Clinical Diagnosis of Cervical Lesions Combined with Programmed Death Ligand and miR-124 Detection in Peripheral Blood.

Objective: This study aims to analyze the expression of colposcopy combined with PD-L1 (programmed death ligand-1) and miR-124 (microRNA-124) in CC (cervical cancer) and CIN (cervical precancerous lesions), providing insights for clinical screening and diagnosis of these conditions. Method: A total of 60 patients with suspicious cervical lesions were selected from the gynecological clinic at Jinhua People's Hospital between June 2021 and December 2021. The patients were divided into three groups: LSIL (low-grade squamous intraepithelial lesions), HSIL (high-grade squamous intraepithelial lesions), and no SIL group, with 20 cases per group. This sample distribution ensures a comprehensive representation of different lesion severities. Pathological tissues were collected from each group for immunohistochemistry analysis to assess PD-L1 expression. Peripheral blood samples were also obtained from the patients for PCR analysis to evaluate miR-124 expression. These techniques allowed us to examine the expression levels of PD-L1 and miR-124 in the samples accurately. Result: The HSIL group exhibited a higher rate of positive PD-L1 expression compared to the LSIL and no lesion groups. Additionally, the expression level of miR-124 was lower in the HSIL group compared to the LSIL and no lesion groups (P < .05). Statistical measures such as means, standard deviations, and P values were used to quantify these differences, providing a more comprehensive understanding of the results. Conclusions: Combining colposcopy results with the expression of PD-L1 and miR-124 can effectively evaluate precancerous lesions of cervical cancer. This combined approach holds significant clinical implications by potentially enhancing early detection, diagnosis, and treatment strategies for CC and CIN. Further research in this area may lead to improved patient outcomes and contribute to the development of targeted therapies.

Analysis of Curcumin as a Radiosensitizer in Cancer Therapy with Serum Survivin Examination: Randomised Control Trial.

OBJECTIVE: One of the important treatments for cervical cancer is radiation therapy. This study sought to determine the role of curcumin as a radio-sensitizing agent for use with radiation therapy for cervical cancer. To accomplish this, we assessed the levels of survivin, which is an anti-apoptotic protein that plays a role in cell division and apoptosis inhibition. METHOD: This study used a quasi-experimental design, including a pretest-posttest control group design approach. The study subjects included cervical carcinoma stage IIB-IIIB patients who were scheduled to undergo surgery at the Hasan Sadikin Hospital Bandung during the research period. The advanced cervical cancer patients were assigned to two groups: i) those who received curcumin + radiation therapy and ii) those who received placebo + radiation therapy. RESULTS: In the group treated with curcumin + radiation, 15 (75%) patients showed decreased survivin levels and 5 (25%) showed increased survivin levels. Whereas, in the placebo + radiation group, there were 8 (40%) patients who showed decreased survivin levels and 12 (60%) who showed increased survivin levels. CONCLUSION: In conclusion, curcumin is an effective, alternative radiosensitizer agent for application in cervical cancer treatment.
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Oxidative damage and antioxidants in cervical cancer.

The pathogenesis of cervical cancer is related to oxidative damage caused by persistent infection by one of the oncogenic types of human papillomavirus (HPV). This damage comes from oxidative stress, which is the imbalance caused by the increase in reactive oxygen and nitrogen species and impaired antioxidant mechanisms, promoting tumor progression through metabolic processes. The incorporation of HPV into the cellular genome leads to the expression of oncoproteins, which are associated with chronic inflammation and increased production of reactive oxygen species, oxidizing proteins, lipids and DNA. The increase in these parameters is related, in general, to the reduction of circulating levels of enzymatic antioxidants-superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase; and non-enzymatic antioxidants-reduced glutathione, coenzyme Q10 and vitamins A, C and E, according to tumor staging. In contrast, some enzymatic antioxidants suffer upregulation in the tumor tissue as a way of adapting to the oxidative environment generated by themselves, such as glutathione-S-transferase, reduced glutathione, glutathione peroxidase, superoxide dismutase 2, induced nitric oxide synthase, peroxiredoxins 1, 3 and 6, and thioredoxin reductase 2. The decrease in the expression and activity of certain circulatory antioxidants and increasing the redox status of the tumor cells are thus key to cervical carcinoma prognosis. In addition, vitamin deficit is considered a possible modifiable risk factor by supplementation, since the cellular functions can have a protective effect on the development of cervical cancer. In this review, we will discuss the impact of oxidative damage on cervical cancer progression, as well as the main oxidative markers and therapeutic potentialities of antioxidants.

Diagnostic potential of ionomic profile in the plasma of cervical cancer patients receiving neoadjuvant chemoradiotherapy.

BACKGROUND AND AIM: Major and trace elements play an important role in human body, and it has been reported that ionomic distribution differ greatly in tumor patients. The aim of the present study was to investigate the effects of cisplatin-based neoadjuvant chemoradiotherapy on the ionomic profile in human plasma as a potential biomarker for the therapeutic effects of cervical cancer. METHOD: Thirty-seven patients with cervical cancer receiving neoadjuvant chemoradiotherapy were included in this study, pretherapy and post-treatment blood samples were collected and concentrations of 24 ions were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: The results showed that after cisplatin chemotherapy and radiotherapy, patients' plasma Pt level significantly increased, Na, Mg, P, K, Ca, Se, Cu, Zn, Se, Sr, Ba levels significantly decreased (P < 0.01), and Al, Cu ions were significantly correlated with the treatment effect (P < 0.05). In addition, the pattern of elemental correlations changed dramatically after the neoadjuvant chemoradiotherapy. CONCLUSION: The results indicated that the plasma ionomic profile may serve as a quick and convenient tool to reflect the therapeutic effect of cisplatin-based chemoradiotherapy in cervical cancer patients, and supplement of certain essential elements may be of great importance for the maintenance of ion homeostasis in human body and for the reduction of adverse effect of chemotherapy and radiotherapy.

The Relationship between the Serum Level of Selenium and Cervical Intraepithelial Neoplasia: A Comparative Study in a Population of Nigerian Women

Objective: To determine the relationship between the serum level of selenium and cervical intraepithelial neoplasia (CIN). Methods: A case controlled study that compared the serum level of selenium in 45 women with CIN (cases) to 45 women (age matched controls) with normal cervical cytology. Socio-demographic data and information on known risk factors for cervical cancer among the sample was compared between both groups using inferential statistics. Results: There was no significant difference in the mean selenium values between the cases and controls [p- 0.076, 95% CI (-15.08 ­ 0.76)]. However, subgroup analysis showed a statistically significant difference between patients with normal cervical cytology, CIN I, II and III (p= 0.021). In addition, there was also significant difference in the selenium level between women with normal cervical cytology and CIN III (p value = 0.016) with a significant inverse linear trend (p= 0.025). Conclusion: With increasing severity of CIN, a significant reduction in the level of selenium in serum was observed. This reducing value of serum selenium, a surrogate marker for increased oxidative stress, may be important factor for the development of persistent HPV infection and in particular high grade CIN III lesions. This observation requires further research.

Serum Se, Ni, and As are associated with HPV infection and CIN2+ among Uyghur women in rural China.

BACKGROUND: Cervical cancer incidence and mortality is high in Uyghur ethnics. Their life style and dietary habit were different from other ethnics living together. Study on the role of trace elements in HPV infection and cervical lesion of Uyghur minority is needed for future intervention and prevention work. METHODS: In total, 833 Uyghur women were randomly selected from the screening site and hospital. The concentrations of the trace elements As, Fe, Cd, Ni, Cu, Zn, Mn, and Se were determined by atomic absorption spectrophotometry and inductively coupled plasma atomic emission spectroscopy. Univariate analysis was performed with chi-squared test between the HPV-positive and HPV-negative groups and between the case group and the control group. Multivariate analysis was performed with logistic regression. RESULTS: An As concentration ≥ 0.02 mg/kg was a risk factor for HPV infection (OR > 1, P < 0.05), and Ni concentration ≥ 0.1232 mg/kg and Se concentration ≥ 0.02 mg/kg were protective factors (OR < 1, P < 0.05). Concentrations of Fe ≥ 6.9153 mmol/L and As ≥0.02 mg/kg were risk factors for CIN2+ (OR > 1, P < 0.05), and concentrations of Ni ≥0.0965 mg/kg and Se ≥0.02 mg/kg were protective factors (OR < 1, P < 0.05). CONCLUSIONS: Low serum concentrations of Se and Ni and a high serum concentration of As might be related to HPV infection and CIN2+ in Uyghur women in rural China.

Comparative analysis of serum trace element levels in women with invasive cervical cancer in Lagos, Nigeria.

INTRODUCTION: Trace elements although present in minute quantities in human blood, they play a vital role in many biochemical enzymatic reactions and have been examined critically as a potential key factor in various human diseases including cancers. This study was aimed to determine the association between serum levels of trace elements and invasive cancer of the cervix. METHODS: This was an analytical cross-sectional study carried out among women seen at the Lagos University Teaching Hospital (LUTH). Fifty histologically diagnosed patients with squamous cells carcinoma of the cervix, who had not had any treatment and 100 cancer-free volunteers were recruited. A structured interviewer-administered questionnaire was used to collect relevant data following which venous blood sample was obtained from each participant. Serum zinc, copper and selenium concentrations were then measured. The associations of serum trace elements and invasive cervical cancer were tested using the independent sample t-test. All significances were reported at P<0.05. RESULTS: There were significantly low serum levels of zinc and selenium in cervical cancer patients with no significant difference seen in the serum level of copper among cervical cancer patients compared to their cancer-free control counterparts. CONCLUSION: These alterations in trace elements levels may be important in the pathogenesis of cervical cancers; however, future robust prospective studies are needed to determine if routine provision of these supplements will result in improved cervical cancer treatment outcomes in Nigerian women.

Enhanced efficacy with reduced toxicity of chemotherapy drug 5-fluorouracil by synergistic treatment with Abnormal Savda Munziq from Uyghur medicine.

BACKGROUND: Abnormal Savda Munziq (ASMq) is a traditional prescription in Uyghur Medicine, and its treatment of complex diseases such as tumors and asthma has been proven to be effective in Uyghur medical clinical practice. The efficacy-enhancing and toxicity-reducing properties of ASMq were studied on mice with transplanted cervical cancer (U27) tumors, which were treated with 5-fluorouracil (5-FU) in this work. METHODS: To investigate the synergistic effect of ASMq and 5-FU on U27 cells, inhibitory effects on cell proliferation were determined through a MTT assay. 48 Kunming mice which were randomly divided in to 6 groups: control group, model group, 5-FU group, 5-FU combine with ASMq low-dose group, 5-FU combine with ASMq medium-dose group, and 5-FU combine with ASMq high- dose group, the inhibition rate of the tumor, the viscera indexes, and the content of serum tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. The expression levels of transforming growth factor-ß1 (TGF-ß1) and human papillomavirus type 16 E2 (HPV16 E2) protein were assessed by Western blot. Pathological changes in the liver were observed. RESULT: The inhibition rates of tumors, the 5-FU + ASMq.H group(80.64%), 5-FU + ASMq.M group (90.67%), 5-FU + ASMq.L group (72.03%) and 5-FU group (66.89%), clearly indicated that the effects of tumor inhibition. The thymus index and spleen index were increased, and the serum concentration of TNF-α increased while ALT and AST concentrations were decreased, and TNF-α protein expression were increased while TGF-ß1 and HPV16 E2 were decreased. ASMq might can improve livers central vein hyperemia and interstitial edema, and preserve the radial structure of the hepatic cords. CONCLUSIONS: The results suggested that ASMq might reduce toxicity and enhance the efficacy of the chemotherapeutic drug 5-fluorouracil in the treatment of cervical carcinoma.

Serum Selenium Levels and Cervical Cancer: Systematic Review and Meta-Analysis.

Several studies have investigated the relationship between serum Se concentration and cervical cancer, but the results were inconsistent. Thus, we conducted a systematic review and meta-analysis to evaluate the association between serum selenium levels and cervical cancer. Twelve studies investigating the association by univariate analysis and five studies by multivariate analysis were identified after a systematic search of PubMed, Wanfang, CNKI, and SinoMed databases. Standard mean differences (SMD) or odds ratios (OR) with the corresponding 95% confidence intervals (CI) were pooled to compare the selenium levels between different groups. In univariate analysis, serum selenium levels in cervical cancer cases were significantly lower than in controls (SMD = -4.86, 95% CI -6.03-3.69). Subgroup analysis showed consistent results. In multivariate analysis, serum selenium levels in cervical cancer cases were also significantly lower than in controls (OR = 0.55, 95% CI 0.42-0.73). After treatment, the serum selenium levels increased significantly (SMD = 2.59, 95% CI 0.50-4.69). In conclusion, high serum selenium levels were associated with cervical cancer, and selenium exposure might be a protective factor for cervical cancer.

Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia: a Randomized, Double-Blind, Placebo-Controlled Trial.

We are not aware of any study examining the effects of long term vitamin D administration on regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). This study was performed to evaluate the effects of long-term vitamin D administration on regression and metabolic status of patients with CIN1. This randomized, double-blind, placebo-controlled trial was performed among 58 women diagnosed with CIN1. CIN1 diagnosis was performed based on specific diagnostic procedures of biopsy, pathological diagnosis, and colposcopy. Patients were randomly allocated into two groups to take 50,000 IU vitamin D3 supplements (n = 29) or placebo (n = 29) every 2 weeks for 6 months. Fasting blood samples were taken at the beginning of the study and end-of-trial to measure related markers. After 6 months of vitamin D administration, greater percentage of women in the vitamin D group had regressed CIN1 (84.6 vs. 53.8%, P = 0.01) than those in the placebo group. Long-term vitamin D supplementation increased serum-25(OH) vitamin D levels in the intervention group compared to the placebo group (+12.3 ± 11.4 vs. -0.1 ± 3.7 ng/mL, P < 0.001). In addition, vitamin D intake led to significant decreases in serum insulin levels (-5.3 ± 7.3 vs. +2.4 ± 5.9 µIU/mL, P < 0.001), homeostasis model of assessment-insulin resistance (-1.2 ± 1.6 vs. +0.5 ± 1.2, P < 0.001), homeostatic model assessment-Beta cell function (P = 0.005) and a significant elevation in quantitative insulin sensitivity check index (+0.03 ± 0.04 vs. -0.007 ± 0.02, P < 0.001) compared with the placebo group. Additionally, significant increases in plasma nitric oxide (NO) (+15.5 ± 10.3 vs. +4.0 ± 13.4 µmol/L, P = 0.001), total antioxidant capacity (TAC) (P = 0.04), total glutathione (GSH) (+11.8 ± 153.5 vs. -294.2 ± 595.1 µmol/L, P = 0.01) and a significant reduction in plasma malondialdehyde (MDA) levels (-0.8 ± 1.0 vs. -0.03 ± 1.4 µmol/L, P = 0.03) were observed following the administration of vitamin D supplements compared with the placebo group. In conclusion, vitamin D3 administration for 6 months among women with CIN1 resulted in its regression and had beneficial effects on markers of insulin metabolism, plasma NO, TAC, GSH and MDA levels. Clinical trial registration number www.irct.ir : IRCT201412065623N30.

Association between serum folate level and cervical cancer: a meta-analysis.

PURPOSE: The aim of this study was to evaluate the association between serum folate level and cervical cancer. METHODS: PubMed, Medline, Springer, Elsevier Science Direct, Cochrane Library and Google scholar were searched for relevant trials. Rev.Man5.1 and Stata 11.0 software were applied for this meta-analysis. Odds Ratio (OR) and 95 % confidence intervals (95 % CI) were collected and calculated in a fixed-effects model or a random-effects model when appropriate. Subgroup analysis was performed by sample size, participant's geographical location and definition of deficient serum folate level. RESULTS: A total of 6 case-control studies including 2383 participants were included in the meta-analysis. The overall meta-analysis showed that there were significant differences between cases and controls, suggesting that deficient serum folate level was associated with the increased risk of cervical cancer. After stratification subgroup analysis, significant difference was also found in subgroup with sample size <500 as well as in Asian population, but not in subgroup with sample size ≥500, American populations as well as different definition of deficient serum folate level (<6.4 ng/ml or others). CONCLUSIONS: Based on our meta-analysis, deficiency of serum folate level was associated with the increased risk of cervical cancer among Asian populations.

Comparison of serum and tissue levels of trace elements in different models of cervical cancer.

Cervical cancer is a leading cause of death by cancer among women worldwide. It is necessary to develop and refine cervical cancer models to more accurately reflect human tumor type. The relevance of cervical cancer to trace element was studied in this paper. By means of quantitative trace element analysis in models and patients with cervical cancer, the tissue and serum levels of trace elements in papillomaviruses-induced cancer models were more similar to that of patients than the levels in models induced by HeLa cell and methylcholanthrene. The results reflect papillomaviruses model most accurately mimic in vivo carcinogenesis of patients with cervical cancer. It will have a superior predictive value over HeLa cell and methylcholanthrene models in pre-clinical trials. The papillomaviruses-induced cervical cancer can provide more reliable models for testing the efficacy of drugs in treating human cancers.

Effect of Paris saponin on antitumor and immune function in U14 tumor-bearing mice.

We evaluated the effect of Paris saponin on inhibition of cervical cancer in mice and on immune regulation in tumor-bearing mice. MTT assay was used to examine the effect of Paris saponin on U14 cell proliferatiosn in vitro; the ascites tumor model of U14 cervical cancer was established to observe the effect of Paris saponin on inhibition of the tumor and on survival time of mice; and serum IL-4 and IFN-γ levels in tumor-bearing mice were detected. The Paris saponin showed significant inhibitory effect on growth of cervical cancer U14 cells both in vitro and in vivo, prolonged the survival time of mice, increased the serum IFN-γ level of tumor-bearing mice, and reduced the serum IL-4 level. The Paris saponin can inhibit U14 cell growth and prolong survival time of mice; it is speculated that the Paris saponin may express its anti-tumor activity by improving the body's immune system.

Serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment.

AIM: In the present study, the effect of chemo and radio therapies on serum trace elements content and antioxidant activity in blood serum of cervical cancer patients was evaluated. METHODS: Among 104 cervical cancer patients selected for the present study, 54 and 50 patients were treated with chemo- and radiotherapy respectively. Plasma Se, Zn, Cu and some enzymatic antioxidants activities were estimated in serum before and after the treatment. RESULTS: The decreased levels of serum trace elements, glutathione peroxidase activity and total antioxidant capacity, and increased malondialdehyde, glutathion reductase was observed in cervical cancer patients when compared to healthy controls. The increased concentration of serum Se, Zn was observed in patients treated with chemotherapy. Simultaneously there was a significant (P < 0.001) increase in glutathione peroxidase and total antioxidant capacity, and significant decrease (P < 0.05) in malondialdehyde and glutathion reductase levels in the serum of patients treated with chemotherapy compared to the patients treated with radiotherapy. CONCLUSION: The results demonstrated that chemotherapy but not radiotherapy results in significant increase in the trace elements levels and antioxidant activities in blood serum of cervical cancer patients.

Impact of treatment planning target volumen (PTV) size on radiation induced diarrhoea following selenium supplementation in gynecologic radiation oncology--a subgroup analysis of a multicenter, phase III trial.

BACKGROUND: In a previous analysis (Int J Radiat Oncol Biol Phys 70:828-835,2010), we assessed whether an adjuvant supplementation with selenium (Se) improves Se status and reduces the radiation-induced side-effects of patients treated by adjuvant radiotherapy (RT) for cervical and uterine cancer. Now, a potential relation between the planning target volume (PTV) of the RT and the Se effect concerning radiation induced diarrhoea was evaluated in detail. METHODS: Whole blood Se concentrations had been measured in patients with cervical (n=11) and uterine cancer (n=70) after surgical treatment, during, and at the end of RT. Patients with initial Se concentrations of less than 84 µg/l were categorized as Se-deficient and randomized before RT to receive Se (as sodium selenite) per os on the days of RT, or to receive no supplement during RT. Diarrhoea was graded according to the Common Toxicity Criteria system (CTC, Version 2a). The evaluation of the PTV of the RT was ascertained with the help of a specialised computer-assisted treatment planning software used for radiation planning procedure. RESULTS: A total of 81 patients had been randomized for the initial supplementation study, 39 of which received Se [selenium group, SeG] and 42 serving as controls [control group, CG]. Mean Se levels did not differ between SeG and CG upon study initiation, but were significantly higher in the SeG compared to the CG at the end of RT. The actuarial incidence of at least CTC 2 radiation induced diarrhoea in the SeG was 20.5% compared to 44.5% in the CG (p=0.04). The median PTV in both groups was 1302 ml (916-4608). With a PTV of <= 1302 ml (n=41) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 22.3% (4 of 18 patients) compared to 34.8% (8 of 23 patients) in the CG (p=0.50). In patients with a PTV of > 1302 ml (n=40) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 19.1% (4 of 21 patients) versus 52.6% (10 of 19 patients) in the CG (p=0.046). CONCLUSIONS: Se supplementation during RT was effective to improve blood Se status in Se-deficient cervical and uterine cancer patients, and reduces episodes and severity of RT-induced diarrhoea. This effect was most pronounced and significant in patients with large PTV (> 1302 ml).

Detection and genotyping of high-risk HPV and evaluation of anti-oxidant status in cervical carcinoma patients in Tamil Nadu State, India--a case control study.

Cervical cancer is the second common type of cancer among women worldwide, with the human papillomavirus (HPV) recognized as the major causative agent. The HPV 16/18 prevalance in cervical cancer patients from the Trichy and Coimbatore districts of Tamil Nadu state, India, was evaluated in addition to an assessment of oxidative stress and antioxidant status. MDA, GSH, GPx, GST, SOD, vitamin C and vitamin E were estimated in the plasma and erythrocytes of the twenty patients and an equal number of age matched normal subjects as controls. 119 paraffin embedded tissue samples were collected to perform DNA extraction and genotyping of HPV 16/18 using specific primers. Plasma and erythrocyte TBARS level was significantly elevated in the cervical cancer patients compared to normal. It was observed that SOD, GPx, GSH levels in the erythrocyte and plasma was significantly lower in cervical cancer patients, as well as GST and Vitamins E and C levels in the plasma and catalase enzyme levels in the erythrocytes. Genotyping showed 57% positive for HPV16 and 18% for HPV18, indicating that vaccination against these two will effectively reduce the burden associated with the disease. These findings suggest possible use of antioxidant supplementation as prophylactic agents for prevention and treatment of cervical cancer.

Chemopreventive potential and safety profile of a Curcuma longa extract in women with cervical low-grade squamous intraepithelial neoplasia.

OBJECTIVE: To determine whether Curcuma longa Linn extract, NBFR-03, can arrest low-grade squamous intraepithelial neoplasia (LSIL) a 12 week intervention study was performed. METHODS: Of a total of 1473 women undergoing Pap smear screening, 88 cases had LSIL. Only those with persistent LSIL subsequent to antimicrobial therapy, and willing to follow the protocol (N=21), were included for clinical examination, Pap smears, colposcopy, clinical biochemistry, urinalysis and assessment of serum IL-6, being conducted before and after treatment. Standardised NBFR-03 (0.2gm) capsules were administered, twice daily, for 12 weeks. RESULTS: None progressed to higher grade lesion as assessed by Pap smears and colposcopy. Sixteen cases regressed to atypia, ASCUS or inflammatory pattern; 3 persisted as LSIL, 1 discontinued early because of itching, and 1 did not start. None developed any significant abnormality clinically or biochemically. Micrometry showed a significant reduction in nuclear diameter and nucleocytoplasmic ratio after treatment (p<0.02, and <0.05 respectively). Serum IL-6 levels showed a significant decline (mean 248∓ 156 (SEM) vs 27.7∓ 10.5 (SEM) pg/ ml; p<0.05). CONCLUSION: Use of NBFR-03 for 12 weeks was associated with an arrest or regression of LSIL in Pap smears and colposcopy, with reduction in the circulating IL-6 levels.

Antitumor activity of polysaccharides isolated from Patrinia heterophylla.

The research investigated the effect of Patrinia heterophylla Bunge (Valerianaceae) polysaccharides (PHB-P1) on U14-bearing mice. The tumor weight of mice treated with PHB-P1 (30, 60 mg/kg body weight) was significantly lower than that of the control group, a decrease of serum lactate dehydrogenase (LDH) activity was observed, and the serum alkaline phosphatase (AKP) level was increased slightly. The number of apoptotic tumor cells was significantly increased in the mice by treatment of PHB-P1 (30, 60 mg/kgbw). Cell cycle analysis showed the accumulation of tumor cells in the G2/M phase and a relative decrease of the S phase. By the immunohistochemical analysis, PHB-P1 (30, 60 mg/kgbw) might up-regulate the expression of p53 and Bax, and significantly inhibited the expression of Bcl-2 in tumor tissues. In conclusion, PHB-P1 could inhibit tumor growth and induce tumor cell apoptosis.

Multicenter, phase 3 trial comparing selenium supplementation with observation in gynecologic radiation oncology.

PURPOSE: We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy (RT) for cervical and uterine cancer. METHODS AND MATERIALS: Whole-blood selenium concentrations were measured in patients with cervical cancer (n = 11) and uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT, and 6 weeks after RT. Patients with initial selenium concentrations of less than 84µg/L were randomized before RT either to receive 500 µg of selenium (in the form of sodium selenite [selenase, biosyn Arzneimittel GmbH, Fellbach, Germany]) by mouth on the days of RT and 300 µg of selenium on the days without RT or to receive no supplement during RT. The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects. RESULTS: A total of 81 patients were randomized. We enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT. The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2) in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood parameters, Eastern Cooperative Oncology Group performance status, and self-reported quality of life were not different between the groups. CONCLUSIONS: Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea.