Effect of three-year consumption of erythritol,xylitol and sorbitol candies on various plaque and salivary caries-related variables

Objective

The objective of the present paper is to report results from oral biologic studies carried out in connection with a caries study.

Methods

Samples of whole-mouth saliva and dental plaque were collected from initially 7- to 8-year-old subjects who participated in a 3-year school-based programme investigating the effect of the consumption of polyol-containing candies on caries rates. The subjects were randomized in three cohorts, consumed erythritol, xylitol, or sorbitol candies. The daily polyol consumption from the candies was approximately 7.5 g.

Results

A significant reduction in dental plaque weight from baseline (p < 0.05) occurred in the erythritol group during almost all intervention years while no changes were found in xylitol and sorbitol groups. Usage of polyol candies had no significant or consistent effect on the levels of plaque protein, glucose, glycerol, or calcium, determined yearly in connection with caries examinations. After three years, the plaque of erythritol-receiving subjects contained significantly (p < 0.05) lower levels of acetic acid and propionic acid than that of subjects receiving xylitol or sorbitol. Lactic acid levels partly followed the same pattern. The consumption of erythritol was generally associated with significantly (p < 0.05) lower counts of salivary and plaque mutans streptococci compared with the other groups. There was no change in salivary Lactobacillus levels.

Conclusion

Three-year consumption of erythritol-containing candies by initially 7- to 8-year old children was associated with reduced plaque growth, lower levels of plaque acetic acid and propionic acid, and reduced oral counts of mutans streptococci compared with the consumption of xylitol or sorbitol candies.     

A phase-II study of combination of pegylated interferon alfa-2a and capecitabine in locally advanced or metastatic renal cell cancer

Purpose

Combination of capecitabine and interferon has shown activity in metastatic renal cell carcinoma. Pegylated interferons might have more clinical activity and fewer side effects. This study evaluated the efficacy, tolerability, and safety of the combination of capecitabine and pegylated interferon alfa-2a.

Methods

In this open label, single institution, non-randomized phase-II first-line study, 26 patients were included. Capecitabine was administered 2,000 mg/m² daily for 14 days followed by 1 week rest. Pegylated interferon alfa-2a was given once as weekly injections with a fixed dose of 180 μg. Overall survival, progression-free survival, and response rates were evaluated; safety and tolerability were monitored.

Results

Response rate was 27, with 4% complete responses. Stable disease was achieved in 42%. The treatment discontinued in 4 (15%) patients before first response evaluation because of toxicity. The median progression-free survival was 7.5 months; the median overall survival was 17 months. Grades 3–4 toxicity was seen in 46% of patients, but in 93% of cycles no serious toxicity was experienced. Dose reductions had to be done, but in 81% of cycles intensity of 70% or more was possible. Quality of life was better in cycle five than in the base line.

Conclusions

The combination had moderate, but manageable toxicity. In the future studies, lower dose for capecitabine is recommended. The combination was active and the response rates seen here were in line with phase-II studies on former combinations of non-pegylated interferons. One complete remission was achieved.     

Radiation-induced morphological changes and radiocurability in squamous cell carcinoma of the head and neck region. A preliminary report.

Tissue samples taken from 22 patients before and during radical irradiation of squamous cell carcinomas in the head and neck region were studied by light and electron microscopy. The changes in keratinization pattern at the ultrastructural level seemed to be correlated with the outcome of the radiotherapy. The irradiation induced several cellular changes, of which nuclear atypia was the most prominent. This atypia was considered to be mainly due to cell death rather than to an aggressive nature of the tumor, because the number of mitoses decreased at the same time. The tumor invasion pattern remained unchanged. The keratinization pattern remained almost unchanged at the light microscopical level, but a slight increase of intracellular filaments and desmosomes was found in the electron microscopic study. The amount of intercellular filaments increased in three patients out of four with complete remission (CR), but in no case with tumor dissemination (n = 3) during radiotherapy. In patients with local persistent tumor or a local recurrence (LP + LR) (n = 15) the filaments either increased, decreased or remained unchanged. The number of desmosomes either increased or remained unchanged in three of four CR patients, in 13 of 15 LP + LR patients and in only one of three patients with tumor dissemination. They decreased in two patients with tumor dissemination, but only in one case with CR and in 2 cases with LP + LR. It is suggested that changes in cytoskeleton and desmosomes might be important in anchorage of tumor cells locally and might have value for prediction of the tumor response to radiotherapy. Further studies on larger materials are, however, needed before more definite conclusions can be drawn.     

Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy.

BACKGROUND: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. PATIENTS AND METHODS: Five hundred and twenty-five women below the age of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. RESULTS: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). CONCLUSION: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS.     

Soluble immunological parameters and early prognosis of renal cell cancer patients

In local or metastatic cancer, a prognostic tumour marker could be a valuable tool in the selection of different treatments. In renal cell cancer (RCC) no such markers have been available. We therefore evaluated the association between several pretreatment serum markers, tumour classification and short term survival in RCC patients. Serum samples were collected before surgery and three months thereafter from 24 RCC patients. Interleukin-6 (IL-6), IL- 12, soluble IL-2 receptor (sIL-2R) and intercellular adhesion molecule-1 (sICAM-1) were measured in serum samples using specific commercial enzyme immunoassay kits. Serum IL-6, sIL-2R and sICAM-1 levels before nephrectomy were significantly higher in non-local tumours than in local ones (mean IL-6 53 pg/ml versus 6.3 pg/ml, and sICAM-1 443 ng/ml versus 290 ng/ml, sIL-2R 3779 pg/ml versus 1796 pg/ml). In contrast, IL-12 levels were higher in local tumours (148 versus 102 pg/ml) and the levels increased significantly (P < 0.005) after removal of the primary tumour in patients with local disease. All patients with local tumours had normal IL-6 values, while only one with a non-local tumour had IL-6 levels below 10 pg/ml. In addition, IL-6 and sICAM-1 levels before operation were significantly higher in patients with short (less than one year) survival (p=0.007 to IL-6 and p=0.006 to sICAM-1). In contrast, patients with shorter survival had significantly lower IL-12 (p=0.03) levels. Our findings suggest that RCC induces changes in several immunological parameters. These soluble immunological factors, IL-6, IL-12, sIL-2R and sICAM-1, might have a role as prognostic factors in RCC.     

Serum angiogenin levels predict treatment response in patients with stage IV melanoma

This work was conducted to find out new potential serum markers and study their role as predictive factors in patients with metastatic melanoma. Serum samples from 68 patients with stage IV malignant melanoma were collected just before current treatment and screened for 79 different cytokines by using a multi-cytokine array. Angiogenin, which is a protein capable of promoting angiogenesis, was found to be markedly elevated among a sub-group of patients with progressive disease (PD) and thus was subjected to further analysis. The mean serum angiogenin level was 270 ng/ml and the median 236 ng/ml (STD 163 ng/ml). Concentrations were significantly higher among men than in women (P = 0.031), whereas patient's age, site of the primary tumour, Clark's or Breslow's classifications were not associated with angiogenin levels. Patients with only lymph node metastases had markedly lower angiogenin levels than those with metastases at other sites (P = 0.05). High angiogenin levels were significantly (P = 0.015; Kruskal-Wallis) associated with poor treatment response with chemoimmunotherapy. Treatment-related survival (TRS) was shorter (10 months) in patients with above-median values than in those with below-median levels (19 months, P = NS). Cox multivariate regression model was used to control for the confounding by the classical prognostic factors of melanoma (age, sex, disease burden, performance score, site of metastases). Disease burden was the only variable that remained in the model as a significant independent predictor of TRS (P = 0.044). These data suggest that serum angiogenin levels might be of predictive value in the evaluation of treatment response for patients with stage IV melanoma.     

Increased risk of certain second primary malignancies in patients treated for well-differentiated thyroid cancer

Background

The objective was to evaluate the incidence of second primary malignancies (SPMs) in thyroid cancer patients compared to age- and gender-matched controls without thyroid cancer from the general population of the same region.

Methods

Tampere and Oulu University Hospitals treated 910 patients with well-differentiated thyroid cancer during 1981–2002. The Finnish cancer registry provided follow-up data for patients and controls (n = 4542) for an average of 16 years. The incidence of invasive malignancies per 10 000 person-years was calculated and compared between patients and controls. The follow-up period ended December 31st, 2011.

Results

Young patients <40 years [Rate Ratio (RR) 1.73, p = 0.037] and patients diagnosed since 1996 (RR 1.51, p = 0.029) had an increased incidence of SPMs. Patients had an increased risk of sarcomas and soft tissue tumours (RR 4.37, p = 0.004) and haematological and lymphatic malignancies (RR 1.87, p = 0.035), especially non-Hodgkin lymphomas (RR 2.78, p = 0.035). The overall incidence of SPMs was not statistically higher in patients (109 SPMs/910 patients vs. 500 SPMs/4542 controls, RR 1.12, p = 0.269). Most patients were radioiodine-treated (81 %). The risk of SPMs with low cumulative radioiodine doses was RR 0.94 (≤3.7 GBq, p = 0.650) and with high doses RR 1.37 (>3.7 GBq, p = 0.143). Cumulative radioiodine dose increased during the study period.

Conclusions

The overall incidence of SPMs was not higher in patients than in controls. The incidence of SPMs in thyroid carcinoma patients was higher in patients <40 years old and patients diagnosed since 1996. The incidence of sarcomas and lymphomas was higher in patients than in controls.

     

Leukemia-inhibitory factor stimulates breast,kidney and prostate cancer cell proliferation by paracrine and autocrine pathways

Leukemia-inhibitory factor (LIF) is an inflammatory cytokine with pleiotropic activities. LIF was originally described as a differentiation factor of a murine leukemia cell line and was subsequently found to possess a broad spectrum of biological functions. Although LIF has been extensively studied in the hematopoietic system, little is known about its effects in solid tumors. We investigated the role of LIF in breast, kidney and prostate cancers. Using a clonogenic assay, we found that LIF significantly stimulated proliferation of 2 estrogen receptor-positive breast cancer cell lines (MCF-7 and T47-D) in a dose-dependent fashion at concentrations ranging from 10 to 200 ng/ml. This effect was observed both in the presence of FCS and under serum- and estrogen-free culture conditions, suggesting that the effect of LIF is direct and does not depend on estrogen or any other cytokine. Neither line produced LIF protein, as assessed by ELISA. In contrast, the estrogen receptor-negative breast cancer line MDA MB-231 produced LIF but did not respond to either LIF or its neutralizing antibodies. Similarly, increasing concentrations of LIF did not affect the growth of primary kidney (A-498), metastatic kidney (ACHN) and prostate (DU 145) cancer cell lines. These lines produce LIF, however, and antibodies to LIF significantly suppressed their proliferation, suggesting that they were maximally stimulated by the endogenously produced cytokine. Taken together, our data suggest that LIF acts as either a paracrine or an autocrine growth factor for breast, kidney and prostate cancers. © 1996 Wiley-Liss, Inc.