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Introduction: The role of the Ki-67 Proliferative Index (PI) in the molecular classification and as a predictive and prognostic biomarker in breast cancer is definitive. To address the inconsistency in Ki-67 interpretation and scoring, the International Ki-67 in Breast Cancer Working Group (IKWG) introduced the visual scoring Android Application (APP) and proposed a standardised scoring method. Aim: To determine Ki-67 proliferative indices by both the Global Method (GW) with the Ki-67 visual scoring app recommended by IKWG and conventional institutional Hotspot Method (HM), and to analyse the agreement between the indices obtained by these two methods. Materials and Methods: A cross-sectional study involving 71 Ki-67 immunostained hormone receptor-positive trucut biopsies of breast cancers from January 2022 to January 2024 were retrospectively collected. Two observers independently scored the biopsies using HM and GW by an app in the Department of Pathology of a tertiary care centre. The GW scores of Ki-67 PI obtained were categorised into low, intermediate and high groups based on 2015 St. Gallen guidelines. A two-way random Intraclass Correlation Coefficient (ICC) was used to assess the absolute agreement between two scorers. Results: The overall intraclass correlation between interobserver values by HM was 0.819 (good), while it was 0.971 (excellent) by GW. The overall interobserver mean difference was five times greater (p-value=0.008, statistically significant) than the overall interobserver global weighted scores (p-value=0.901, not statistically significant). Conclusion: The study highlighted the significant interobserver variability in HM compared to GW scores by the app. The standardised app scoring method has the potential to broaden the prognostic role of Ki-67 as a companion diagnostic tool.

In the present study, the debatable prognostic value of Ki67 in patients with non‐small cell lung cancer (NSCLC) was attributed to the heterogeneity between lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). Based on meta‐analyses of 29 studies, a retrospective immunohistochemical cohort of 1479 patients from our center, eight transcriptional datasets and a single‐cell datasets with 40 patients, we found that high Ki67 expression suggests a poor outcome in LUAD, but conversely, low Ki67 expression indicates worse prognosis in LUSC. Furthermore, low proliferation in LUSC is associated with higher metastatic capacity, which is related to the stronger epithelial‐mesenchymal transition potential, immunosuppressive microenvironment and angiogenesis. Finally, nomogram model incorporating clinical risk factors and Ki67 expression outperformed the basic clinical model for the accurate prognostic prediction of LUSC. With the largest prognostic assessment of Ki67 from protein to mRNA level, our study highlights that Ki67 also has an important prognostic value in NSCLC, but separate evaluation of LUAD and LUSC is necessary to provide more valuable information for clinical decision‐making in NSCLC. [ABSTRACT FROM AUTHOR]

Background: The pentose phosphate pathway (PPP) is an important mechanism by which tumour cells resist stressful environments and maintain malignant proliferation. However, the mechanism by which the PPP regulates these processes in colorectal cancer (CRC) remains elusive. Methods: Closely related PPP genes were obtained from the TCGA and GEO databases. The effect of ATP13A2 on CRC cell proliferation was evaluated by performing in vitro assays. The connection between the PPP and ATP13A2 was explored by assessing proliferation and antioxidative stress. The molecular mechanism by which ATP13A2 regulates the PPP was investigated using chromatin immunoprecipitation and dual luciferase experiments. The clinical therapeutic potential of ATP13A2 was explored using patient‐derived xenograft (PDX), patient‐derived organoid (PDO) and AOM/DSS models. Findings: We identified ATP13A2 as a novel PPP‐related gene. ATP13A2 deficiency inhibited CRC growth and PPP activity, as manifested by a decrease in the levels of PPP products and an increase in reactive oxygen species levels, whereas ATP13A2 overexpression induced the opposite effect. Mechanistically, ATP13A2 regulated the PPP mainly by affecting phosphogluconate dehydrogenase (PGD) mRNA expression. Subsequent studies showed that ATP13A2 overexpression promoted TFEB nuclear localization by inhibiting the phosphorylation of TFEB, thereby enhancing the transcription of PGD and ultimately affecting the activity of the PPP. Finally, ATP13A2 knockdown inhibited CRC growth in PDO and PDX models. ATP13A2−/− mice had a lower CRC growth capacity than ATP13A2+/+ in the AOM/DSS model.Our findings revealed that ATP13A2 overexpression‐driven dephosphorylation of TFEB promotes PPP activation by increasing PGD transcription, suggesting that ATP13A2 may serve as a potential target for CRC therapy. [ABSTRACT FROM AUTHOR]

Abstract Background The pentose phosphate pathway (PPP) is an important mechanism by which tumour cells resist stressful environments and maintain malignant proliferation. However, the mechanism by which the PPP regulates these processes in colorectal cancer (CRC) remains elusive. Methods Closely related PPP genes were obtained from the TCGA and GEO databases. The effect of ATP13A2 on CRC cell proliferation was evaluated by performing in vitro assays. The connection between the PPP and ATP13A2 was explored by assessing proliferation and antioxidative stress. The molecular mechanism by which ATP13A2 regulates the PPP was investigated using chromatin immunoprecipitation and dual luciferase experiments. The clinical therapeutic potential of ATP13A2 was explored using patient‐derived xenograft (PDX), patient‐derived organoid (PDO) and AOM/DSS models. Findings We identified ATP13A2 as a novel PPP‐related gene. ATP13A2 deficiency inhibited CRC growth and PPP activity, as manifested by a decrease in the levels of PPP products and an increase in reactive oxygen species levels, whereas ATP13A2 overexpression induced the opposite effect. Mechanistically, ATP13A2 regulated the PPP mainly by affecting phosphogluconate dehydrogenase (PGD) mRNA expression. Subsequent studies showed that ATP13A2 overexpression promoted TFEB nuclear localization by inhibiting the phosphorylation of TFEB, thereby enhancing the transcription of PGD and ultimately affecting the activity of the PPP. Finally, ATP13A2 knockdown inhibited CRC growth in PDO and PDX models. ATP13A2−/− mice had a lower CRC growth capacity than ATP13A2+/+ in the AOM/DSS model.Our findings revealed that ATP13A2 overexpression‐driven dephosphorylation of TFEB promotes PPP activation by increasing PGD transcription, suggesting that ATP13A2 may serve as a potential target for CRC therapy.

High glucose (HG), a hallmark of the tumour microenvironment, is also a biomechanical stressor, as it exerts hyper-osmotic stress (HG-HO), but not much is known regarding how tumour cells mechanoadapt to HG-HO. Therefore, this study aimed to delineate the novel molecular mechanisms by which tumour cells mechanoadapt to HG/HG-HO and whether phytochemical-based interference in these mechanisms can generate tumour-cell-selective vulnerability to cell death. Mannitol and L-glucose were used as hyper-osmotic equivalents of high glucose. The results revealed that the tumour cells can efficiently mechanoadapt to HG-HO only in the normoxic microenvironment. Under normoxic HG/HG-HO stress, tumour cells polySUMOylate a higher pool of mitotic driver pH3(Ser10), which translocates to the nucleus and promotes faster cell divisions. On the contrary, acute hypoxia dampens HG/HG-HO-associated excessive proliferation by upregulating sentrin protease SENP7. SENP7 promotes abnormal SUMOylation of pH3(Ser10), thereby restricting its nuclear entry and promoting the M-phase arrest and cell loss. However, the hypoxia-arrested cells that managed to survive showed relapse upon reversal to normoxia as well as upregulation of pro-survival-associated SENP1, and players in tumour growth signalling, autophagy, glycolytic pathways etc. Depletion of SENP1 in both normoxia and hypoxia caused significant loss of tumour cells vs undepleted controls. SENP1 was ascertained to restrict the abnormal SUMOylation of pH3(Ser10) in both normoxia and hypoxia, although not so efficiently in hypoxia, due to the opposing activity of SENP7. Co-treatment with Momordin Ic (MC), a natural SENP1 inhibitor, and Gallic Acid (GA), an inhibitor of identified major pro-tumourigenic signalling (both enriched in Momordica charantia), eliminated surviving tumour cells in normal glucose, HG and HG-HO normoxic and hypoxic microenvironments, suggesting that appropriate and enhanced polySUMOylation of pH3(Ser10) in response to HG/HG-HO stress was attenuated by this treatment along with further dampening of other key tumourigenic signalling, due to which tumour cells could no longer proliferate and grow. [ABSTRACT FROM AUTHOR]

High glucose (HG), a hallmark of the tumour microenvironment, is also a biomechanical stressor, as it exerts hyper-osmotic stress (HG-HO), but not much is known regarding how tumour cells mechanoadapt to HG-HO. Therefore, this study aimed to delineate the novel molecular mechanisms by which tumour cells mechanoadapt to HG/HG-HO and whether phytochemical-based interference in these mechanisms can generate tumour-cell-selective vulnerability to cell death. Mannitol and L-glucose were used as hyper-osmotic equivalents of high glucose. The results revealed that the tumour cells can efficiently mechanoadapt to HG-HO only in the normoxic microenvironment. Under normoxic HG/HG-HO stress, tumour cells polySUMOylate a higher pool of mitotic driver pH3(Ser10), which translocates to the nucleus and promotes faster cell divisions. On the contrary, acute hypoxia dampens HG/HG-HO-associated excessive proliferation by upregulating sentrin protease SENP7. SENP7 promotes abnormal SUMOylation of pH3(Ser10), thereby restricting its nuclear entry and promoting the M-phase arrest and cell loss. However, the hypoxia-arrested cells that managed to survive showed relapse upon reversal to normoxia as well as upregulation of pro-survival-associated SENP1, and players in tumour growth signalling, autophagy, glycolytic pathways etc. Depletion of SENP1 in both normoxia and hypoxia caused significant loss of tumour cells vs undepleted controls. SENP1 was ascertained to restrict the abnormal SUMOylation of pH3(Ser10) in both normoxia and hypoxia, although not so efficiently in hypoxia, due to the opposing activity of SENP7. Co-treatment with Momordin Ic (MC), a natural SENP1 inhibitor, and Gallic Acid (GA), an inhibitor of identified major pro-tumourigenic signalling (both enriched in Momordica charantia), eliminated surviving tumour cells in normal glucose, HG and HG-HO normoxic and hypoxic microenvironments, suggesting that appropriate and enhanced polySUMOylation of pH3(Ser10) in response to HG/HG-HO stress was attenuated by this treatment along with further dampening of other key tumourigenic signalling, due to which tumour cells could no longer proliferate and grow.

Background: Tumour growth and development are dependent on many factors including long noncoding RNAs (lncRNAs). However, limited information is available on the involvement of lncRNAs in non-small cell lung cancer (NSCLC) and the molecular mechanisms have not been defined. Here, we examined the expression of small nucleolar RNA host gene 3 (SNHG3) and its contribution to the development of NSCLC. Methods: We detected SNHG3, miR-216a, and ZEB1 expression in tissues from NSCLC patients and lung adenocarcinoma cell lines using quantitative real-time polymerase chain reaction. Proliferation, migrations, invasion, and apoptosis of tumour cells were assessed using cell counting kit-8, transwell experiments, and flow cytometry after SNHG3 knockdown by small interfering RNAs. Bioinformatics and luciferase reporter assays were employed for analysing the interactions between SNHG3, miR-216a, and ZEB1. Results: We found highly upregulated SNHG3 in tissues and cells from NSCLC patients, which was linked to poor prognosis. SNHG3 silencing diminished the ability of NSCLC cells to proliferate, migrate, and invade and promoted apoptosis. Furthermore, SNHG3 competed with endogenous RNA and enhanced the expression of ZEB1 by interfering with miR-216a. ZEB1 overexpression or miR-216a blockade reversed SNHG3-induced tumour inhibition. Similar effects were observed in vivo where SNHG3 knockdown inhibited NSCLC tumour growth by reducing expression of miR-216a while increasing that of ZEB1. Conclusion: Knockdown of SNHG3 inhibits NSCLC tumour development and progression by upregulation of ZEB1 and interference with miR-216a, revealing an attractive alternative target for patients with NSCLC. [ABSTRACT FROM AUTHOR]

Background: The incidence of Cholangiocellular Carcinoma (CCA) is increasing in the western world. The tumour has a high proportion of desmoplastic stroma and is correlated with a worse prognosis when cancer associated myofibroblasts (CAFs) are present. Recent studies showed promising results after liver transplantation (LTx) in non-resectable early stage CCA. Mycophenolic acid (MPA) and the mTor inhibitor Everolimus are used to prevent organ rejection but recently were shown to exhibit an antiproliferative effect on CCA-cells. Little is known about the influence of immunosuppressive drugs on tumour cell proliferation and migration after paracrine stimulation by CAFs. Moreover, it is still unknown, which signaling pathways are activated following these specific cell-cell interactions.Methods: CCA cell lines HuCCT1 and TFK1 were utilized for the study. CAFs were derived from resected CCA cancer tissue. Cell viability was measured by the crystal violet assay and tumour cell invasion was quantified using a modified co-culture transmigration assay. Semiquantitative cytokine-expression was measured using a cytokine-array. Protein expression and phosphorylation of ERK, STAT3 and AKT was determined by Western-blot analysis.Results: CCA cells treated with MPA exhibited a dose related decrease in cell viability in contrast to Cyclosporine A (CSA) treatment which had no effect on cell viability. Everolimus significantly inhibited proliferation at very low concentrations. The pro-invasive effect of CAFs in co-culture transmigration assay was significantly reduced by Everolimus at a concentration of 1nM (p = 0.047). In contrast, MPA and CSA showed no effect on tumour cell invasion. Treatment of CAFs with 1nM Everolimus showed a significant reduction in the expression of IL 8, IL 13, MCP1, MIF and Serpin E1. CCA-cells showed significant increases in phosphorylation of ERK, STAT3 and AKT under the influence of conditioned CAF-media. This effect was suppressed by Everolimus.Conclusions: The secretion of proinflammatory cytokines by CAFs may lead to increased activation of JAK/STAT3-, ERK- and AKT-signaling and increased migration of CCA-cells. Everolimus abrogates this effect and inhibits proliferation of CCA-cells even at low concentrations. LTx for non-resectable early stage CCA is currently performed in several clinical studies. Consistent with a role for common immunosuppressants in inhibiting tumour cell-proliferation and -invasion, our study indicates that a combination of standard therapies with Everolimus and MPA is a promising therapy option to treat CCA following LTx. [ABSTRACT FROM AUTHOR]

Protein-tyrosine phosphatase SHP2 is encoded by the gene PTPN11. SHP2 is hypothesized to have a critical role in cancer, via the activation of mutations that have been detected in several types of leukaemia and in certain solid tumours, including liver, breast, gastric and cervical cancer. However, to the best of our knowledge, there have been no previous reports evaluating the significance of SHP2 expression in thyroid cancer. The present study evaluated SHP2 expression in 65 thyroid cancer specimens, 40 specimens of self-matched adjacent peritumour tissues and 40 specimens of normal thyroid tissue, using immunohistochemical and western blot analyses with an anti-SHP2 antibody. Western blotting was also used to assess SHP2 expression in thyroid cancer cell lines (SW579, IHH-4, FTC-133, TPC-1, DRO, TA-K, and ML-1) and Nthy-ori3-1 normal thyroid cells. In addition, SHP2 antisense oligonucleotides were used to block SHP2 expression in SW579 cells, and growth inhibition assays were conducted. Increased SHP2 expression was detected in the tumour tissues compared with that of the normal thyroid tissues (P<0.05). SHP2 expression was significantly correlated with poor tumour differentiation (P<0.05), late TNM stage (P<0.05) and lymph node metastasis (P<0.05), suggesting that SHP2 may represent a potential target for thyroid cancer therapy. [ABSTRACT FROM AUTHOR]

In this paper a discrete planar model of the tumour growth is presented. The model is based on hybrid cellular automaton and describes the tumour in a homogeneous tissue. The tissue consists of healthy cells and can have irregular vasculature. The model simulates proliferation processes and necrotic cells appearance which depends on the oxygen supply. There exists a stable solution, which may be used as an approximation of the tissue. Described HCA model can be extended with angiogenesis, nutrients and factors fields. [ABSTRACT FROM AUTHOR]

Multi-drug resistance (MDR) to chemotherapy is the major challenge in the treatment of cancer. MDR can develop by numerous mechanisms including decreased drug uptake, increased drug efflux and the failure to undergo drug-induced apoptosis. Evasion of drug-induced apoptosis through modulation of ion transporters is the main focus of this paper and we demonstrate how pro-apoptotic ion channels are downregulated, while anti-apoptotic ion transporters are upregulated in MDR. We also discuss whether upregulation of ion transport proteins that are important for proliferation contribute to MDR. Finally, we discuss the possibility that the development of MDR involves sequential and localized upregulation of ion channels involved in proliferation and migration and a concomitant global and persistent downregulation of ion channels involved in apoptosis. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to assess the potential usefulness of 3-deoxy-3-F-fluorothymidine (FLT) as a radiopharmaceutical for imaging the early therapeutic effects of docetaxel (DTX) on tumour proliferation in hormone-refractory prostate cancer (HRPC). Methods: Cells of the androgen-independent human prostate tumour cell line, 22Rv1, were implanted in athymic male mice. Approximately 3 weeks after cell implantation, the mice were treated with DTX or vehicle. Before and after the treatment, the mice were imaged with a microPET-Focus-F120 scanner (Concorde Microsystems, Knoxville, TN, USA) using FLT and F-fluorodeoxyglucose (FDG). Tracer accumulations in the tumours were then analysed and compared with the proliferation activity and apoptotic index of the tumours. In a separate cell study, 22Rv1 cells were treated with DTX, then incubated with FLT or FDG and examined for their tracer uptake. Results: The microPET imaging showed a significant decrease of FLT uptake in tumours after administration of DTX, while the changes of FDG uptake were minimal. Immunohistochemical analysis of the tumours revealed that the changes of FLT uptake were well correlated with those of proliferation activity but not with the apoptotic index. In vitro studies demonstrated that the significant decrease of FLT uptake in the cells after incubation with DTX correlated with the % S-phase cell fraction, while there were only minimal changes in the prostate-specific antigen concentration of the cell medium and FDG uptake in the cells. Conclusion: These results indicate that FLT is a promising tracer for monitoring the early effects of anticancer therapy with DTX in patients with HRPC. [ABSTRACT FROM AUTHOR]

The nucleoside analogue 3′-deoxy-3′-18F-fluorothymidine (FLT) has recently been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively evaluated whether FLT uptake reflects proliferative activity as indicated by the Ki-67 index in non-small cell lung cancer (NSCLC), in comparison with 2-deoxy-2-18F-fluoro- D-glucose (FDG). A total of 18 patients with newly diagnosed NSCLC were examined with both FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. Tumour lesions were identified as areas of focally increased uptake, exceeding background uptake in the lungs. For semi-quantitative analysis, the maximum standardised uptake value (SUV) was calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with SUVs. The sensitivity of FLT and FDG PET for the detection of lung cancer was 72% and 89%, respectively. Four of the five false-negative FLT PET findings occurred in bronchiolo-alveolar carcinoma. The mean FLT SUV was significantly lower than the mean FDG SUV. A significant correlation was observed between FLT SUV and Ki-67 index ( r = 0.77; p < 0.0002) and for FDG SUV ( r = 0.81; p < 0.0001). The results of this preliminary study suggest that, compared with FDG, FLT may be less sensitive for primary staging in patients with NSCLC. Although FLT uptake correlated significantly with proliferative activity in NSCLC, the correlation was not better than that for FDG uptake. [ABSTRACT FROM AUTHOR]

The oestrogen-responsive gene, EBAG9, whose product is identical to the cancer cell surface antigen RCAS1, is reported to be associated with tumour progression and invasiveness in various carcinomas. In this study, we examined the expression of EBAG9/RCAS1 in hepatocellular carcinoma (HCC), with special reference to its relationship with the stepwise evolution of HCC. Expression was examined by immunohistochemistry and western blotting analysis in 143 HCCs, as well as in non-cancerous liver tissues. After which, the association between enhanced EBAG9/RCAS1 expression and various clinicopathological parameters including Ki-67 labelling index (LI), a marker of proliferative activity, was evaluated. There was a constant low level of EBAG9/RCAS1 expression in non-cancerous liver tissues, with a regular cytoplasmic distribution. Positive immunoreactivity for EBAG9/RCAS1 was detected on the surface and in the cytoplasm of 84 HCC tumours, with an irregular staining pattern. Enhanced EBAG9/RCAS1 expression was correlated with a lower degree of differentiation and Ki-67 LI. Interestingly, expression was enhanced specifically in the less differentiated lesions within ‘nodule-in-nodule’ tumours. In conclusion, EBAG9/RCAS1 was associated with HCC tumour dedifferentiation and increased proliferative activity. Its exact functional role remains to be established. [Copyright &y& Elsevier]

To study the mechanism(s) underlying the proliferation of heterogeneous cell populations within a solid tumour, the NBT-II rat bladder carcinoma system was used. It has been first investigated whether the different cell populations are coupled through gap junctions (GJIC). Cells overexpressing the Cx43 were generated to test for any tumour suppressive activity in vivo. To determine whether GJIC is essential for tumour proliferation and the establishment of a cooperative community effect, NBT-II cells that are incompetent for cell coupling were generated. The data report that (i) carcinoma cells expressing or not FGF-1 are coupled through GJIC in vitro and in coculture and express the gap junction protein Cx43, (ii) overexpression of Cx43 in these cells does not affect their in vitro coupling capacities and in vivo tumourigenic growth properties, (iii) inhibition of GJIC through antisense strategy has no in vivo obvious consequence on the tumour growth properties of the carcinoma, and (iv) the community effect between two carcinoma cell populations does not critically involve cell coupling through gap junctions. [Copyright &y& Elsevier]

Basic fibroblast growth factor (FGF-2) is one of the mitogens that facilitate epithelial proliferation and angiogenesis. We analysed the expression of FGF-2 and type I fibroblast growth factor receptor (FGFR1) in 20 selected cases of human pancreatic carcinoma (PC) in connection with proliferation of tumour cells and intratumour endothelial cells (ECs), using immunohistochemistry and in situ hybridization (ISH). By FGF-2 immunostaining, tumour cells were strongly positive in 10 cases (50%). By FGFR1 immunostaining, stromal fibroblasts and ECs occasionally showed positive staining. Tumour cells in 12 cases (60%) were strongly positive. Expression of FGF-2 mRNA, as examined by ISH, was detected in 12 cases (60%) of PC, and its distribution pattern was similar to that of FGF-2 immunostaining. We divided these cases into two groups according to the result of FGF-2 immunostaining, and examined the Ki67 labelling indices of tumour cells and ECs between these two groups. These two proliferative indices were significantly higher in FGF-2-positive than in FGF-2-negative cases (P<0.05, P<0.05, respectively). These findings suggest that the expression of FGF-2 in PC is strongly associated with the proliferation of tumour cells and ECs and its increased expression may give tumour a growth advantage. [ABSTRACT FROM AUTHOR]

One hundred and fourty-nine axillary lymph node metastases of 35 female patients with invasive breast carcinomas were investigated immunohistochemically for their estrogen receptor (ER)-status. In addition, proliferative activity of the metastatic deposits was determined with the monoclonal antibody Ki-67. Twenty-four primary tumours were ER+ and 11 ER−. Lymph node metastases were ER+ in 21 of the 24 cases where the primary tumour was ER+. In 10 of the 11 cases with ER− primary tumours, the metastases were also ER−. In any given case, the lymph node metastases proved to be either all ER+ or all ER−. Negative ER-status was found to be related to higher numbers of axillary node metastases and higher maximum proliferative activity of the metastatic tumours. Follow-up at 2 years after diagnosis revealed a significantly lower incidence of distant metastases in patients with ER+ primary tumours. [ABSTRACT FROM AUTHOR]

• This research used black tea and green tea, which were processed from the same species of fresh leaves by different processing techniques. • Both black tea and green tea showed the apoptosis in HepG2 cells. Green tea was stronger than black tea in cell apoptosis induction. • Black tea and green tea induced cell apoptosis through PI3K/Akt, and inhibited cell migration and invasion through MMPs signaling pathway. Black tea and green tea were produced via different processing techniques from the same tea leave variety. Then, biochemical components of the two water extracts were analysed to study cell apoptosis, migration and invasion of HepG2 cells induced by black tea and green tea. The monomer components of the black tea and green tea extracts were analysed by colorimetry and HPLC, with MTT assay and colony formation assays used to assess cell proliferation and viability. The effects of black tea and green tea on apoptosis of HepG2 cells were verified by flow cytometry, with wound healing and Transwell experiments used to detect cell invasion and metastasis. The expression of PI3K/Akt signalling and apoptosis-related proteins as well as epithelial-mesenchymal transition (EMT) regulatory factor in HepG2 cells were determined by western blotting after black tea and green tea treatment. Black tea and green tea extracts demonstrated different degrees of inhibition of cell migration and invasion, with green tea inducing more HepG2 cell apoptosis. In addition, green tea and black tea extracts inhibited the growth of HepG2 cells and induced apoptosis via PI3K/Akt, and inhibited cell migration and invasion through the MMPs signalling pathway. This study revealed the effects of fermented (black tea) and non-fermented tea (green tea) on liver cancer cells, providing a basis for the investigation of tea extracts for their anti-tumour potential. [ABSTRACT FROM AUTHOR]

Protein-tyrosine phosphatase SHP2 is encoded by the gene PTPN11. SHP2 is hypothesized to have a critical role in cancer, via the activation of mutations that have been detected in several types of leukaemia and in certain solid tumours, including liver, breast, gastric and cervical cancer. However, to the best of our knowledge, there have been no previous reports evaluating the significance of SHP2 expression in thyroid cancer. The present study evaluated SHP2 expression in 65 thyroid cancer specimens, 40 specimens of self-matched adjacent peritumour tissues and 40 specimens of normal thyroid tissue, using immunohistochemical and western blot analyses with an anti-SHP2 antibody. Western blotting was also used to assess SHP2 expression in thyroid cancer cell lines (SW579, IHH-4, FTC-133, TPC-1, DRO, TA-K, and ML-1) and Nthy-ori3-1 normal thyroid cells. In addition, SHP2 antisense oligonucleotides were used to block SHP2 expression in SW579 cells, and growth inhibition assays were conducted. Increased SHP2 expression was detected in the tumour tissues compared with that of the normal thyroid tissues (P<0.05). SHP2 expression was significantly correlated with poor tumour differentiation (P<0.05), late TNM stage (P<0.05) and lymph node metastasis (P<0.05), suggesting that SHP2 may represent a potential target for thyroid cancer therapy.