Evaluation of MMP substrate concentration and specificity for neovascularization of hydrogel scaffolds.

Controlled vascular response in scaffolds following implantation remains a significant clinical challenge. A critical biomaterial design criterion is the synchronization of the rates of scaffold degradation and vascularized tissue formation. Matrix metalloproteinases (MMPs) are key enzymes that regulate neovascularization and extracellular matrix remodelling. Synthetic protease-sensitive hydrogels offer controllable environments for investigating the role of matrix degradation on neovascularization. In this study, PEG hydrogels containing MMP-sensitive peptides with increased catalytic activity for MMPs expressed during neovascularization were investigated. Scaffolds were functionalized with MMP-2-, MMP-14- or general collagenase-sensitive peptides and with varying peptide concentration using crosslinkers containing one (SSite) or multiple (TSite) repeats of each protease-sensitive sequence. Increasing peptide concentration enhanced the degradation kinetics of scaffolds functionalized with MMP-specific sequences while 80% of the collagenase-sensitive scaffolds remained upon exposure to MMP-2 and MMP-14. In vitro neovascularization was consistent with in vivo tissue invasion with significantly increased invasion occurring within SSite MMP-specific as compared to collagenase-sensitive hydrogels and with further invasion in TSite as compared to SSite hydrogels regardless of peptide specificity. All scaffolds supported in vivo neovascularization; however, this was not dependent on peptide specificity. These findings demonstrate that peptide concentration and specificity regulate in vivo scaffold degradation, neovascularization and matrix remodelling.

Risk factors for laryngeal cancer.

This case-control study comprised 100 histologically verified laryngeal cancer patients and 100 hospital controls matched with cases by sex, age and place of residence. The following variables were tested for their association with cancer of the larynx: marital status, educational level, hard liquor consumption, cigarette smoking, unfavorable working conditions, sudden and frequent temperature changes at work, cold housing, loud speech at work, frequent hoarseness, frequent and persistent cough, persistently swollen neck glands, tonsillectomy and laryngeal surgery. According to conditional logistic regression analysis, significant association with laryngeal cancer was found for unfavourable working conditions for more than 10 years (OR = 4.36; 95% CI = 1.92-9.91), hard liquor consumption for more than 5 years (OR = 2.59; 95% CI = 1.14-5.87), cigarette smoking for more than 10 years (OR = 7.29; 95% CI = 2.41-22.09), tonsillectomy (OR = 4.80; 95% CI = 1.61-14.30) and frequent and persistent cough prior to disease (OR = 8.17; 95% CI = 1.72-38.76).

[Epidemiologic characteristics of mortality in cancer of the tongue in Yugoslavia]. / Epidemioloske karakteristike mortaliteta raka jezika u Jugoslaviji.

The paper contains mortality data about tongue cancer in Yugoslavia for the period from 1969 to 1988. Using descriptive epidemiologic method a demographic analysis was conducted on deceased from tongue cancer according to age and sex. The chronologic analysis includes the period of 20 years, while the topographic distribution of deceased includes six Yugoslav republics. Statistic models for studying standard mortality rates were used according the method of direct standardization as well as the specific mortality rates concerned with sex and age, equation of linear trend and proportion. The results of investigation show that the average standardized mortality rate concerning tongue cancer from 1969 to 1988 in Yugoslavia amounted to 0.62 in 100,000 inhabitants. These rates are considerably higher in males (1.17%ooo) than in females (0.17%ooo). The specific rates of mortality considering age continually grow with the increase of age. They are relatively low, up to the age of 44 (males), and up to 54 (females). The examination of epidemiologic situation concerning tongue cancer in our country on the basis of total mortality trend (y = 0.62 + 0.03x) indicates a slow growth, in males (y = 0.17 + 0.07x) as well as in females (y = 0.17 + 0.01x), which points to a need for research of possible risk factors and prompt realization of adequate preventive measures.

[Mortality in laryngeal cancer in Belgrade 1982-1991]. / Smrtnost od raka larinksa u Beogradu 1982-1991. godine.

The paper reviews data on mortality caused by larynx cancer in Belgrade from 1982 to 1991. The gathered results indicate that larynx cancer was the cause of death in 2.01% on average of all deceased of all kinds of malignant tumors (3.17%, male 0.67% female), while it makes 8.18% of the deceased of malignant tumors of the respiratory tract (9.5% male, 5.21% female). The standardized mortality rates during the 10 year period occurred in 1.84 to 3.05 cases per 100,000 inhabitants (2.60%/100000 average). In males the rates were from 3.65 to 6.01%/100000 (4.91%/100000 average) and in females from 0.32 to 1.13%/100000 (0.69%/100000 average). The specific mortality rates according to age were extremely low up to the age of 44, then an abrupt increase happens, while the occurrence of the highest values is present in the oldest group. The mortality trend concerning larynx cancer during the ten year period points to the fact that there is a slight decrease as well in males (y = 5.02-0.02x) as in females (y = 1.06-0.07x).

Case-control study of risk factors in laryngeal cancer.

A case-control study with 100 cases and 100 controls was conducted to test hypothetical risk factors in laryngeal cancer. McNemar's test helped to select 25 variables, 12 of which were indicated by the conditional logistic regression analysis as independently associated with laryngeal cancer. The association was proved to be statistically significant in the case of seven risk factors; smoking more than 10 cigarettes per day (RR = 18.17; 95% CI 1.95-169.76), predominantly tinned food and meat product diet (RR = 2.65; 95% CI 1.02-6.88), long-term work exposure to low temperatures and building, fabric and metal dust (RR = 4.53; 95% CI 1.80-11.37), extended stay in closed space filled with cigarette smoke (RR = 2.67; 95% CI 1.08-6.60), recurrent hoarseness persisting for more than 1 month (RR = 12.68; 95% CI 3.28-49.03), swollen neck lymph nodes over a number of years (RR = 12.81; 95% CI 1.57-104.29). It was inferred that these seven tested variables could represent risk factors in laryngeal cancer.

Risk factors for thyroid cancer.

Case-control study comprised 100 histologically verified thyroid cancer patients (23 men, 77 women) and 100 hospital controls matched with cases by sex, age and place of residence. Various risk factors were studied to determine whether they were associated with the occurrence of thyroid cancer. According to the conditional logistic regression analysis, 6 were significantly related to the disease: Cigarette smoking (RR = 7.12 95% CI = 1.53-32.99), family history of any malignant tumors (RR = 5.84 95% CI = 1.76-19.44), history of goiter or thyroid nodules (RR = 27.69 95% CI = 3.11-246.14), long-term occupational exposure to chemicals (RR = 10.07 95% CI = 3.85-26.35), history of second primary tumors (RR = 15.49 95% CI = 3.46-69.30), and diagnostic X-rays exposure (RR = 7.56 95% CI = 2.85-20.07).

[Epidemiologic characteristics of mortality in the most common malignant tumors of the head and neck in Serbia]. / Neke epidemioloske karakteristike mortaliteta od najcescih malignih tumora glave i vrata u Srbiji.

The study has been based on official records of the Yugoslav Federal Bureau for Statistics on the mortality rate of brain, larynx, tongue and pituitary gland tumors, which represent most frequently recorded head and neck neoplasma in Yugoslavia between 1974 and 1988. In that period the standardized mortality rates were as follows: brain neoplasms 3.11%, laryngeal neoplasm 2.86%, tongue neoplasms 0.72% and pituitary gland neoplasms 0.55%. In all investigated types of neoplasms the mortality rate tended to increase, indicating that the epidemiologic course of these diseases in Serbia is unfavorable. Risk of death regarding sex shows differences among specific localizations. Males are at higher risk when brain, laryngeal and tongue neoplasms are concerned, while the mortality rate among females is higher in pituitary gland neoplasm group. According to age of patients the mortality rate is low in patients up to 44 years; as the age increases the mortality rate increases rapidly too, whatever localization of head and neck neoplasms in concerned.

[Mortality in malignant brain tumors in Yugoslavia]. / Mortalitet od malignih tumora mozga u Jugoslaviji.

Malignant tumours of head and neck, as a common group of diseases, is mentioned in Yugoslavia for the first time in 1972, where as the american authors have been studying this group of diseases as a whole since 1954 (1969). The data about death persons of malignant brain tumours (codes 191), of all causes of death (codes 000-999), of defined death causes of all the neoplasms (codes 140-209) and neoplasms of head and necks (codes 140-149, 160-161, 190-193), according to the eighth and ninth Revision of the International Classification of Diseases, Lesions and Death Causes, are based on official data of the Institute of Statistics of Yugoslavia for the period 1969-1988 (1988). In the analysis of mortality were used the standardized death rates according to the method of direct standardization after the world population by Segi (1976), further specific death rates according to sex and age, proportions and linear trend (1983). The results of these researches have shown that in the period from 1969 to 1988 there were recorded in Yugoslavia 13687 dead of malignant brain tumours in all. The average standardized mortality rate was 2.94 per 100,000 inhabitants; it is higher in men (3.59), than in women (2.40). On the basis of the results of linear trend it is shown that the average standardized rates of total mortality are increasing (y = 2.94 + 0.16x); it is in the males y = 3.59 + 0.23x, in females y = 2.40 + 0.12x. Age specific mortality rates are the highest in the group 55-64 years (10.37%). In this group the risk of dying is much greater in the males (13.63%), than in the females (7.85%).

[Epidemiologic study of laryngeal cancer in Yugoslavia]. / Epidemioloska istrazivanja raka larinksa u Jugoslaviji.

In Yugoslavia cancer of the larynx has an important position in the group of malignant tumours, especially among the malignomas of the respiratory system. According to the data on mortality, laryngeal cancer accounts for 2.67% of all tumours and 11.59% of all respiratory tract tumours during the period from 1977 to 1988. In that period the average age-adjusted mortality rate of laryngeal cancer was 3.09 per 100,000 population, much higher in mean--6.29%(000) than the women--0.53%(000). The linear trend in laryngeal cancer mortality from 1977 to 1988 points to a slight increase (y = 2.97 +/- 0.02x), in men (y = 6.03 +/- 0.04x), while in women it shows a decrease (y = 0.60--0.01x). Age specific mortality rates of laryngeal cancer are low in the age groups to 39 years in men and 49 years in women. It augments steadily from 40 and 50 years of age respectively, with the highest rates in patients above 70 years of age (39.66%(000) for men and 4.05%(000) for women).

[Mortality in malignant hemopathies in Yugoslavia]. / Smrtnost od malignih hemopatija u Jugoslaviji.

The authors have analysed the mortality of malignant haemopathies in Yugoslavia from 1978 to 1987. The standardized rate of mortality among all malignant haemopathies was from 6.5 to 7.2%000. These rates were higher in males (7.8-8.8%000), than in the females (4.8-5.9%000). The mortality of this group of malignant tumors shows a decreasing tendency, which is more evident in females than in males. Since Hodgkin's disease and lymphoid leukemia participate with about 50% in the structure of mortality from all malignant hemopathies, and for that reason, mortality from these two diseases is especially analysed. The standardized rate of mortality from Hodgkin's disease was between 1.7-2.5%000 (males 2.1-3.2%000; females 1.3-2.0%000). Mortality from this malignant haemopathy has a tendency of decreasing, which is approximately of the same intensity in both sexes. Mortality from lymphoid leukemia in the period between 1978 and 1987 was from 0.7 to 1.2%000 (males 0.9-1.7%000; females 0.5-1.0%000). The mortality trend from lymphoid leukemia shows a similar slight decrease in males and females.

[Mortality in carcinoma of the thyroid gland in Yugoslavia]. / Smrtnost od karcinoma tiroidne zlezde u Jugoslaviji.

The article dealing with thyroid gland cancer in Yugoslavia is based on data on the mortality rate over the period from 1971 to 1985. During the observed period the average proportion of thyroid gland cancer was 0.51% (males-0.30%; females-0.81%) in the whole group of malignant tumours in Yugoslavia. In the same period the standardized mortality rate was 0.52 per 100,000 persons, with the following risk difference between sexes: males-0.40; females-0.63 per 100,000 persons. The mortality trend of thyroid gland cancer in Yugoslavia showed a slight increase from 1971 to 1985 (9y = 0.480 + 0.006x).