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Biomedical subjects

G Stanta

Publications and source records attributed to G Stanta.

At least 37 records · Page 2Linked to original sources

Reduced expression of CDKN2a/P16INK4a in mycosis fungoides.

Alterations in the CDKN2a gene have been demonstrated in a wide range of human tumors including hematopoietic malignancies. To verify whether altered CDKN2a expression is involved in the pathogenesis of mycosis fungoides (MF), we examined mRNA expression in 20 patients with MF by RT-PCR and dot blot hybridization. CDKN2a mRNA expression was undetectable in 5 of the 20 patients (25%), intermediate in 13 (65%) and high in 2 (10%). Immunohistochemical studies, which were performed in ten patients, revealed that in the four patients showing no mRNA, p16INK4a was expressed in <1% of neoplastic lymphocytes whereas in the four patients with an intermediate mRNA level, specific nuclear staining was present in 1-25% of tumor cells. In the two patients with high levels of CDKN2a mRNA, >25% of neoplastic lymphocytes stained positively. No direct correlation between clinicopathological and molecular findings was evident in our patients. DNA mutational analysis revealed no alterations in a total of six patients examined. Our results indicate that the lack of CDKN2a expression, as found in 25% of the patients, may have a pathogenetic role in MF even though the absence of CDKN2a mRNA was not associated with point mutations or minor gene deletions.

Adolescent↗

Causes of death and clinical diagnostic errors in extreme aged hospitalized people: a retrospective clinical-necropsy survey.

BACKGROUND: There are little data on causes of death in extreme aged. We compared, using autopsy findings, main cause of death, overall disease status, and accuracy rate of clinical diagnoses in extreme aged and persons dying at younger ages. METHODS: We reviewed the complete clinical and autopsy records of 114 consecutive inpatients (97 women, 17 men, age range 97-106, mean 99, median 98) who died in Trieste, Italy, and represented 99% of all extreme-aged person deaths in the hospital and 70% in the area. The control group included 151 patients (66 women, 85 men, age range 65-74, mean 70, median 70) who died during the same period in that hospital. RESULTS: Vascular and respiratory diseases together caused 84% of deaths in extreme aged. The main causes of death were pneumonia (n = 40, 35%), pulmonary embolism (n = 16, 14%), stroke (n = 12, 11%), and myocardial infarction (n = 8, 7%). Cancer was responsible for 6% (7/114) of deaths in extreme aged and 42% (64/151) in the control group. In 5% of extreme aged, autopsy findings did not explain death. The premortem diagnostic accuracy rate for clinical diagnoses was good in 44% of extreme aged, sufficient in 18%, poor in 28%, and not evaluable in 10%, and was significantly different from controls. Pneumonia, pulmonary embolism, and myocardial infarction were markedly underestimated by clinicians in both groups. CONCLUSIONS: Extreme aged die mainly of cardiovascular and respiratory diseases and, in most cases, of acute events. Senescence is a rare cause of death. Death from cancer is substantially lower than in persons dying at younger ages. In contrast to no autopsy studies, most extreme aged in our study were found to have specific diseases that explained their deaths.

Aged↗

Molecular characterization of intraductal breast carcinomas.

In situ duct carcinoma (DCIS) is a heterogeneous group of lesions which has recently been subdivided into three types: well-differentiated (type I), intermediately differentiated (type II) and poorly differentiated (type III) DCIS. Fourteen cases of DCIS and 11 of DCIS with minimal invasion were analysed for mRNA levels of beta-actin, EGFR, c-cerbB2, MTS1, k-ras, RB, BRCA1, cyclin E, and c-myc genes. A microdissection technique was used on paraffin-embedded tissue. A statistically significantly higher expression of cyclin E oncogene and MTS1 tumor suppressor gene was seen in type III DCIS than in the other types, while no significant differences in the mRNA expression patterns of the other genes were observed. These data are consistent with the fact that poorly differentiated DCIS is a readily recognizable class of tumours that have a particularly aggressive behaviour and probably unique histogenesis.

Biomarkers, Tumor↗

RNA quantitative analysis from fixed and paraffin-embedded tissues: membrane hybridization and capillary electrophoresis.

Fixed and paraffin-embedded tissues from pathology department archives are available for RNA expression analysis. We describe a general method for quantitation of specific RNA sequence extracted from single 6-8-micron human histological tissue sections cut from paraffin blocks. For each specific mRNA, the range of linear relationship between the log of the initial total RNA concentration and the log of the specific product after reverse transcription (RT)-PCR must be established. We usually perform RT with avian myeloblastosis virus (AMV)-RT, using specific antisense primers and a variable number of cycles of PCR amplification. The number of cycles must be adjusted within the range in which a linear relationship exists between the log of the amount of amplification product and the number of cycles. The quantity of specific product is standardized relative to beta-actin mRNA to normalize for the degree of RNA degradation, which can be quite different among samples. The amplification products were quantified by dot blot and 32P-labeled hybridization probe or by capillary electrophoresis with a laser-induced fluorescence detector. The intratest variation range was for the dot blot mean +/- 10% standard deviation (SD) and for the capillary electrophoresis mean +/- 3% SD.

Actins↗

[Thyroid metastasis due to right colonic carcinoma].

Clinical evident metastases to the thyroid gland are rarely found antemortem. A case of a 62 year-old man with a history of right colonic carcinoma, who presented a mass in the right lobe of his thyroid gland one year after the removal of a metachronous metastasis in his right lung, is presented. The tumour of the thyroid was found to be metastatic adenocarcinoma from his previous colonic cancer. The clinical finding of metastases to the thyroid gland is rare, particularly from a colorectal primary neoplasm. However, the possibility of a tumour of the thyroid gland representing a secondary malignancy is to be considered in any patient with a prior history of cancer.

English Abstract↗

Cancer risk in first-degree relatives of children with malignant tumours (Province of Trieste, Italy).

We conducted a population-based cohort study in the province of Trieste, Italy, to assess whether the first-degree relatives of children with malignancies had an increased risk of cancer compared with the general population. We examined cancers occurring in all first-degree relatives of children who experienced malignancies under the age of 15 years between 1971 and 1993 (probands). A cohort of the 394 relatives of the 125 probands contributed 7,939 person-years of observation. Among the relatives as a whole, we found a statistically significant increased risk of developing all malignancies except non-melanoma skin carcinoma (21 observed relatives with cancer and 12.46 expected, for a standardized incidence ratio [SIR] of 1.69), of developing breast cancer (SIR = 3.09) and of developing haemolymphatic system neoplasms (SIR = 4.03). This was mainly due to the excess cancer risk in the relatives of probands with intracranial tumours, who showed a significant 3.1-fold risk for developing all cancers but non-melanoma skin tumours. Our findings and the previously reported steep rise in the incidence of childhood brain tumours in our area may imply that not only genetic factors but also shared environmental agents might be involved in the observed aggregation of cancer in the families of probands with intracranial tumours.

Adolescent↗

Detection of Borrelia burgdorferi DNA and complement membrane attack complex deposits in the sural nerve of a patient with chronic polyneuropathy and tertiary Lyme disease.

We report a patient who developed a chronic sensory-motor polyneuropathy and a progressive myelopathy 4 years after a tick bite. An increased serum antibody titer to Borrelia burgdorferi suggested a diagnosis of Lyme neuroborreliosis, although a concomitant cervical spondylosis probably contributed to spinal cord damage. Treatment with ceftriaxone resulted in a marked improvement of neuropathic symptoms, providing indirect evidence of spirochetal infection. Search for B. burgdorferi DNA by polymerase chain reaction amplification on sural nerve confirmed the diagnosis, demonstrating that the spirochete localized in the peripheral nervous system. The presence of complement membrane attack complex deposits and macrophage infiltrates around epineurial vessels and within the endoneurium suggests that the neuropathy in our patient was immune-mediated.

Aged↗

Cigarette smoking and histologic type of lung cancer in men.

STUDY OBJECTIVES: To determine whether intensity, duration, age at initiation, and cessation of cigarette smoking act differently in the development of various histologic types of lung cancer. DESIGN: A case-control study among deceased men who underwent autopsy, a procedure that involves approximately 73% of all local deaths. SETTING: The Province of Trieste in northeastern Italy PARTICIPANTS: Seven hundred fifty-five patients with lung cancer, including 267 with squamous cell carcinoma, 218 with small cell carcinoma, 90 with large cell carcinoma, 158 with adenocarcinoma, and 22 with other histologic types, and 755 control subjects who had died of causes other than chronic lung diseases and certain tumors. Information on smoking habits, residential history, and occupational exposure was obtained from each subject's next of kin. RESULTS: Compared with nonsmokers, the odds ratio (OR) for current smokers was 13.4 for all types combined, 18.8 for squamous cell carcinoma, 14.3 for small cell carcinoma, 34.3 for large cell carcinoma, and 7.9 for adenocarcinoma. Intensity of smoking, duration, age at starting, and dose were all directly associated with all histologic types of lung cancer, although the OR was lower for adenocarcinoma than for other cell types. When results were restricted to ever smokers, exposure-response curves were similar across histologic types. The risk of lung cancer attributable to smoking was 88% for all types combined, 91% for squamous cell carcinoma, 89% for small cell carcinoma, 95% for large cell carcinoma, and 82% for adenocarcinoma. CONCLUSIONS: This study confirms that cigarette smoking causes all types of lung cancer, but the proportion of cases attributable to smoking is lower for adenocarcinoma than for other types, due to a higher proportion of nonsmokers.

Adenocarcinoma↗

EGFr and c-erB2mRNA expression in urinary bladder superficial carcinomas.

AIM: The biological behaviour of superficial type transitional carcinomas of the urinary bladder can not be predicted. To try to differentiate those tumors that will present aggressive behaviour with infiltrative recurrences from those that will not, we studied, at the mRNA level, the expression of two membrane proteins, EGFr and c-erbB2, and of k-ras oncogene. METHODS: The mRNAs relative quantitation as performed, after RT-PCR, from histological sections cut from formalin-fixed and paraffin-embedded tissues. Twenty-three patients with urinary bladder transitional carcinoma have been studied for EGF-receptor, c-erbB2 and k-ras oncogene. The expression has been correlated with the outcomes of the follow-up period (infiltrative or superficial recurrences). RESULTS: The mRNA or EGFr was in average more expressed in tumors that continue to be superficial in the relapses, but for c-erbB2 the level of mRNA was similar in both, the more and less aggressive groups. The expression of k-ras was higher in cases associated with more infiltrative tumor relapses. CONCLUSIONS: In this preliminary study we did not identify any specific marker that can clearly predict the prognosis of superficial type transitional carcinoma of the urinary bladder; only k-ras expression is connected in some cases with the aggressiveness of the tumors. The expression of EGFr gave us intriguing results, it is in fact higher in the superficial carcinomas that do not tend to become infiltrative of the urinary bladder wall.

Journal Article↗

Cancer of the oldest old. What we have learned from autopsy studies.

Cancer in the oldest old is a novel problem, due to the recent burgeoning of the population aged 85 and older. This article addresses three critical questions related to cancer in the oldest old: Does the incidence of cancer increase after age 95? Is cancer a common cause of death for the oldest old? Is cancer accurately diagnosed in the oldest old? The authors analyzed a group of 507 autopsies of elderly, divided in three age groups, 75 90 years, 95 99, and over 99 (centenarians). The prevalence of cancer was 35% among the younger persons and 20% and 16% respectively for those aged 95 99 and for the centenarians. A fourth of the patients in the younger group died from cancer but only 9.5% of the people between 95 and 98 years and 7.1% of the centenarians died from cancer. The cancer was the direct cause of death for 67% of the younger persons and 41% of patients belonging to the two oldest groups. The prevalence of metastases was 63% for tumors occurring in persons aged 75 90, 32% in persons aged 95 98, and 29% in the centenarians. Cancer had been accurately diagnosed prior to death in 67.4% of persons aged 75 90, in 38.5% of those aged 95 99, and 29.4% of the centenarian. Cancer as cause of death had been underestimated in 16% of the cases in the younger persons and in almost 50% of cases of the oldest old. This study suggests that the incidence of cancer and the importance of cancer as a cause of death may decline after age 95 and that the clinical diagnoses underestimate significantly both the incidence of cancer and the prevalence of cancer deaths in the oldest old.

Age Distribution↗

Air pollution and lung cancer in Trieste, Italy: spatial analysis of risk as a function of distance from sources.

To investigate the relationship between four sources of environmental pollution (shipyard, iron foundry, incinerator, and city center) and lung cancer risk, we conducted a case-control study of decreased men in Trieste, Italy. We identified 755 cases of lung cancer and 755 controls through the local autopsy registry. Information on smoking habits, occupational history, and place of residence were obtained from the subject's next of kin. The case-control design was used to properly account for subject-specific confounders, which represent a major problem in geographical analysis. Spatial models were used to evaluate the effect of sources of pollution on lung cancer after adjustment for age, smoking habits, likelihood of exposure to occupational carcinogens, and levels of air particulate. The models are based on distance from the sources and enable estimation of the risk gradient and directional effects separately for each source. The risk of lung cancer was highly related to the city center (p = 0.0243), with an excess relative risk at zero distance of 2.2 and a smooth decrease moving away from the source (-0.015), and related to the incinerator (p = 0.0098), with an excess relative risk of 6.7 in the source and a very steep decrease (-0.176). These results are consistent with findings of previous analyses and provide further evidence that air pollution is a moderate risk factor of lung cancer.

Air Pollutants↗