Potential Benefits of Green Tea in Prostate Cancer Prevention and Treatment: A Comprehensive Review.

Prostate cancer is a prevalent and debilitating disease that necessitates effective prevention and treatment strategies. Green tea, a well-known beverage derived from the Camellia sinensis plant, contains bioactive compounds with potential health benefits, including catechins and polyphenols. This comprehensive review aims to explore the potential benefits of green tea in prostate cancer prevention and treatment by examining existing literature. Green tea possesses antioxidant, anti-inflammatory, and anti-carcinogenic properties attributed to its catechins, particularly epigallocatechin gallate. Epidemiological studies have reported an inverse association between green tea consumption and prostate cancer risk, with potential protection against aggressive forms of the disease. Laboratory studies demonstrate that green tea components inhibit tumor growth, induce apoptosis, and modulate signaling pathways critical to prostate cancer development and progression. Clinical trials and human studies further support the potential benefits of green tea. Green tea consumption has been found to be associated with a reduction in prostate-specific antigen levels, tumor markers, and played a potential role in slowing disease progression. However, challenges remain, including optimal dosage determination, formulation standardization, and conducting large-scale, long-term clinical trials. The review suggests future research should focus on combinatorial approaches with conventional therapies and personalized medicine strategies to identify patient subgroups most likely to benefit from green tea interventions.

Small molecule inhibitors targeting the cancers.

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer. Due to their advantages in a wide range of targets, convenient medication, and the ability to penetrate into the central nervous system, many efforts have been devoted to developing more small molecule inhibitors. To date, 88 small molecule inhibitors have been approved by the United States Food and Drug Administration to treat cancers. Despite remarkable progress, small molecule inhibitors in cancer treatment still face many obstacles, such as low response rate, short duration of response, toxicity, biomarkers, and resistance. To better promote the development of small molecule inhibitors targeting cancers, we comprehensively reviewed small molecule inhibitors involved in all the approved agents and pivotal drug candidates in clinical trials arranged by the signaling pathways and the classification of small molecule inhibitors. We discussed lessons learned from the development of these agents, the proper strategies to overcome resistance arising from different mechanisms, and combination therapies concerned with small molecule inhibitors. Through our review, we hoped to provide insights and perspectives for the research and development of small molecule inhibitors in cancer treatment.

[Measurement of the mesiobuccal root canal width and taper of maxillary first molars].

PURPUSE: To measure the root canal morphology of the maxillary first molars, to provide reference for clinical work. METHODS: Fifty maxillary first molars were collected and the mesiobuccal root canal taper was observed through production of transparent tooth. The mesiobuccal roots were dissected transversely from their apical foramen vertical to the long axis of the root and 0.4-mm-thick serial sections were made. Each section was observed with a stereomicroscope at 30× magnification to calculate the taper value of apical 1/3, middle third 1/3 and canal orifice 1/3. RESULTS: The width of MB1 root canal: maximum and minimum diameter of root apex was (0.38±0.12) mm and (0.34±0.16) mm, maximum and minimum diameter of root middle was (0.55±0.26) mm and (0.57±0.12) mm, maximum and minimum diameter of root collar was (1.13±0.34) mm and (0.59±0.18) mm. The width of MB2 root canal taper: maximum and minimum diameter of root apex was (0.25±0.13) mm and (0.28±0.10) mm, maximum and minimum diameter of root middle was (0.36±0.09) mm and (0.17±0.06) mm, maximum and minimum diameter of root collar was (0.79±0.23) mm and (0.23±0.17) mm. The taper of MB1 root canal: maximum and minimum diameter of root apical 1/3 was 0.03 and 0.01, maximum and minimum diameter of root middle 1/3 was 0.06 and 0.03, maximum and minimum diameter of root collar 1/3 was 0.10 and 0.09. The taper of MB2 root canal: maximum and minimum diameter of root apical 1/3 was 0.02 and - 0.01, maximum and minimum diameter of root middle 1/3 was 0.06 and 0.00, maximum and minimum diameter of root collar 1/3 was -0.02 and -0.02. CONCLUSIONS: MB1 has a larger width and taper, and root apical 1/3, middle 1/3, collar 1/3 have variable taper; While the width and taper of MB2 are small, and there will be upside down taper.

Livin modulates the apoptotic effects of vesicular stomatotitis virus in lung adenocarcinoma.

Vesicular stomatitis virus (VSV) has shown promise in cancer treatment. However, it achieved limited effects against lung cancer. Lung cancer has intrinsic mechanisms that render resistance to VSV. In this study, we attempted to explore the expression of the anti-apoptotic factor Livin in lung adenocarcinoma and its possible relationship to VSV vulnerability. We found VSV induced apoptosis in a time- and dose-dependent manner, with the concomitant change in the expression of Livin. We elevated the expression of Livin both transiently and stably, and the cells became insensitive to VSV treatment. We further found the BIR domain of Livin was mainly responsible for its modulation effects. This finding suggested a possible interaction with the second mitochondria-derived activator of caspase (SMAC). The knock-down of SMAC also inhibited apoptosis by VSV. The relationship was confirmed by the co-immunoprecipitation. Finally, we knocked down the endogenous Livin, and the knock-down sensitized cells to VSV treatment. Our results suggested the important role of Livin and its partner molecule in the process of VSV treatment.

Sputum matrix metalloproteinase-8 and -9 and tissue inhibitor of metalloproteinase-1 in bronchiectasis: clinical correlates and prognostic implications.

BACKGROUND AND OBJECTIVE: The triplet of airway infection, inflammation and bronchial wall destruction associated with excessive matrix metalloproteinases (MMP) release and imbalance of tissue inhibitor metalloproteinase-1 (TIMP-1) is implicated in bronchiectasis. We sought to determine the associations between sputum MMP (MMP-8, MMP-9) and TIMP-1 and the severity of bronchiectasis; the utility of MMP in predicting risks of future bronchiectasis exacerbations (BE); and the changes in MMP levels during BE. METHODS: We recruited 102 patients with stable bronchiectasis and 22 healthy subjects. For bronchiectasis patients, baseline measurements consisted of sputum inflammation and MMP measurements, bacterial culture, spirometry and chest high-resolution computed tomography (HRCT). Bronchiectasis patients were followed up for 1 year to determine the frequency of BE. Changes in MMP levels during BE were assessed in 36 bronchiectasis patients. RESULTS: Sputum MMP-8, MMP-9 and MMP-9/TIMP-1 ratio in bronchiectasis patients were significantly increased compared with healthy subjects. MMP-8 and MMP-9 levels, but not TIMP-1, were positively correlated with clinical measures, including HRCT scores, spirometry and Bronchiectasis Severity Index. Seventy-nine bronchiectasis patients were included in survival analyses of BE. Lower levels of baseline MMP-9 were associated with reduced risks of and a longer time to the first BE during follow-up. MMP-8 and MMP-9, but not TIMP-1 or MMP-9/TIMP-1 ratio, were significantly heightened during BE. CONCLUSIONS: Sputum MMP might be useful biomarkers for the assessment of bronchiectasis severity and the prediction of future risks of BE. Our results provide the rationales for the future clinical application of MMP inhibitors.

Down-regulation of Sp1 suppresses cell proliferation, clonogenicity and the expressions of stem cell markers in nasopharyngeal carcinoma.

BACKGROUND: Transcription factor Sp1 is multifaceted, with the ability to function as an oncogene or a tumor suppressor, depending on the cellular context. We previously reported that Sp1 is required for the transcriptional activation of the key oncogenes in nasopharyngeal carcinoma (NPC), including B-lymphoma mouse Moloney leukemia virus insertion region 1 (Bmi1) and centromere protein H (CENPH), but the role of Sp1 and its underlying mechanisms in NPC remained largely unexplored. The objective of this study was to investigate the cellular function of Sp1 and to verify the clinical significance of Sp1 as a potential therapeutic target in NPC. METHODS: The levels of Sp1 in the normal primary nasopharyngeal epithelial cells (NPECs) and NPC cell lines were analyzed by Quantitative Real-time RT-PCR (qRT-PCR) and Western blot. The location and expression of Sp1 in the NPC tissues were detected by immunohistochemistry staining (IHC). The effect of Sp1 knockdown on the cell proliferation, clonogenicity, anchorage-independent growth and the stem-cell like phenotype in NPC cells were evaluated by MTT, flow cytometry, clonogenicity analysis and sphere formation assay. RESULTS: The mRNA and protein levels of Sp1 were elevated in NPC cell lines than in the normal primary NPECs. Higher expression of Sp1 was found in NPC tissues with advanced clinical stage (P=0.00036). Either inhibition of Sp1 activity by mithramycin A, the FDA-approved chemotherapeutic anticancer drug or Sp1 silencing by two distinct siRNA against Sp1 suppressed the growth of NPC cells. Mechanism analysis revealed that Sp1 silencing may suppress cell proliferation, clonogenicity, anchorage-independent growth and the stem-cell like phenotype through inducing the expression of p27 and p21, and impairing the expressions of the critical stem cell transcription factors (SCTFs), including Bmi1, c-Myc and KLF4 in NPC cells. CONCLUSIONS: Sp1 was enriched in advanced NPC tissues and silencing of Sp1 significantly inhibited cell proliferation, clonogenicity, anchorage-independent growth and the stem-cell like phenotype of NPC cells, suggesting Sp1 may serve as an appealing drug target for NPC.

Low­dose radiation­induced apoptosis in human leukemia K562 cells through mitochondrial pathways.

High­dose total body irradiation (TBI) has an established role as preparative regimen for bone­marrow transplantation in the treatment of chronic myelogenous leukemia (CML), but this regimen still has a relatively high rate of acute and late toxicity. Low­dose radiation (LDR) induces apoptosis of tumor cells and has numerous beneficial effects on normal tissues, including radiation homeostasis and adaptive response. Based on the previous evidence, in the present study, K562 cells were exposed to LDR, high­dose radiation (HDR), and LDR in combination with HDR to investigate the possible mechanism of the apoptotic effect and hypersensitivity induced by LDR. The apoptotic rate increased in all radiation groups in a time­dependent manner. An upregulation of Bax protein expression and a downregulation of Bcl­xl in a dose­dependent manner in human leukemia K562 cells was observed. However, the expression of p53 protein did not change in all of the radiation cell groups. The mitochondrial membrane potential (ΔΨm) in K562 cells decreased in all of the radiation cell groups in a dose­dependent manner. Furthermore, the decrease of ΔΨm was enhanced in the LDR/HDR group compared with that in the LDR or HDR groups. The activity of caspase­3 was enhanced in all of the radiation groups. In the LDR/HDR group, the activity of caspase­3 was higher than that in the HDR or LDR groups. The present study provided preliminary experimental evidence of LDR being beneficial in combination with TBI in the treatment of CML.

Sp1 and c-Myc regulate transcription of BMI1 in nasopharyngeal carcinoma.

B-lymphoma mouse Moloney leukemia virus insertion region 1 (Bmi1), a member of the polycomb group, has elevated expression and is involved in the pathogenesis of various aggressive cancers, including nasopharyngeal carcinoma (NPC). To date, the mechanisms underlying the high expression of Bmi1 in NPC remain obscure. To gain new insights into the transcriptional regulation of BMI1, we cloned and characterized the promoter region of BMI1. Luciferase reporter assays demonstrated that the region from -783 to +375 showed significant promoter activity. With the use of a series of 5'-deletion and 3'-deletion promoter constructs in luciferase reporter assays, the +167/+232 and -536/-134 regions were found to be sufficient for full promoter activity. Transcriptional activity of the BMI1 promoter was dependent on the Sp1 binding site cluster (+181/+214) as well as the E-box elements (-181), and was abolished after mutation of the two cis-elements. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays demonstrated that Sp1 bound to the region from +181 to +214 within the BMI1 promoter. In addition, gain-of-function and loss-of-function analyses revealed that Sp1 augmented Bmi1 expression. Further investigations using immunohistochemistry and quantitative RT-PCR disclosed a significant positive correlation between the expression of Sp1 and Bmi1 in normal nasopharyngeal epithelial cells, NPC cells, and NPC tissue specimens. In addition, Myc, the known transcription factor for BMI1 in neuroblastomas, also activated the transcription of BMI1 through binding to the E-box element (-181) within its promoter, and showed a positive correlation with the mRNA level of BMI1 in NPC. In conclusion, these findings provide valuable mechanistic insights into the role of Sp1 and c-Myc in BMI1 transcription in NPC, and suggest that targeting of Sp1 or c-Myc may be a potential therapeutic strategy for NPC.

Overexpression of the truncated form of Livin reveals a complex interaction with caspase-3.

Disruption in apoptosis are involved in cancer development and progression. Livin-ß, has been identified as a critical modulator for cell death in several tumor cell lines. It was demonstrated that a truncated fragment of Livin-ß (tLivin) without its N-terminal 52 amino acids is produced in cells through protein cleavage. However, the biological consequence of the cleavage remains largely ignored. In the present study, we report that tLivin exerted a pro-apoptotic effect on cells. The subcellular localization of tLivin was mainly restricted to the cytoplasm. To explore the underlying mechanism, we observed an elevated caspase-3 activity which may account for the apoptosis. Furthermore, we observed that tLivin was further cleaved into a smaller fragment in cells. This second cleavage was possibly related to activated caspase-3. The resulted C-terminal fragment (livC) was an anti-apoptotic factor. Our study may help to deepen our understanding of the role of Livin in the regulation of cell death.

Expression of beclin 1 in bladder cancer and its clinical significance.

BACKGROUND: The aim of this study is to explore the expression of beclin 1, an autophagy gene, in bladder cancer and to evaluate its clinical and prognostic significance in patients with bladder cancer. METHODS: Beclin 1 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry in bladder cancer tissues and adjacent normal bladder tissues. The relationship between the expression of beclin 1 and clinicopathological characteristics and prognosis was statistically analyzed.
 RESULTS: mRNA level, protein expression and immunoreactivity of beclin 1 were decreased in bladder cancer tissues compared with adjacent normal tissues. Downregulation of beclin 1 was more frequent in tumors with higher histological grades (the expression of beclin 1 was reduced by 49.0% in G1 and G2, and by 71.8% in G3, p=0.010), and was also reduced by 69.5% in the muscle invasive type and by 51.1% in the non-muscle invasive type (p=0.04). Reduced beclin 1 expression was positively associated with higher histological grade and more advanced clinical stage (p<0.05). Kaplan-Meier survival analysis revealed that patients exhibiting lower beclin 1 expression experienced a shorter survival than those with higher expression (p=0.006). Cox proportional hazards regression analysis showed that beclin 1 protein is an independent predictor of survival (p=0.005).
 CONCLUSION: Beclin 1 has an influence on the progression of bladder cancer and might serve as a potential prognostic factor for patients with bladder cancer.

Upregulation of the antiapoptotic factor Livin contributes to cisplatin resistance in colon cancer cells.

The antiapoptotic factor Livin has been considered critical for tumor progression and poor prognosis for variant types of tumors. However, there are only limited reports regarding its expression and biological functions in colon cancer. Here, we examined Livin expression in four colon cancer cell lines (HCT116, RKO, KM12C, and SW620) in the presence or absence of cisplatin that was used as a model reagent. We found the different response to cisplatin was related to endogenous Livin expression level. From among a panel of apoptosis-related factors (p53, Bcl-2, Bcl-XL, BAX, and survivin), the expression of Livin was upregulated after cisplatin treatment in a dose-dependent manner. Both immunocytochemistry and nuclear cytoplasmic fractionation indicated Livin remained in the cytoplasm after treatment with cisplatin. In an attempt to explore the mechanism, we found the elevated expression of Livin was not due to the decreased degradation by proteosome but was enhanced at the mRNA level. Besides, cisplatin treatment activated the mammalian target of rapamycin (mTOR) pathway as shown by increased phosphorylation of Akt1, mTOR, S6K, and 4E-BP1, together with the elevated Livin. The PI3K inhibitor LY294002 inhibited both the phosphorylation of mTOR and upregulation of Livin. The stable overexpression of Livin inhibited the activation of caspase-3 and led to resistance to cisplatin, while the knockdown of Livin by siRNA rendered colon cancer cells more sensitive to cisplatin. Our study, along with others, highlighted the potential of Livin for cancer therapy in colon cancer.

Dosimetric verification for primary focal hypermetabolism of nasopharyngeal carcinoma patients treated with dynamic intensity-modulated radiation therapy.

OBJECTIVE: To make sure the feasibility with (18F)FDG PET/CT to guided dynamic intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma patients, by dosimetric verification before treatment. METHODS: Chose 11 patients in III~IVA nasopharyngeal carcinoma treated with functional image-guided IMRT and absolute and relative dosimetric verification by Varian 23EX LA, ionization chamber, 2DICA of I'mRT Matrixx and IBA detachable phantom. Drawing outline and making treatment plan were by different imaging techniques (CT and (18F)FDG PET/CT). The dose distributions of the various regional were realized by SMART. RESULTS: The absolute mean errors of interest area were 2.39%±0.66 using 0.6 cc ice chamber. Results using DTA method, the average relative dose measurements within our protocol (3%, 3 mm) were 87.64% at 300 MU/min in all filed. CONCLUSIONS: Dosimetric verification before IMRT is obligatory and necessary. Ionization chamber and 2DICA of I'mRT Matrixx was the effective dosimetric verification tool for primary focal hyper metabolism in functional image-guided dynamic IMRT for nasopharyngeal carcinoma. Our preliminary evidence indicates that functional image-guided dynamic IMRT is feasible.