Lipases are differentially regulated by hormones to maintain free fatty acid homeostasis for insect brain development.

BACKGROUND: Free fatty acids (FFAs) play vital roles as energy sources and substrates in organisms; however, the molecular mechanism regulating the homeostasis of FFA levels in various circumstances, such as feeding and nonfeeding stages, is not fully clarified. Holometabolous insects digest dietary triglycerides (TAGs) during larval feeding stages and degrade stored TAGs in the fat body during metamorphosis after feeding cessation, which presents a suitable model for this study. RESULTS: This study reported that two lipases are differentially regulated by hormones to maintain the homeostasis of FFA levels during the feeding and nonfeeding stages using the lepidopteran insect cotton bollworm Helicoverpa armigera as a model. Lipase member H-A-like (Lha-like), related to human pancreatic lipase (PTL), was abundantly expressed in the midgut during the feeding stage, while the monoacylglycerol lipase ABHD12-like (Abhd12-like), related to human monoacylglycerol lipase (MGL), was abundantly expressed in the fat body during the nonfeeding stage. Lha-like was upregulated by juvenile hormone (JH) via the JH intracellular receptor methoprene-tolerant 1 (MET1), and Abhd12-like was upregulated by 20-hydroxyecdysone (20E) via forkhead box O (FOXO) transcription factor. Knockdown of Lha-like decreased FFA levels in the hemolymph and reduced TAG levels in the fat body. Moreover, lipid droplets (LDs) were small, the brain morphology was abnormal, the size of the brain was small, and the larvae showed the phenotype of delayed pupation, small pupae, and delayed tissue remodeling. Knockdown of Abhd12-like decreased FFA levels in the hemolymph; however, TAG levels increased in the fat body, and LDs remained large. The development of the brain was arrested at the larval stage, and the larvae showed a delayed pupation phenotype and delayed tissue remodeling. CONCLUSIONS: The differential regulation of lipases expression by different hormones determines FFAs homeostasis and different TAG levels in the fat body during the feeding larval growth and nonfeeding stages of metamorphosis in the insect. The homeostasis of FFAs supports insect growth, brain development, and metamorphosis.

Mechanistic insights into diversified photoluminescence behaviours of BF2 complexes of N-benzoyl 2-aminobenzothiazoles.

Many BF2 complexes of heteroaromatics are well known for their dual-state emission (DSE) properties. However, AIE and ACQ effects have also been observed in certain cases. To date, no rational explanations have been proposed for these uncommon photoluminescence (PL) behaviours. The current research prepared four BF2 complexes of N-benzoyl 2-aminobenzothiazoles with diversified photoluminescence (PL) properties as model compounds and utilized quantum chemical calculation tools to address this issue. Theoretical calculations revealed that the electron-donating groups (EDGs) at the para-position of the exocyclic phenyl ring exert significant influence on their ground-state electronic structures and vertical excitation features. Potential energy curve (PEC) analysis showed that the exocyclic phenyl ring and NMe2 could not function as effective rotors due to elevated energy barriers. Only the NPh2 of BFBB-3 could spontaneously rotate ∼60° to induce the formation of an emissive twisted intramolecular charge transfer (TICT) state. The two-channel model involving both vibronic relaxation and S0/S1 surface crossing revealed that the drastic narrowing of the S1/S0 energy gap in the region approaching minimun energy conical intersection (MECI) led to the generation of a dark state in BFBB-1. The small energy barrier to access the dark-state region makes the resulting fast internal conversion a competitive channel for excited-state deactivation. In contrast, the presence of EDGs in BFBB-2 and 4 inhibits this pathway, thereby resulting in intense fluorescence emissions in solution. In addition, crystallographic analysis illustrated that the F atoms perpendicular to the polyheterocycle promoted a slipped face-to-face packing mode and enhanced intermolecular interactions. The efficiencies of their solid-state emissions are mainly affected by the degree of π-π overlaps.

20-hydroxyecdysone reprograms amino acid metabolism to support the metamorphic development of Helicoverpa armigera.

Amino acid metabolism is regulated according to nutrient conditions; however, the mechanism is not fully understood. Using the holometabolous insect cotton bollworm (Helicoverpa armigera) as a model, we report that hemolymph metabolites are greatly changed from the feeding larvae to the wandering larvae and to pupae. Arginine, alpha-ketoglutarate (α-KG), and glutamate (Glu) are identified as marker metabolites of feeding larvae, wandering larvae, and pupae, respectively. Arginine level is decreased by 20-hydroxyecdysone (20E) regulation via repression of argininosuccinate synthetase (Ass) expression and upregulation of arginase (Arg) expression during metamorphosis. α-KG is transformed from Glu by glutamate dehydrogenase (GDH) in larval midgut, which is repressed by 20E. The α-KG is then transformed to Glu by GDH-like in pupal fat body, which is upregulated by 20E. Thus, 20E reprogrammed amino acid metabolism during metamorphosis by regulating gene expression in a stage- and tissue-specific manner to support insect metamorphic development.

Scavenger receptor B2, a type III membrane pattern recognition receptor, senses LPS and activates the IMD pathway in crustaceans.

The immune deficiency (IMD) pathway is critical for elevating host immunity in both insects and crustaceans. The IMD pathway activation in insects is mediated by peptidoglycan recognition proteins, which do not exist in crustaceans, suggesting a previously unidentified mechanism involved in crustacean IMD pathway activation. In this study, we identified a Marsupenaeus japonicus B class type III scavenger receptor, SRB2, as a receptor for activation of the IMD pathway. SRB2 is up-regulated upon bacterial challenge, while its depletion exacerbates bacterial proliferation and shrimp mortality via abolishing the expression of antimicrobial peptides. The extracellular domain of SRB2 recognizes bacterial lipopolysaccharide (LPS), while its C-terminal intracellular region containing a cryptic RHIM-like motif interacts with IMD, and activates the pathway by promoting nuclear translocation of RELISH. Overexpressing shrimp SRB2 in Drosophila melanogaster S2 cells potentiates LPS-induced IMD pathway activation and diptericin expression. These results unveil a previously unrecognized SRB2-IMD axis responsible for antimicrobial peptide induction and restriction of bacterial infection in crustaceans and provide evidence of biological diversity of IMD signaling in animals. A better understanding of the innate immunity of crustaceans will permit the optimization of prevention and treatment strategies against the arising shrimp diseases.

20-Hydroxyecdysone counteracts insulin to promote programmed cell death by modifying phosphoglycerate kinase 1.

BACKGROUND: The regulation of glycolysis and autophagy during feeding and metamorphosis in holometabolous insects is a complex process that is not yet fully understood. Insulin regulates glycolysis during the larval feeding stage, allowing the insects to grow and live. However, during metamorphosis, 20-hydroxyecdysone (20E) takes over and regulates programmed cell death (PCD) in larval tissues, leading to degradation and ultimately enabling the insects to transform into adults. The precise mechanism through which these seemingly contradictory processes are coordinated remains unclear and requires further research. To understand the coordination of glycolysis and autophagy during development, we focused our investigation on the role of 20E and insulin in the regulation of phosphoglycerate kinase 1 (PGK1). We examined the glycolytic substrates and products, PGK1 glycolytic activity, and the posttranslational modification of PGK1 during the development of Helicoverpa armigera from feeding to metamorphosis. RESULTS: Our findings suggest that the coordination of glycolysis and autophagy during holometabolous insect development is regulated by a balance between 20E and insulin signaling pathways. Glycolysis and PGK1 expression levels were decreased during metamorphosis under the regulation of 20E. Insulin promoted glycolysis and cell proliferation via PGK1 phosphorylation, while 20E dephosphorylated PGK1 via phosphatase and tensin homolog (PTEN) to repress glycolysis. The phosphorylation of PGK1 at Y194 by insulin and its subsequent promotion of glycolysis and cell proliferation were important for tissue growth and differentiation during the feeding stage. However, during metamorphosis, the acetylation of PGK1 by 20E was key in initiating PCD. Knockdown of phosphorylated PGK1 by RNA interference (RNAi) at the feeding stage led to glycolysis suppression and small pupae. Insulin via histone deacetylase 3 (HDAC3) deacetylated PGK1, whereas 20E via acetyltransferase arrest-defective protein 1 (ARD1) induced PGK1 acetylation at K386 to stimulate PCD. Knockdown of acetylated-PGK1 by RNAi at the metamorphic stages led to PCD repression and delayed pupation. CONCLUSIONS: The posttranslational modification of PGK1 determines its functions in cell proliferation and PCD. Insulin and 20E counteractively regulate PGK1 phosphorylation and acetylation to give it dual functions in cell proliferation and PCD.

Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion / 中华肿瘤杂志

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

Value of direct immunohistochemical staining in assisting intraoperative frozen diagnosis of bronchiolar adenoma / 中华病理学杂志

Objective: To explore the feasibility and application value of intraoperative direct immunohistochemical (IHC) staining in improving the diagnosis accuracy in difficult cases of bronchiolar adenoma (BA). Methods: Nineteen cases with single or multiple pulmonary ground-glass nodules or solid nodules indicated by imaging in Cancer Hospital of Chinese Academy of Medical Sciences from January to July 2021 and with difficulty in differential diagnosis at frozen HE sections were selected. In the experimental group, direct IHC staining of cytokeratin 5/6 (CK5/6) and p63 was performed on frozen sections to assist the differentiation of BA from in situ/micro-invasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the control group, two pathologists performed routine frozen HE section diagnosis on these 19 cases. The diagnostic results of paraffin sections were used as the gold standard. The sensitivity and specificity of BA diagnosis, consistency with paraffin diagnosis and time used for frozen diagnosis were compared between the experimental group and the control group. Results: The basal cells of BA were highlighted by CK5/6 and p63 staining. There were no basal cells in the in situ/microinvasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the experimental group, the sensitivity and specificity with aid of direct IHC staining for BA were 100% and 86.7%, respectively, and the Kappa value of frozen and paraffin diagnosis was 0.732, and these were significantly higher than those in the control group (P<0.05). The average time consumption in the experimental group (32.4 min) was only 7 min longer than that in the control group (25.4 min). Conclusions: Direct IHC staining can improve the accuracy of BA diagnosis intraoperatively and reduce the risk of misdiagnosis, but require significantly longer time. Thus frozen direct IHC staining should be restricted to cases with difficulty in differentiating benign from malignant diseases, especially when the surgical modalities differ based on the frozen diagnosis.

Expert consensus on PD-L1 expression testing in esophageal carcinoma in China / 中华肿瘤杂志

In recent years, immunotherapy represented by immune checkpoint inhibitors programmed death 1 (PD-1) has made great progress in the treatment of esophageal cancer and is rewriting the global paradigm for the treatment of esophageal cancer. According to current data, only a small number of patients with esophageal cancer could benefit from immunotherapy. Therefore, it is a challenge to screen the potential beneficiaries of PD-1 inhibitors. Studies have shown that the expression level of programmed death-ligand 1 (PD-L1) in esophageal cancer is closely associated with the efficacy of PD-1 inhibitors, and PD-L1 is the most important predictive biomarker of the efficacy of PD-1 inhibitors. With the clinical application of different PD-1 inhibitors and PD-L1 protein expression detection platforms, clarifying the clinical significance and timing of detection of PD-L1 protein expression in esophageal cancer, and establishing a standardized PD-L1 testing procedure, are of great significance to improve the accuracy of detection and reduce the difference between laboratories, so as to maximize the therapeutic benefits for patients. This consensus was finally reached, based on the combination of literature, expert experience, and internal discussion and voting of committee members, to provide an accurate and reliable evidence for clinicians to make decisions.

Effect of Astragalus polysaccharides on the cryopreservation of goat semen.

During cryopreservation, sperm encounters oxidative stress induced by excessive reactive oxygen species (ROS), destroying the sperm plasma membrane structure and reducing its physiological functions. The present study aimed to evaluate the effect of Astragalus polysaccharides (APS) on the cryopreservation of dairy goat semen. Semen was collected from six goats, and then qualified semen with movement >80% was selected after preliminary evaluation. The semen was divided into six aliquots, diluted with dairy goat semen extender (1:10) at 37 °C, containing 0 g/L (control), 0.1 g/L, 0.2 g/L, 0.3 g/L, 0.4 g/L and 0.5 g/L APS, cryopreserved, and stored in liquid nitrogen (-196 °C). Sperm quality was assessed after freeze-thawing. The highest sperm motility, motion performance, plasma membrane integrity, acrosome integrity, and antioxidant properties (total antioxidant capacity and levels of antioxidant enzymes) were recorded (P < 0.05) in the 0.2 g/L APS group after the semen was freeze-thawed. The control and the optimal group (0.2 g/L) were then selected to analyze the effects of APS on sperm energy metabolism (mitochondrial membrane potential [MMP] and adenosine triphosphate [ATP]), sperm apoptosis, and the expression of the AMPK signaling pathway. The results showed that treatment with 0.2 g/L APS increased sperm MMP and ATP content after freeze-thawing, reduced sperm apoptosis by regulating apoptosis-related proteins, and promoted AMPK phosphorylation by activating the AMPK signaling pathway. The cleavage rate of frozen goat sperm during in vitro fertilization (IVF) was also observed to increase. These findings suggest meaningful ways to improve cryopreservation of dairy goat semen and provide new insights into the mechanism by which APS protects sperm from oxidative damage via AMPK activation.

Identification and Functional Analysis of G Protein-Coupled Receptors in 20-Hydroxyecdysone Signaling From the Helicoverpa armigera Genome.

G protein-coupled receptors (GPCRs) are the largest family of membrane receptors in animals and humans, which transmit various signals from the extracellular environment into cells. Studies have reported that several GPCRs transmit the same signal; however, the mechanism is unclear. In the present study, we identified all 122 classical GPCRs from the genome of Helicoverpa armigera, a lepidopteran pest species. Twenty-four GPCRs were identified as upregulated at the metamorphic stage by comparing the transcriptomes of the midgut at the metamorphic and feeding stages. Nine of them were confirmed to be upregulated at the metamorphic stage. RNA interference in larvae revealed the prolactin-releasing peptide receptor (PRRPR), smoothened (SMO), adipokinetic hormone receptor (AKHR), and 5-hydroxytryptamine receptor (HTR) are involved in steroid hormone 20-hydroxyecdysone (20E)-promoted pupation. Frizzled 7 (FZD7) is involved in growth, while tachykinin-like peptides receptor 86C (TKR86C) had no effect on growth and pupation. Via these GPCRs, 20E regulated the expression of different genes, respectively, including Pten (encoding phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase), FoxO (encoding forkhead box O), BrZ7 (encoding broad isoform Z7), Kr-h1 (encoding Krüppel homolog 1), Wnt (encoding Wingless/Integrated) and cMyc, with hormone receptor 3 (HHR3) as their common regulating target. PRRPR was identified as a new 20E cell membrane receptor using a binding assay. These data suggested that 20E, via different GPCRs, regulates different gene expression to integrate growth and development.

The homotetramerization of a GPCR transmits the 20-hydroxyecdysone signal and increases its entry into cells for insect metamorphosis.

Animal steroid hormones initiate signaling by passive diffusion into cells and binding to their nuclear receptors to regulate gene expression. Animal steroid hormones can initiate signaling via G protein-coupled receptors (GPCRs); however, the underlying mechanisms are unclear. Here, we show that a newly discovered ecdysone-responsive GPCR, ErGPCR-3, transmits the steroid hormone 20-hydroxyecdysone (20E) signal by binding 20E and promoting its entry into cells in the lepidopteran insect Helicoverpa armigera Knockdown of ErGPCR-3 in larvae caused delayed and abnormal pupation, inhibited remodeling of the larval midgut and fat body, and repressed 20E-induced gene expression. Also, 20E induced both the interaction of ErGPCR-3 with G proteins and rapid intracellular increase in calcium, cAMP and protein phosphorylation. ErGPCR-3 was endocytosed by GPCR kinase 2-mediated phosphorylation, and interacted with ß-arrestin-1 and clathrin, to terminate 20E signaling under 20E induction. We found that 20E bound to ErGPCR-3 and induced the ErGPCR-3 homodimer to form a homotetramer, which increased 20E entry into cells. Our study revealed that homotetrameric ErGPCR-3 functions as a cell membrane receptor and increases 20E diffusion into cells to transmit the 20E signal and promote metamorphosis.

Juvenile hormone induces methoprene-tolerant 1 phosphorylation to increase interaction with Taiman in Helicoverpa armigera.

Methoprene-tolerant 1 (Met1) is a basic-helix-loop-helix Per/Arnt/Sim (bHLH-PAS) protein identified as the intracellular receptor of juvenile hormone (JH). JH induces phosphorylation of Met1; however, the phosphorylation site and outcomes of phosphorylation are not well characterized. In the present study, using the lepidopteran insect and serious agricultural pest Helicoverpa armigera (cotton bollworm) as a model, we showed that JH III induced threonine-phosphorylation of Met1 at threonine 393 (Thr393) in the Per-Arnt-Sim (PAS) B domain. Thr393-phosphorylation was necessary for Met1 binding to the JH response element (JHRE) to promote the transcription of Kr-h1 (encoding transcription factor Krüppel homolog 1) because Thr393-phosphorylated Met1 increased its interaction with Taiman (Tai) and prevented the Met1-Met1 association. However, JH III could not prevent Met1-Met1 association after Met1-Thr393 was mutated, suggesting that Thr393-phosphorylation is an essential mechanism by which JH prevents Met1-Met1 association. The results showed that JH induces Met1 phosphorylation on Thr393, which prevents Met1-Met1 association, enhances Met1 interaction with Tai, and promotes the binding of Met1-Tai transcription complex to the E-box in the JHRE to regulate Kr-h1 transcription.

Comparison of long-term outcomes between endoscopic submucosal dissection and surgical resection for early gastric cancer with undifferentiated histology / 中华胃肠外科杂志

Objective: Endoscopic submucosal dissection (ESD) of undifferentiated early gastric cancer (UD-EGC) remains controversial due to high positive rate of horizontal and vertical resection margins and the risk of lymph node metastasis. The purpose of this study was to compare long-term outcomes of patients with UD-EGC undergoing ESD versus surgery. Methods: This study was a retrospective cohort study. Inclusion criteria: (1) patients with early gastric cancer undergoing ESD or surgical resection; (2) histological types included poorly differentiated adenocarcinoma, poorly differentiated adenocarcima with signet ring cell carcinoma, and signet ring cell carcinoma; (3) no lymph node metastasis or distant metastasis was confirmed by preoperative CT and endoscopic ultrasonography. Exclusion criteria: (1) previous surgical treatment for gastric cancer; (2) synchronous tumors; (3) death with unknown cause; (4) additional surgical treatment was performed within 1 month after ESD. According to the above criteria, clinical data of patients with UD-EGC who received ESD or surgery treatment in Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2016 were collected. After further comparing the clinical outcomes between the two groups by 1:1 propensity score matching, 61 patients in the ESD group and 61 patients in the surgery group were finally included in this study. The disease-free and overall survivals were analyzed by Kaplan-Meier method. Results: All patients in the two groups completed operations successfully. In the ESD group, the median operation time was 46.3 (26.5, 102.3) minutes, 61 cases (100%) were en-bloc resection, and 57 cases (93.4%) were complete resection. Positive margin was found in 4 (6.6%) patients, of whom 2 were positive in horizontal margin and 2 were positive both in horizontal and vertical margins. In the surgery group, only 1 case had positive horizontal margin and no positive vertical margin was observed. There was no significant difference in the positive rate of margin between the two groups (P>0.05). Median follow-up time was 59.8 (3.0, 131.5) months. The follow-up rate of ESD group and surgery group was 82.0% (50/61) and 95.1% (58/61), respectively. The 5-year disease-free survival rate in ESD group and surgery group was 98.2% and 96.7%, respectively (P=0.641), and the 5-year overall survival rate was 98.2% and 96.6%, respectively (P=0.680). In the ESD group, 1 patient (1.6%) had lymph node recurrence, without local recurrence or distant metastasis. In the surgery group, 1 case (1.6%) had anastomotic recurrence and 1 (1.6%) had distant metastasis. Conclusion: ESD has a sinilar long-term efficacy to surgery in the treatment of UD-EGC.

Clinicopathological and prognostic significance of ERα and ERβ expression in lung carcinomas: a tissue microarray study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of ERα and ERβ in lung carcinomas and investigate their clinicopathological and prognostic significance by using tissue microarray assay and immunohistochemical staining.</p><p><b>METHODS</b>Six hundred and ninety-eight lung cancer specimens were used in this study, including 651 cases of non-small cell lung carcimomas (NSCLCs) and 47 cases of small cell lung cancers (SCLCs). There were 309 cases of adenocarcimoma and 342 cases of squamous cell carcinoma. The expression of ERα and ERβ was analyzed by immunohistochemistry on paraffin-embedded sections.</p><p><b>RESULTS</b>In the normal lung tissues, expression of ERα and ERβ was 0% (0/35) and 25.0% (9/36), respectively. In the tumor tissues, ERα was expressed in 209 of 295 AC cases (70.8%), 169 of 330 SCC cases (51.2%) and 9 of 47 SCLC cases (19.1%) (P < 0.001). ERβ was expressed in 200 of 297 AC cases (67.3%), 140 of 322 SCC cases (43.5%) and 31 of 47 SCLC cases (66.0%) (P < 0.001). In NSCLC, the expression of ERα and ERβ was significantly associated with smoking, stage and lymph node metastasis, also with sex refer to ERβ (P < 0.05), but not significantly with age, tumor size and degree of differentiation (P > 0.05). Follow-up was completed in 398 NSCLC cases, and no significant correlation was found between the prognosis and expression of ERα and ERβ.</p><p><b>CONCLUSIONS</b>The expression of ERα and ERβ has significant difference in lung adenocarcinoma, squamous cell carcinoma and small cell lung cancer. In NSCLC, expression of ERα and ERβ is associated with smoking, stage, and lymph node metastasis. The expression of ERβ is higher in female than in male NSCLC patients.</p>

Application value of sentinel node biopsy in early stage oral tongue cancer with clinically negative neck / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the liability of sentinel node biopsy in the treatment of early stage oral tongue carcinoma with clinically negative neck.</p><p><b>METHODS</b>Eighteen patients with T1 or T2 oral tongue carcinoma were enrolled in the prospective study. Preoperative lymphoscintigraphy and intra-operative hand-held gamma probe techniques were used to detect the sentinel lymph nodes. The sentinel lymph node biopsies were sent to frozen section pathology and the results were compared with specimen of routine selective neck dissection (I ∼ III or I ∼ IV). The accuracy of cervical metastasis prediction was compared between sentinel node biopsy and tumor thickness.</p><p><b>RESULTS</b>Sentinel lymph nodes were identified in all 18 cases. The numbers of sentinel lymph nodes of level Ib, IIa and III were 6, 22 and 2, respectively. In this series, positive sentinel lymph nodes were revealed in 4 cases, which were also positive in the postoperative routine histology.In other cases, both sentinel lymph nodes and routine histology were negative. Both the sensitivity and specificity were 100%. Sentinel lymph node biopsy obviously improved the specificity of predicting cervical metastasis comparing with the tumor thickness. (100% vs. 36.4%).</p><p><b>CONCLUSION</b>Sentinel node biopsy is effective and reliable in the treatment of early stage oral tongue cancer, and deserves clinical application.</p>

Comparative study of endoscopic mucous resection with transparent cap and endoscopic multi-band mucosectomy for early esophageal cancer and precancerous lesion / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of endoscopic mucous resection with transparent cap (EMR-Cap) and endoscopic multi-band mucosectomy (MBM) in the treatment of early esophageal cancer and precancerous lesion.</p><p><b>METHODS</b>A retrospective study was performed to review 30 EMR-Cap cases from December 2008 to December 2009 and 32 MBM cases from January 2010 to January 2011 of early esophageal cancer and precancerous lesions. The differences between these two techniques in efficacy, safety, and cost were compared.</p><p><b>RESULTS</b>In EMR-Cap group, the median resection time was 26(10-56) min and median procedure time was 43(22-81) min, significantly longer than those in MBM group [10(7-18) min and 32(28-45) min, P=0.036 and 0.038, respectively]. There were no significant differences between the two groups in total thickness and depth of resected lesions (P>0.05). In EMR-Cap group, the median cost was significantly higher than that of MBM group [(5466±354) vs. (4014±368) RMB, P=0.008)].</p><p><b>CONCLUSIONS</b>EMR-Cap and MBM are minimally invasive, safe and effective methods in the treatment of early esophageal cancer and precancerous lesions. Compared to the EMR-Cap, MBM is simple with shorter treatment time and lower cost.</p>

Expression and clinical significance of BRCA1 in human esophageal squamous cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of BRCA1 in esophageal squamous cell carcinoma (ESCC) tissues and evaluate its correlation with clinicopathological features as well as the prognosis of ESCC patients.</p><p><b>METHODS</b>The expression of BRCA1 was detected by immunohistochemistry (IHC) in 201 specimens of T3 stage ESCC tissues and corresponding adjacent normal tissues using tissue microarray. The correlation between BRCA1 expression and clinicopathological features of ESCC was determined by chi-square analysis. The cumulative survival rate was analyzed by Kaplan-Meier method.</p><p><b>RESULTS</b>The positive rate of BRCA1 expression in ESCC tissues was significantly higher than that in adjacent normal tissues [88.6% (178/201) vs. 36.8% (74/201), P < 0.001]. There was a significant correlation between the expression of BRCA1 and lymph node metastasis. In the tumors with positive lymph nodes, strong positive expression of BRCA1 was found in 45.0% (49/109), while only 19.6% (18/92) in tumors without lymph node metastasis, showing a significant difference (P < 0.001). A close relationship was also found between the expression of BRCA1 and gross typing of tumors (P < 0.05). The expression of BRCA1 was not significantly correlated with gender, age, tumor location, differentiation, and tumor thrombus (P > 0.05). The results of Kaplan-Meier analysis indicated that ESCC patients with a higher positive rate of BRCA1 expression have a poorer prognosis (P < 0.05).</p><p><b>CONCLUSIONS</b>The expression of BRCA1 is related to the occurrence and development of esophageal carcinoma. BRCA1 protein may serve as a new potential biomarker in estimating the biological behavior of ESCC.</p>

Efficacy of peripheral blood stem cell transplantation versus conventional chemotherapy on anaplastic large-cell lymphoma:a retrospective study of 64 patients from a single center / 癌症

Anaplastic large-cell lymphoma (ALCL) is characterized by frequently presenting adverse factors at diagnosis. Many groups believed aggressive treatment strategies such as autologous stem cell transplantation brought survival benefit for ALCL patients. However, few compared these approaches with conventional chemotherapy to validate their superiority. Here, we report a study comparing the efficacy of peripheral blood stem cell transplantation (PBSCT) and conventional chemotherapy on ALCL. A total of 64 patients with primary systemic ALCL were studied retrospectively. The median follow-up period was 51 months (range, 1-167 months). For 48 patients undergoing conventional chemotherapy only, the 4-year event-free survival (EFS) and overall survival (OS) rates were 70.7% and 88.3%, respectively. Altogether, 16 patients underwent PBSCT, including 11 at first remission (CR1/PR1), 3 at second remission, and 2 with disease progression during first-line chemotherapy. The 4-year EFS and OS rates for patients underwent PBSCT at first remission were 81.8% and 90.9%, respectively. Compared with conventional chemotherapy, PBSCT did not show superiority either in EFS (P = 0.240) or in OS (P = 0.580) when applied at first remission. Univariate analysis showed that patients with B symptoms (P = 0.001), stage III/IV disease (P = 0.008), bulky disease (P = 0.075), negative anaplastic lymphoma kinase (ALK) expression (P = 0.059), and age ≤ 60 years (P = 0.054) had lower EFS. Furthermore, PBSCT significantly improved EFS in patients with B symptoms (100% vs. 50.8%, P = 0.027) or bulky disease (100% vs. 52.8%, P = 0.045) when applied as an up-front strategy. Based on these results, we conclude that, for patients with specific adverse factors such as B symptoms and bulky disease, PBSCT was superior to conventional chemotherapy in terms of EFS.

Primary superficial small cell neuroendocrine carcinoma of esophagus: clinicopathologic and immunohistochemical analysis of 15 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic and immunohistochemical features of primary superficial esophageal small cell neuroendocrine carcinoma (ESCNC).</p><p><b>METHODS</b>The clinical, pathologic and immunohistochemical features were retrospectively analyzed in 15 cases of superficial ESCNC. An immunohistochemical study for chromogranin A, neuron-specific enolase, synaptophysin, CD56, TTF-1, 34βE12, AE1/AE3, and CK10/13 was performed.</p><p><b>RESULTS</b>Superficial ESCNC accounted for 4.8%(15/312) of all cases of superficial carcinoma of the esophagus encountered during the same period. The median survival time was 19 months and the mean survival time was 23.7 months after diagnosis. The one, two and five-year survival rates were 10/15, 5/15 and 1/15, respectively. The immunophenotypic profile was as follows: neuron-specific enolase (15/15), synaptophysin (15/15), AE1/AE3 (15/15), CD56 (14/15), TTF-1 (9/15), chromogranin A (8/15), 34βE12 (1/15) and CK10/13 (0/15).</p><p><b>CONCLUSIONS</b>Superficial ESCNC is a rare and aggressive malignant tumor with poor prognosis. Surgical resection coupled with post-operative chemoradiotherapy is the mainstay of treatment. The immunohistochemical study is valuable in pathologic diagnosis and differential diagnosis.</p>

Expressions of the γ2 chain of laminin-5 and secreted protein acidic and rich in cysteine in esophageal squamous cell carcinoma and their relation to prognosis / 癌症

Previous studies have shown that the expressions of the γ2 chain of laminin-5 and secreted protein acidic and rich in cysteine (SPARC) play important roles in oncogenesis and the development of carcinoma. To assess the expressions of laminin-5 γ2 chain and SPARC in esophageal squamous cell carcinoma (SCC), and to clarify the prognostic significance of the expressions of laminin-5 γ2 chain and SPARC in esophageal SCC, we detected the expressions of laminin-5 γ2 chain and SPARC in cancer tissue and corresponding normal mucosa from 116 patients with advanced (stages II-IV) esophageal SCC using the tissue microarray-based immunohistochemistry and analyzed the correlation of the expressions with clinicopathologic characteristics and survival. We found that in normal esophageal tissues, laminin-5 γ2 chain was expressed in the basement membrane, whereas in esophageal SCC tissues, laminin-5 γ2 chain was expressed in the cytoplasm of carcinoma cells, with a positive rate of 72.4%. SPARC was not detected in normal esophageal mucosa, but was expressed in stromal fibroblasts in 84.6% of esophageal SCC cases and in cancer cells in 7.8% of esophageal SCC cases. There was a significant correlation between laminin-5 γ2 chain and stromal SPARC expression in esophageal SCC (Spearman's rho=0.423, P<0.001). The expressions of both laminin-5 γ2 chain and stromal SPARC were correlated with survival (P=0.032 and P=0.034, respectively). In stage-II esophageal SCC, the expression of laminin-5 γ2 chain was significantly correlated with survival (P=0.023), while the expression of SPARC was not significantly correlated with survival (P=0.154). Patients with elevated levels of laminin-5 γ2 chain and SPARC expressions had a poorer prognosis than did those lacking elevated levels of laminin-5 γ2 chain expression and/or elevated levels of SPARC expression (P=0.001). In stage-II esophageal SCC, patients with elevated levels of laminin-5 γ2 chain and SPARC expressions had a poorer prognosis (P<0.001). These results suggest that laminin-5 γ2 chain and SPARC may play roles in the progression of esophageal SCC and their simultaneous expression is correlated with poorer prognosis, especially in patients with stage-II SCC.