Genome-wide identification, classification and expression analysis of the heat shock transcription factor family in Garlic (Allium sativum L.).

BACKGROUND: The heat shock transcription factor (HSF) plays a crucial role in the regulatory network by coordinating responses to heat stress as well as other stress signaling pathways. Despite extensive studies on HSF functions in various plant species, our understanding of this gene family in garlic, an important crop with nutritional and medicinal value, remains limited. In this study, we conducted a comprehensive investigation of the entire garlic genome to elucidate the characteristics of the AsHSF gene family. RESULTS: In this study, we identified a total of 17 AsHSF transcription factors. Phylogenetic analysis classified these transcription factors into three subfamilies: Class A (9 members), Class B (6 members), and Class C (2 members). Each subfamily was characterized by shared gene structures and conserved motifs. The evolutionary features of the AsHSF genes were investigated through a comprehensive analysis of chromosome location, conserved protein motifs, and gene duplication events. These findings suggested that the evolution of AsHSF genes is likely driven by both tandem and segmental duplication events. Moreover, the nucleotide diversity of the AsHSF genes decreased by only 0.0002% from wild garlic to local garlic, indicating a slight genetic bottleneck experienced by this gene family during domestication. Furthermore, the analysis of cis-acting elements in the promoters of AsHSF genes indicated their crucial roles in plant growth, development, and stress responses. qRT-PCR analysis, co-expression analysis, and protein interaction prediction collectively highlighted the significance of Asa6G04911. Subsequent experimental investigations using yeast two-hybridization and yeast induction experiments confirmed its interaction with HSP70/90, reinforcing its significance in heat stress. CONCLUSIONS: This study is the first to unravel and analyze the AsHSF genes in garlic, thereby opening up new avenues for understanding their functions. The insights gained from this research provide a valuable resource for future investigations, particularly in the functional analysis of AsHSF genes.

Acremosides A-G, Sugar Alcohol-Conjugated Acyclic Sesquiterpenes from a Sponge-Derived Acremonium Species.

Seven new sugar alcohol-conjugated acyclic sesquiterpenes, acremosides A-G (1-7), were isolated from the cultures of the sponge-associated fungus Acremonium sp. IMB18-086 cultivated with heat-killed Pseudomonas aeruginosa. The structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data. The relative configurations were established by J-based configuration analysis and acetonide derivatization. The absolute configurations were elucidated by the Mosher ester method and ECD calculations. The structures of acremosides E-G (5-7) featured the linear sesquiterpene skeleton with a tetrahydrofuran moiety attached to a sugar alcohol. Acremosides A (1) and C-E (3-5) showed significant inhibitory activities against hepatitis C virus (EC50 values of 4.8-8.8 µM) with no cytotoxicity (CC50 of >200 µM).

Antimicrobial and Anti-inflammatory Cyclic Tetrapeptides from the Co-cultures of Two Marine-Derived Fungi.

Violaceotides B-E (1-4), four new cyclic tetrapeptides, along with seven known compounds, were identified from the sponge-associated Aspergillus insulicola IMB18-072 co-cultivated with the marine-derived Alternaria angustiovoidea IMB20-805. Their structures were elucidated by extensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and MS/MS data. The absolute configurations were determined by the advanced Marfey's method. Compounds 2, 3, and violaceotide A (5) displayed selective antimicrobial activities against the aquatic pathogenic bacteria Edwardsiella tarda and E. ictaluri. In addition, compounds 1-5 showed inhibitory activities against the LPS-induced expression of the inflammatory mediator IL-6 in RAW264.7 cells at a concentration of 10 µM.

Isolation, Structure Elucidation, and First Total Synthesis of Quinomycins K and L, Two New Octadepsipeptides from the Maowei Sea Mangrove-Derived Streptomyces sp. B475.

Mangrove actinomycetia have been proven to be one of the promising sources for discovering novel bioactive natural products. Quinomycins K (1) and L (2), two rare quinomycin-type octadepsipeptides without intra-peptide disulfide or thioacetal bridges, were investigated from the Maowei Sea mangrove-derived Streptomyces sp. B475. Their chemical structures, including the absolute configurations of their amino acids, were elucidated by a combination of NMR and tandem MS analysis, electronic circular dichroism (ECD) calculation, advanced Marfey's method, and further unequivocally confirmed by the first total synthesis. The two compounds displayed no potent antibacterial activity against 37 bacterial pathogens and had no significant cytotoxic activity against H460 lung cancer cells.

Dynamic network biomarker analysis discovers IbNAC083 in the initiation and regulation of sweet potato root tuberization.

The initiation and development of storage roots (SRs) are intricately regulated by a transcriptional regulatory network. One key challenge is to accurately pinpoint the tipping point during the transition from pre-swelling to SRs and to identify the core regulators governing such a critical transition. To solve this problem, we performed a dynamic network biomarker (DNB) analysis of transcriptomic dynamics during root development in Ipomoea batatas (sweet potato). First, our analysis identified stage-specific expression patterns for a significant proportion (>9%) of the sweet potato genes and unraveled the chronology of events that happen at the early and later stages of root development. Then, the results showed that different root developmental stages can be depicted by co-expressed modules of sweet potato genes. Moreover, we identified the key components and transcriptional regulatory network that determine root development. Furthermore, through DNB analysis an early stage, with a root diameter of 3.5 mm, was identified as the critical period of SR swelling initiation, which is consistent with morphological and metabolic changes. In particular, we identified a NAM/ATAF/CUC (NAC) domain transcription factor, IbNAC083, as a core regulator of this initiation in the DNB-associated network. Further analyses and experiments showed that IbNAC083, along with its associated differentially expressed genes, induced dysfunction of metabolism processes, including the biosynthesis of lignin, flavonol and starch, thus leading to the transition to swelling roots.

Starch synthase II plays a crucial role in starch biosynthesis and the formation of multienzyme complexes in cassava storage roots.

Starch is a glucose polymer synthesized by green plants for energy storage and is crucial for plant growth and reproduction. The biosynthesis of starch polysaccharides is mediated by members of the large starch synthase (SS) protein superfamily. Here, we showed that in cassava storage roots, soluble starch synthase II (MeSSII) plays an important role in starch biosynthesis and the formation of protein complexes with other starch biosynthetic enzymes by directly interacting with MeSSI, MeSBEII, and MeISAII. MeSSII-RNAi cassava lines showed increased amylose content and reduced biosynthesis of the intermediate chain of amylopectin (B1 type) in their storage roots, leading to altered starch physicochemical properties. Furthermore, gel permeation chromatography analysis of starch biosynthetic enzymes between wild type and MeSSII-RNAi lines confirmed the key role of MeSSII in the organization of heteromeric starch synthetic protein complexes. The lack of MeSSII in cassava also reduced the capacity of MeSSI, MeSBEII, MeISAI, and MeISAII to bind to starch granules. These findings shed light on the key components of the starch biosynthesis machinery in root crops.

Zelkovamycins F and G, Cyclopeptides with Cα-Methyl-threonine Residues, from an Endophytic Kitasatospora sp.

Zelkovamycins F and G (1 and 2), two new natural cyclic octapeptides possessing the unprecedented nonproteinogenic amino acid residues l-α-methyl-threonine and l-α-methyl-allo-threonine, respectively, along with four new analogues, zelkovamycins H-K (3-6), were identified from the endophytic Kitasatospora sp. CPCC 204717. Their structures were elucidated by detailed analysis of NMR and HRESIMS/MS spectroscopic data. The configurations of amino acid residues were determined by Marfey's analysis combined with NMR calculations. Compounds 1, 2, and 4 showed potent antibacterial activity against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. The structure-activity relationship study revealed that the 2-methyl-3-oxobutyrine and sarcosine residues played important roles in their antibacterial activities. Zelkovamycin (7) and zelkovamycin E (8) exhibited significant antiviral activity against the hepatitis C virus.

Genome-wide identification, phylogeny and expression analysis of AP2/ERF transcription factors family in sweet potato.

BACKGROUND: In recent years, much attention has been given to AP2/ERF transcription factors because they play indispensable roles in many biological processes, such as plant development and biotic and abiotic stress responses. Although AP2/ERFs have been thoroughly characterised in many plant species, the knowledge about this family in the sweet potato, which is a vital edible and medicinal crop, is still limited. In this study, a comprehensive genome-wide investigation was conducted to characterise the AP2/ERF gene family in the sweet potato. RESULTS: Here, 198 IbAP2/ERF transcription factors were obtained. Phylogenetic analysis classified the members of the IbAP2/ERF family into three groups, namely, ERF (172 members), AP2 (21 members) and RAV (5 members), which was consistent with the analysis of gene structure and conserved protein domains. The evolutionary characteristics of these IbAP2/ERF genes were systematically investigated by analysing chromosome location, conserved protein motifs and gene duplication events, indicating that the expansion of the IbAP2/ERF gene family may have been caused by tandem duplication. Furthermore, the analysis of cis-acting elements in IbAP2/ERF gene promoters implied that these genes may play crucial roles in plant growth, development and stress responses. Additionally, the available RNA-seq data and quantitative real-time PCR (qRT-PCR) were used to investigate the expression patterns of IbAP2/ERF genes during sweet potato root development as well as under multiple forms of abiotic stress, and we identified several developmental stage-specific and stress-responsive IbAP2/ERF genes. Furthermore, g59127 was differentially expressed under various stress conditions and was identified as a nuclear protein, which was in line with predicted subcellular localization results. CONCLUSIONS: This study originally revealed the characteristics of the IbAP2/ERF superfamily and provides valuable resources for further evolutionary and functional investigations of IbAP2/ERF genes in the sweet potato.

Acremopeptaibols A-F, 16-Residue Peptaibols from the Sponge-Derived Acremonium sp. IMB18-086 Cultivated with Heat-Killed Pseudomonas aeruginosa.

Six new 16-residue peptaibols, acremopeptaibols A-F (1-6), along with five known compounds, were isolated from the cultures of the sponge-associated fungus Acremonium sp. IMB18-086 grown in the presence of the autoclaved bacterium Pseudomonas aeruginosa on solid rice medium. The peptaibol sequences were established based on comprehensive analysis of 1D and 2D NMR spectroscopic data in conjunction with HRESIMS/MS experiments. The configurations of the amino acid residues were determined by advanced Marfey's analysis. Compounds 1-6 feature the lack of the highly conserved Thr6 and Hyp10 residues in comparison with other members of the SF3 subfamily peptaibols. A plausible biosynthetic pathway of compounds 1-6 was proposed on the basis of genomic analysis. Compounds 1, 5, 7, and 10 exhibited significant antimicrobial activity against Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Candida albicans. Compounds 7-10 showed potent cytotoxicities against the A549 and/or HepG2 cancer cell lines.

Production of very-high-amylose cassava by post-transcriptional silencing of branching enzyme genes.

High amylose starch can be produced by plants deficient in the function of branching enzymes (BEs). Here we report the production of transgenic cassava (Manihot esculenta Crantz) with starches containing up to 50% amylose due to the constitutive expression of hair-pin dsRNAs targeting the BE1 or BE2 genes. All BE1-RNAi plant lines (BE1i) and BE2-RNAi plant lines (BE2i) were grown up in the field, but with reduced total biomass production. Considerably high amylose content in the storage roots of BE2i plant lines was achieved. Storage starch granules of BE1i and BE2i plants had similar morphology as wild type (WT), however, the size of BE1i starch granules were bigger than that of WT. Comparisons of amylograms and thermograms of all three sources of storage starches revealed dramatic changes to the pasting properties and a higher melting temperature for BE2i starches. Glucan chain length distribution analysis showed a slight increase in chains of DP>36 in BE1i lines and a dramatic increase in glucan chains between DP 10-20 and DP>40 in BE2i lines. Furthermore, BE2i starches displayed a B-type X-ray diffraction pattern instead of the A-type pattern found in BE1i and WT starches. Therefore, cassava BE1 and BE2 function differently in storage root starch biosynthesis.

Differential response to neoadjuvant hormonal therapy in prostate cancer: Predictive morphological parameters and molecular markers.

OBJECTIVES: The predictive value of the histological parameters and molecular markers for neoadjuvant hormonal therapy (NHT) in prostate cancer (PCa) has not been well established. The aim of this study is to determine pathological variables that can predict differences in response to NHT in PCa. METHODS: A total of 85 locally high risk PCa patients with matched preoperative needle biopsies and radical prostatectomy (RP) specimens were included. All patients were treated with NHT for at least 3 months. We quantified the response to NHT using a new proposed pathological grading system. The system classified tumors into five groups (grades 0-4) according to the severity of histological response. We then categorized the PCa patients into drug-sensitive (DS) group (Grades 2-4) and drug-resistant (DR) group (Grades 0-1). Two pathologists assessed each pretreated tumors for presence or absence of nine morphological features. The expression of androgen receptor (AR), ERG, and PTEN were evaluated by immunohistochemistry (IHC) as well. Statistical analysis was performed to identify significant associations between differentially histological response to NHT and morphological features as well as molecular aberrations. We evaluated different prediction models using receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) analysis. RESULTS: 73% (n = 62/85) of tumors in our cohort belonged to DS group, whereas 27% (n = 23/85) of tumors were DR. Univariate logistic analysis suggested four pathological variables, cribriform growth pattern, macronucleoli, ductal adenocarcinoma differentiation, and PTEN loss in needle biopsies were significantly associated with DR effect, all with P-value < 0.05. Multivariate logistic regression analysis revealed that the three parameters as significant predictive factors for predicting DR effect. These were macronucleoli (RR = 4.008, P = 0.002), ductal adenocarcinoma differentiation (RR = 11.659, P = 0.009) and PTEN loss expression (RR = 7.275, P = 0.015). The AUC of three integrated indicators model was 0.781. CONCLUSIONS: Our study suggested that the presence of tumor cribriform growth pattern, macronucleoli, ductal adenocarcinoma differentiation, and PTEN loss in needle biopsies are of value in predicting tumor response to NHT regimen. Multivariate logistic regression analysis revealed the performance of combined pathological indicators in predicting DR response was better than that of model based on individual factor alone.

Raistrickindole A, an Anti-HCV Oxazinoindole Alkaloid from Penicillium raistrickii IMB17-034.

Raistrickindole A (1), a new indole diketopiperazine alkaloid containing an unusual pyrazino[1',2':2,3][1,2]oxazino[6,5- b]indole tetraheterocyclic ring system, a new benzodiazepine derivative, raistrickin (2), and the known haenamindole (3) and sclerotigenin (4) were isolated from the marine-derived fungus Penicillium raistrickii IMB17-034. Their structures were elucidated by extensive spectroscopic analyses and TDDFT calculations of the NMR and ECD data. Compounds 1 and 2 showed inhibitory activities against the hepatitis C virus.

Broad-Spectrum Antiviral Natural Products from the Marine-Derived Penicillium sp. IMB17-046.

A new pyrazine derivative, trypilepyrazinol (1), a new α-pyrone polyketide, (+)-neocitreoviridin (2), and a new ergostane analogue, 3ß-hydroxyergosta-8,14,24(28)-trien-7-one (3), were isolated and characterized along with five known compounds from the marine-derived fungus Penicillium sp. IMB17-046. The structures of these new compounds were determined using spectroscopic data analyses (HRESIMS, 1D- and 2D-NMR), X-ray crystallography analysis, and TDDFT ECD calculation. Compounds 1 and 3 exhibited broad-spectrum antiviral activities against different types of viruses, including human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza A virus (IAV), with IC50 values ranging from 0.5 to 7.7 µM. Compounds 1 and 2 showed antibacterial activities against Helicobacter pylori, a causative pathogen of various gastric diseases, with minimum inhibitory concentration (MIC) values of 1-16 µg/mL.

Identification and Proposed Relative and Absolute Configurations of Niphimycins C-E from the Marine-Derived Streptomyces sp. IMB7-145 by Genomic Analysis.

Analysis of the whole genome sequence of Streptomyces sp. IMB7-145 revealed the presence of seven type I polyketide synthase biosynthetic gene clusters, one of which was highly homologous to the biosynthetic gene cluster of azalomycin F. Detailed bioinformatic analysis of the modular organization of the PKS gene suggested that this gene is responsible for niphimycin biosynthesis. Guided by genomic analysis, a large-scale cultivation ultimately led to the discovery and characterization of four new niphimycin congeners, namely, niphimycins C-E (1-3) and 17-O-methylniphimycin (4). The configurations of most stereocenters of niphimycins have not been determined to date. In the present study, the relative configurations were elucidated by spectroscopic analysis, including J-based analysis and the CNMR database method. Further, the full absolute configurations of niphimycins were completely proposed for the first time based on biosynthetic gene cluster analysis of the ketoreductase and enoylreductase domains for hydroxy- and methyl-bearing stereocenters. Compounds 1, 3, 4, and niphimycin Iα (5) showed antimicrobial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci (MIC: 8-64 µg/mL), as well as cytotoxicity against the human HeLa cancer cell line (IC50: 3.0-9.0 µM). In addition, compounds 1 and 5 displayed significant activity against several Mycobacterium tuberculosis clinical isolates (MIC: 4-32 µg/mL).

Seco-Tetracenomycins from the Marine-Derived Actinomycete Saccharothrix sp. 10-10.

Six new tetracenomycin congeners, saccharothrixones E⁻I (1⁻5) and 13-de-O-methyltetracenomycin X (6), were isolated from the rare marine-derived actinomycete Saccharothrix sp. 10-10. Their structures were elucidated by spectroscopic analysis and time-dependent density functional theory (TDDFT)-electronic circular dichroism (ECD) calculations. Saccharothrixones G (3) and H (4) are the first examples of tetracenomycins featuring a novel ring-A-cleaved chromophore. Saccharothrixone I (5) was determined to be a seco-tetracenomycin derivative with ring-B cleavage. The new structural characteristics, highlighted by different oxidations at C-5 and cleavages in rings A and B, enrich the structural diversity of tetracenomycins and provide evidence for tetracenomycin biosynthesis. Analysis of the structure⁻activity relationship of these compounds confirmed the importance of the planarity of the naphthacenequinone chromophore and the methylation of the polar carboxy groups for tetracenomycin cytotoxicity.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate firing of globus pallidus neurons in vivo.

The globus pallidus plays a significant role in motor control under both health and pathological states. Recent studies have revealed that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels occupy a critical position in globus pallidus pacemaking activity. Morphological studies have shown the expression of HCN channels in the globus pallidus. To investigate the in vivo effects of HCN channels in the globus pallidus, extracellular recordings and behavioral tests were performed in the present study. In normal rats, micro-pressure ejection of 0.05mM ZD7288, the selective HCN channel blocker, decreased the frequency of spontaneous firing in 21 out of the 40 pallidal neurons. The average decrease was 50.4±5.4%. Interestingly, in another 18 out of the 40 pallidal neurons, ZD7288 increased the firing rate by 137.1±27.6%. Similar bidirectional modulation on the firing rate was observed by a higher concentration of ZD7288 (0.5mM) as well as another HCN channel blocker, CsCl. Furthermore, activation of HCN channels by 8-Br-cAMP increased the firing rate by 63.0±9.3% in 15 out of the 25 pallidal neurons and decreased the firing rate by 46.9±9.4% in another 8 out of the 25 pallidal neurons. Further experiments revealed that modulation of glutamatergic but not GABAergic transmission may be involved in ZD7288-induced increase in firing rate. Consistent with electrophysiological results, further studies revealed that modulation of HCN channels also had bidirectional effects on behavior. Taken together, the present studies suggest that HCN channels may modulate the activity of pallidal neurons by different pathways in vivo.

[Efficacy and safety analysis of paclitaxel liposome and docetaxel for the neoadjuvant chemotherapy of breast cancer].

OBJECTIVE: The aim of this study was to analyze the efficacy and safety of paclitaxel liposomal and docetaxel for neoadjuvant chemotherapy of breast cancer. METHODS: We retrospectively analyzed the clinical data of 188 operable patients with breast cancer who received neoadjuvant chemotherapy. According to the treatment regimens, they were divided into the group of paclitaxel liposome (86 patients) and group of docetaxel (102 patients) treatment. All the patients received a combination therapy with epirubicin and cyclophosphamide, i.e. neoadjuvant chemotherapy with three drugs, 21 days as a cycle, and a total of 6 cycles. Surgery was carried out three weeks after the end of chemotherapy, and the chemotherapy efficacy and adverse reaction of both groups were evaluated. RESULTS: Pathological complete response (pCR) rate in the paclitaxel liposome group and docetaxel group was 10.5% and 9.8%, respectively, the objective response rate (ORR) was 80.2% and 79.4%, respectively, and the disease control rate (DCR) was 95.3% and 93.1%, respectively, showing a non-significant difference in therapy efficacy between the two groups (P > 0.05). Safety analysis indicated that all the occurrence rates of skin and nail toxic reaction, body fluid retention, oral mucositis, allergic reaction (such as facial blushing, chest distress, palpitation, dyspnea. etc.), and grade III-IV leukopenia and neutropenia in the paclitaxel liposome group were significantly lower than that of the docetaxel group (all P < 0.05). CONCLUSIONS: Compared with docetaxel, paclitaxel liposome has the same anti-tumor efficacy, but causes fewer and milder adverse reactions with a higher safety in the neoadjuvant chemotherapy for breast cancer.

Clinical pathological characteristics and prognostic analysis of diabetic women with luminal subtype breast cancer.

This study selected luminal-type breast cancer patients as the study subjects. The patients were divided into groups according to the presence of diabetes and the types of medication used, and the patients' clinicopathological characteristics and prognostic indicators were explored. A total of 5,785 patients with luminal-type breast cancer admitted to Tianjin Medical University Cancer Institute and Hospital between January 2002 and December 2006 were selected as the study subjects. The subjects included 680 breast cancer patients with diabetes and 5,105 breast cancer patients without diabetes. The patients were divided into Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes. Each subtype was further divided into a metformin group, a non-metformin group, and a nondiabetic group. The research indicators included breast cancer mortality, age, body mass index (BMI), amenorrhea, the presence of cardiovascular and cerebrovascular disease, pathological stage, pathological type, lymph node involvement, vessel carcinoma embolus, and the chemotherapy and endocrine regimen. A Kaplan-Meier analysis was conducted to analyze the differences in breast cancer mortality rates among the groups. The Cox proportional hazard model was adopted to detect independent factors related to prognosis. Kaplan-Meier univariate analysis showed that for the Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes, the cancer-specific mortality rates differed significantly among the metformin, non-metformin, and nondiabetic groups. The 5-year survival rates were 94%, 82%, and 91% (P = 0.002); 93.5%, 81%, and 89% (P < 0.001); and 84%, 77%, and 83% (P = 0.035) for the subtypes within each group, respectively. Cox regression multivariate analysis showed that compared with the metformin group, all three subtypes of the, the non-metformin group showed poorer prognosis (hazard ratio [HR], 3.579; 95% confidence interval [CI], 1.506-8.506 [P = 0.004]; HR, 3.232; 95% CI, 1.839-5.678 [P < 0.001]; HR, 2.034; 95% CI,1.019-4.059 [P = 0.044] for Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+, respectively). Compared with the metformin group, the diabetic group showed poorer prognosis only for the Luminal B (high ki67) subtype (HR, 1.762; 95% CI, 1.033-3.005 [P = 0.038]). In addition, for the Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subgroups, there was a higher proportion of elderly patients (P < 0.001) and postmenopausal patients (P < 0.001) in the metformin and non-metformin groups than in the nondiabetic group. Moreover, the probability of having cardiovascular and cerebrovascular disease was also higher (P < 0.001) in the metformin and non-metformin groups. For the Luminal B (high ki67) and Luminal B (her-2/neu +) subgroups, there was a higher proportion of obese patients in the metformin and non-metformin groups (P < 0.001). In terms of clinical characteristics, for the Luminal B (high ki67) subtype, the proportion of patients with invasive ductal carcinoma was lower in the non-metformin group than in the other two groups (P = 0.001). In both the metformin and non-metformin groups, the proportion of T3/4 patients was higher (P < 0.001), the proportion of patients with lymph node metastasis was higher (P = 0.001), and the proportion of patients with vessel carcinoma embolus was higher (P = 0.001) compared with the nondiabetic group. In conclusion, compared with the metformin group, the non-metformin group had a poorer prognosis for all subtypes of luminal breast cancer. In the diabetic group, only patients with the Luminal B (high ki67) subtype exhibited a poorer prognosis. Therefore, different diabetes medication may have a different impact on the prognosis of different subtypes of luminal breast cancer.

[Prognostic significance of Ki-67 expression before and after neoadjuvant chemotherapy in different biological breast cancer phenotypes].

OBJECTIVE: This study was conducted to analyze the Ki-67 expression before and after neoadjuvant chemotherapy and clinicopathological characteristics of different biological breast cancer phenotypes. The significance and prognostic predictive value of the changes of Ki-67 expression in different biological breast cancer phenotypes were analyzed. METHODS: A regression analysis was performed on 178 patients with invasive breast carcinoma who accepted neoadjuvant chemotherapy at Tianjin Medical University Cancer Institute and Hospital from August 2007 to August 2008. These patients were subtyped by hormone receptor status and HER-2 status. The Ki-67 index (percentage of Ki-67-positive cancer cell nuclei) was determined by immunohistochemistry. The prognostic value of Ki-67 index for disease-free survival (DFS) in different biological breast cancer phenotypes was analyzed using Kaplan-Meier survival and multivariable Cox regression. RESULTS: The overall pathologic CR (pCR) rate, defined as no invasive residuals in the breast and axilla, was 15.2%. The highest pCR rate of 25.0% was observed in the TNBC patients, which was 14.3%, 10.3% and 18.2% in the luminal A, luminal B and HER2 overexpressing patients, respectively (P = 0.040). The changes of Ki-67 expression in pre-NAC and post-NAC patients showed a prognostic significance in luminal A and TNBC (P = 0.019 and P = 0.022, respectively) cases. Clinical stage, the efficacy of NAC, and changes of Ki-67 expression between pre- and post-NAC were independent prognostic factors in TNBC patients who did not achieve pCR. CONCLUSIONS: The Ki-67 expression after neoadjuvant chemotherapy is an independent prognostic factor affecting the disease-free survival (DFS) in TNBC patients who have not achieved pCR.