , toxicity and adverse outcomes of apatinib mesylate treatment were evaluated by imaging examinations. Results: Totally, 24 patients received apatinib mesylate at a dose of 500 mg QD. Out of the 24 patients treated, complete remission (CR) occurred in none of the patients, partial remission (PR) in 10 cases, stable disease (SD) in 10 cases, progressive disease (PD) in 4 cases, and drug with drawal in 2 cases due to adverse outcomes. Treatment with apatinib mesylate resulted in an ORR of 41.7% (10/24), disease control rate (DCR) of 83.3%, PFS of 4.7 months, and OS of 8.0 months. Adverse outcomes included proteinuria, high blood pressure, fatigue, hand-foot skin reaction (HFSR), hyperbilirubinemia, leukopenia, hair/skin pigmentation decreased. Most of the adverse events were tolerable and can be controlled after symptomatic management. Conclusions: Single-agent apatinib mesylate demonstrated the good short-term efficacy for multi-drug resistant advanced breast cancer in patients who previously underwent multiple line treatment failures. Adverse effects were controllable after symptomatic management. Treatment with apatinib mesylate maybe a viable option when other treatment modalities failed.

[Synergistic lethal effect of combined treatment of arsenic trioxide and aclacinomycin on human acute myeloid leukemia cell line KG-1a].

Objective: To investigate the synergistic lethal effect and mechanism of arsenic trioxide (ATO) and aclacinomycin (ACM) on human acute myeloid leukemia cell line KG-1a. Methods: Colony-forming assay was used to detect the proliferation of KG-1a cells treated with different concentration of ATO and ACM. Compusyn software was used to analyze the synergistic effect of ATO and ACM. Flow cytometry and Wright's staining were used to analyze the apoptotic rate of KG-1a cells induced by combined treatment of ATO and ACM. Western blot was used to determine the expression of proteins associated with apoptosis. Results: The cytotoxicity of arsenic trioxide or aclacinomycin alone was in a dose-dependent manner. Flow cytometry analysis showed that the apoptotic rate of KG-1a cells treated with both 0.4 µmol/L ATO and 10 nmol/L ACM was (34.5±3.1)%, significantly higher than (7.6±1.1)% of 0.4 µmol/L ATO treatment or (18.7±2.3) % of 10 nmol/L ACM treatment alone (P<0.05). The apoptotic rate of KG-1a cells treated with both 1.5 µmol/L ATO and 37.5 nmol/L ACM was (52.5±4.7)%, significantly higher than (19.1±3.2)% of 1.5 µmol/L ATO treatment or (27.7±2.2)% of 37.5 nmol/L ACM treatment alone (P<0.05). The apoptotic rate of KG-1a cells treated with both 3.0 µmol/L ATO and 75 nmol/L ACM was (61.3±4.5)%, significantly higher than (29.5±2.5)% of 3.0 µmol/L ATO treatment or (28.6±3.4) % of 75 nmol/L ACM treatment alone (P<0.05). In addition, the result of Wright's staining showed that combined treatment of ATO and ACM induced a more apparent phenotype of apoptosis when compared with single agent treatment. Compusyn software analysis showed that the combination index (CI) value of combined treatment group was less than 1, which indicated the synergistic effect of these two agents. Conclusions: Combined treatment of ATO and ACM shows a synergistic lethal effect on human acute myeloid leukemia cell line KG-1a via activating the apoptotic pathway, which inhibits cell growth and induces apoptosis.

Associations of lifestyle-related factors, hsa-miR-149 and hsa-miR-605 gene polymorphisms with gastrointestinal cancer risk.

To explore the associations of SNPs within hsa-miR-605 (rs2043556) and hsa-miR-149 (rs2292832) and lifestyle-related factors with gastrointestinal cancer, a case-control study including 762 cases and 757 controls was conducted. Marginally significant associations were found both for hsa-miR-149 rs2292832 with gastric cancer risk (TC + CC vs. TT, OR = 0.68, 95% CI: 0.44-1.04) and for hsa-miR-605 rs2043556 with colorectal cancer risk (AG + GG vs. AA, OR = 0.70, 95% CI: 0.48-1.02) in males. Tea drinking showed a protective effect on gastric cancer risk (OR = 0.28, 95% CI: 0.13-0.60), while smoke inhalation increased the risk of gastric cancer (OR = 1.94, 95% CI: 1.08-3.47). Irritability was found to be a risk factor for both colorectal cancer (OR = 1.61, 95% CI: 1.02-2.53) and gastric cancer (OR = 1.96, 95% CI: 1.17-3.29). Among those that engaged in smoke inhalation, miR-149 CT/CC and miR-605 AG/GG genotype carriers had increased susceptibilities to colorectal cancer (OR = 1.90, 95% CI: 1.11-3.25) and gastric cancer (OR = 1.87, 95% CI: 1.03-3.42), respectively. Among the tea drinkers, there exists a marginally protective effect of miR-605 AG/GG genotypes on colorectal cancer incidence (OR = 0.71, 95% CI: 0.47-1.06) and a significantly protective effect of miR-149 CT/CC on gastric cancer incidence (OR = 0.47, 95% CI: 0.29-0.77). The SNPs of rs2292832 and rs2043556 might be able to modify the susceptibility to male gastric and colorectal cancers, respectively. Tea drinking is a protective factor, while smoke inhalation is a risk factor for gastric cancer, and they might have the potential to modify the associations between miR-149 and miR-605 polymorphisms with gastrointestinal cancer risk. In addition, irritability was shown to be a risk factor for both gastric and colorectal cancers.

[Effects of murine lymphokine-activated killer (LAK) cells on proliferation of myeloid progenitor cells (CFU-GM)].

Murine lymphokine-activated killer (LAK) cells were generated from spleen cells of C57/BL6 mice by culture of spleen cells in vitro for 72 hours in medium containing 500 units/ml recombinant human interleukin 2 (IL-2), and effects of these LAK cells on proliferation of syngenic myeloid progenitor cells (CFU-GM) were observed. After 3 days culture, LAK cells were assayed for their cytotoxicity in a 4 hours 51Cr-release test. Either natural killer (NK) cell sensitive YAC-1 lymphoma cells or NK cell resistant LP-3 and WEHI-164 fibrosarcoma cells were efficiently lysed by murine LAK cells. When LAK cells were added into culture system in a final concentration of 5 x 10(4)/ml, 2 x 10(5)/ml, 8 x 10(5)/ml, CFU-GM were increased by 55.2%, 165.5%, and 194.4% of control respectively. LAK-CM also showed augmentative effect on CFU-GM growth. When 10% (v/v) of LAK-CM were added into culture system, CFU-GM were increased by 51.4% of control, but LAK-CM alone could not stimulate CFU-GM growth. Again, effects of LAK-BMC interaction on CFU-GM formation were investigated. CFU-GM were inhibited to 27.6% of control when 1 x 10(5) BMC were mixed with 8 x 10(5) LAK cells and incubated for 4 hours prior to CFU-GM culture. These data suggest that (1) LAK cells may secrete co-CSF which showed synergistic effect with CSF on CFU-GM proliferation: (2) When LAK cells contact with BMC, they showed significant cytotoxicity to myeloid progenitor cells which mediated decrease of CFU-GM formation.

Modulating activity of B lymphocytes on haemopoiesis (II)--the purification of proliferation amplifying factor (PAF).

In recent years we have done a series of observations on the haemopoietic modulation effects of lymphocytes. Now we report here, for the first time, the purification of a modulating factor (proliferation amplifying factor, PAE) with affinity chromatography and HPLC from supernatant conditioned by a lymphoma cell line M12.4.1. RAF exhibits on SDS-PAGE only one band, the molecular weight is about 31,000, the specific activity is 20,000 times that in the conditioned medium. It may provide a direct evidence that the B lymphocyte also possesses some haemopoietic modulation effects.