Significance of the Ki-67 proliferation index in the assessment of the therapeutic response to cisplatin-based chemotherapy in patients with advanced cervical cancer.

OBJECTIVE: The purposes of this study were to examine the therapeutic response of advanced cervical cancer to Ki-67 proliferative index (Ki-67 PI) dependent cisplatin chemotherapy, and to determine Ki-67 PI referential value that is expected to provide a satisfactory therapeutic response of cervical cancer to cisplatin chemotherapy. PATIENTS AND METHODS: This prospective study enrolled 59 patients treated for cervical cancer at Clinic for Oncology, Clinical Center Nis, Serbia. According to the obtained Ki-67 PI values, patients were divided into three groups, and all the patients received the same cytostatic, cisplatin. Therapeutic response to chemotherapy was evaluated in relation to disease progression presence or absence and progression-free survival after a year follow-up since the first chemotherapy. RESULTS: Survival rate increases with an increase of Ki-67 PI by Kaplan-Meier survival analysis, meaning that survival rate is statistically significantly shorter in the group of patients with Ki-67 PI < 40% in comparison to patients from other two groups (p=0.010). Mann-Whitney test confirmed a statistically significant increase in survival rate among the groups of patients formed according to Ki-67 PI (p<0.05). Kaplan-Meier survival analysis confirmed that the mean survival rate in the group of patients with Ki-67 PI values over 60% is statistically significantly longer in comparison to patients with Ki-67 PI values below or equal 60% (p<0.001). CONCLUSIONS: Advanced cervical cancer with a high Ki-67 PI expression responds better to cisplatin-based chemotherapy, thus resulting in a longer survival rate. The values of Ki-67 PI were determined: high Ki-67 PI (≥ 60%), moderate Ki-67 PI (40-60%), and low Ki-67 PI (≤ 40%).

Monosodium glutamate induces apoptosis in naive and memory human B cells.

The aim of this study was to establish the existence of mGluR7 in normal B lymphocytes and analyse the effect of monosodium glutamate (MSG) on B cell apoptosis in vitro. B cells were purified by magnetic cell sorting using anti-CD19-coupled magnetic beads. Cells (10(6)/ml) were cultured with increasing MSG concentrations (1-100 mM). Detection of apoptosis by flow cytometry was performed using the Annexin V-FITC/Propidium iodide (PI) apoptosis detection kit. Naïve and memory B cell population were identified by CD27 staining. Expression of GluRs was determined using PCR. Exposure to increasing MSG concentrations displayed dose dependent effect on B cell viability altogether, ranging from 35% with 100 mM up to 80% with 1 mM MSG. Moreover, the number of late apoptotic cells as well as necrotic cells was dose dependant. Both CD27- as well as CD27+ B cells were affected by MSG. Basal expression of GluRs7 was detected in unstimulated B cells. Glutamate induced apoptosis can be seen in memory as well as naive B cell population and is probably mediated through mGluR7, whose expression in B cells we also confirmed. Our study suggests a new possible mechanism of crosstalk between the nervous and the immune system through glutamate as a potential key mediator (Fig. 4, Ref. 27). Full Text (Free, PDF) www.bmj.sk.

Ascorbic acid modulates monosodium glutamate induced cytotoxicity in rat thymus.

BACKGROUND: Monosodium glutamate (MSG) is a commonly used flavor enhancer in modern nutrition. It has been shown that administration of MSG induces toxic effects in various regions of brain, thymus, liver and kidney. Also, it is well-documented that Vitamin C (ascorbic acid) has a protective role in MSG-induced cytotoxicity in rat liver, kidney and various brain regions, but has not been studied in thymus. OBJECTIVES: In the present study, we examined the possible protective role of Vitamin C in MSG-induced cytotoxicity in adult (Kindly indicate the strain of rat) rat thymus. MATERIAL AND METHODS: MSG was administrated intraperitoneally (4 mg/g of body weight), with or without Vitamin C (500 mg/kg of body weight), for six consecutive days. Animals were sacrificed at 1st, 7th and 14th day of last MSG dose. RESULTS: This study demonstrates that MSG administration in animals significantly decreases cell viability with significant down-regulation of Bcl-2 protein, while Bax protein expression was not significantly changed in rat thymocytes. Vitamin C was effective in ameliorating the effect of MSG in rat thymocytes by increasing the proportion of viable cells and up-regulating the expression of Bcl-2 protein in rat thymocytes. CONCLUSION: These results suggest that the treatment with Vitamin C may prevent the MSG-induced cytotoxicity in rat thymocytes by up-regulating Bcl-2 protein expression resulting in a change in Bcl-2/Bax protein ratio (Tab. 1, Fig. 1, Ref. 32). Full Text (Free, PDF) www.bmj.sk.