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Biomedical subjects

D Santini

Publications and source records attributed to D Santini.

At least 181 records · Page 10Linked to original sources

Expression of p21 in non small cell lung cancer relationship with PCNA.

The first cyclin dependent kinase inhibitor to be discovered was the p21 cdk interacting protein (a.k.a., WAF1, Cip1, CAP20, Sdi1, mda6). p21 expression may or may not be dependent on p53. This pathway also inhibits DNA replication by merit of p21's interaction with PCNA, but it has also been shown that this same inhibitory interaction with p21 does not affect PCNA DNA repair abilities. We assessed the immunohistochemical expression of p21 protein in 60 curative surgical resected non small cell lung cancers relating it to the expression of PCNA to clarify the contribution of the p21/PCNA pathway to the development of NSCLC. We did not find any relationship between PCNA and p21 expression. This last result may indicate that the mechanism by which PCNA controls the DNA repair is the most important activity of this protein during lung cancer progression and development, compared to its contribution to cell proliferation. In fact, this last event is strongly counteracted by p21 expression, which in this last case works as an inhibitor of PCNA expression. In conclusion this study highlighted the important role of the p21/PCNA pathway in lung carcinogenesis, pointing out the contribution of PCNA to the response to lung aggression and not only it's role as a proliferation index. Therefore, these results offer a background to further study to evaluate potential novel therapeutic approaches to lung cancer treatment.

Adenocarcinoma↗

Atypical case of metastatic undifferentiated prostate carcinoma in a 36 years old man: clinical report and literature review.

Prostate carcinoma occurs infrequently in patient less than 50 years old with an incidence of 0.8% to 1.1%. In literature are described less than 20 cases occurred in younger men (< 40 years old). A 36 year-old man with a two-months history of lower back pain, anorexia and loss of weight, showed at clinical examination a mild enlargement of inguinal lymph nodes and right inferior leg and scrotus edema. CT scan demonstrated marked enlargement and fusion of pelvic, inguinal, sacral and periaortic nodes with a pelvic mass that caused local ureterohydronephrosis and obstruction of the urinary flow. X-rays showed osteoblastic metastases. At total body scintigram were observed fixation areas corresponding to lumbar metamers, pelvis, thigh bones, left humeral head, left acromioclavicular articulation and multiple ribs. Tumor markers resulted negative except prostate specific antigen (PSA: 500 mgr/ml) and prostatic acid phosphatase (PAP: 208 U/l); prostate biopsy showed an undifferentiated carcinoma. The patient was submitted to right percutaneous nephrostomy, chemotherapy (PEB, cisplatinum, etoposide and bleomycin for 6 cycles) and ormonotherapy (LHRH analogues) reporting a clinical partial response. After 6 months the disease progressed and was started a second line chemotherapy. After 18 months from diagnosis patient is still alive with progressing disease. Our patient represents, with respect to many features, an original clinical case of prostate carcinoma occurring in young age, for the atypical association of an undifferentiated carcinoma with high levels of PSA and PAP and with osteoblastic-pattern of bone metastases. Further studies would be useful to identify new risk factors for development of prostate cancer in young men in order to achieve early diagnosis.

Acid Phosphatase↗

Intrapulmonary teratoma associated with thymic tissue.

A case of benign, cystic intrapulmonary teratoma occurring in the right lobe of a 22-year old female is described with grossly and microscopically findings. The connection between the tumor and the segmental bronchus, together with the absence of germ cell neoplasms in other locations, clearly established the true intrapulmonary nature of the lesion. The unusual finding of thymic tissue within the wall supports the possible origin from the third pharyngeal pouch.

Actins↗

Detection of circulating malignant cells by RT-PCR in long-term clinically disease-free I stage melanoma patients.

Recently, reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of circulating tumor cells has been suggested as a potential technique for staging cancer. In this report, 43 melanoma patients (including 4 in situ melanoma patients) were tested for tyrosinase mRNA in blood by RT-PCR. All patients had melanoma thinner than 1.5 mm (stage I). Circulating melanoma cells were detected in 8 (18.6%) out of 43 MM patients tested: 5 (16.1%) of 31 patients with melanoma thinner than 0.76 mm and 3 (42.8%) out of 7 patients with melanoma thicker than 0.76 mm. Moreover, in the tyrosinase-negative group we found only 4/31 patients (13%) with histologic signs of regression, but in the tyrosinase-positive group, 3 out of 8 patients (37.5%) showed, at histologic examination, signs of regression. At the time of this analysis all the patients enrolled (tyrosinase-negative and tyrosinase-positive ones) were free of disease, probably due to the short median time of follow-up after the inclusion in the study. The presence of regression is an important cause of melanoma understaging and the tyrosinase test could represent an effective tool in order to achieve a realistic staging in this subgroup of melanoma patients. Probably, maximum sensitivity of the diagnostic RT-PCR approach to monitor MM patients with either localized or advanced disease could be achieved by using additional markers expressed with high frequencies in melanoma. We propose that one such marker could be the sign of regression.

Adolescent↗

Oxaliplatin may induce cytokine-release syndrome in colorectal cancer patients.

INTRODUCTION: Oxaliplatin, a third-generation platinum analogue, is a novel compound with proven anti-tumor activity in colorectal cancer. Moreover, oxaliplatin appears to be relatively well tolerated and easy to handle, even on an outpatient basis. PATIENTS AND METHODS: Five advanced colorectal cancer patients treated with oxaliplatin-based chemotherapy developed, after the end of oxaliplatin infusion, similar idiosyncratic reactions characterized by chills, high fever, hypotension, abdominal pain, nausea and often diarrhoea. Venous blood for IL-6 and TNF-alpha assessment was drawn just after the beginning of the reaction and 15 and 30 minutes later. After drawing the third venous sample, intravenous dexamethasone (8 mg) was administered and the drawing of other two venous samples was performed (180 and 360 minutes after the beginning of the reaction). RESULTS: TNF-alpha and IL-6 serum concentrations significantly decreased after steroid therapy administration. The decrease of TNF-alpha and IL-6 levels went along with the clinical complete regression of symptoms and signs in all the 5 patients. No statistically significant correlation was found between other laboratory parameters and basal cytokine levels or cytokine decrease after steroid therapy. DISCUSSION: Our results clearly show that that idiosyncratic reaction observed in colorectal cancer patients after oxaliplatin infusion may be due to a massive release of cytokines such as TNF-alpha and IL-6. Symptom regression following steroid therapy administration went along with significant decrease of cytokines levels, confirming that TNF-alpha and IL-6 play a role in the pathogenesis of this reaction.

Abdominal Pain↗

The antineoplastic treatment in the elderly.

More than 550,000 American people died for cancer only in 1998 and more than third of them were over 65 years of age. According to recent data in next decade more than 70% of all the deaths for tumour will be verified in the population over 65 years. The cancers mostly frequently associated with the deaths in the elderly population are the tumour of the lung, colon, prostate and breast. Therefore the geriatrics oncology is progressively assuming a central and essential role within the medical oncology. One of the aspects of great interest in the treatment of the cancers of the elderly patient (> 65 years) is the study about some pharmacokinetic modifications of the antitumour medicines in such band of age, and the study about some pattern of toxicity characteristics in the elderly patients. In this ambit there are a few studies in literature devoted specifically to such aspect. This study represents an attempt of revision of the literature finalized to analyse the toxicological and pharmacokinetic characteristics of the principal chemotherapeutic agents used in the therapy of elderly patients affected with cancer. In the last part of the review we have tried to synthesize the state of the art of the achieved results about the medicines that have shown a better therapeutic index and a better impact on the clinical benefit in such population of patients.

Age Factors↗

Matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor (TIMP-2) are prognostic factors in cervical cancer, related to invasive disease but not to high-risk human papillomavirus (HPV) or virus persistence after treatment of CIN.

OBJECTIVE: Matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor (TIMP-2) are important regulators of cancer invasion and metastasis. Their associations to high-risk (HR) human papillomavirus (HPV) in cervical intra-epithelial neoplasia (CIN) and cervical cancer (CC) are unexplored and their prognostic significance in CC remains controversial. MATERIALS AND METHODS: As part of our HPV-PathogenISS study, a series of 150 CCs and 152 CIN lesions were examined using immunohistochemical (IHC) staining for MMP-2 and TIMP-2 and tested for HPV using PCR with 3 primer sets (MY09/11, GP5+/GP6+, SPF). Follow-up data were available from all squamous cell carcinoma patients and 67 CIN lesions had been monitored with serial PCR for HPV after cone treatment. RESULTS: MMP-2 increased with the grade of CIN, with major up-regulation upon transition to invasive cancer (OR 20.78) (95%CI 7.16-60.23) (p=0.0001). TIMP-2 retained its normal expression until CIN3, with dramatic down-regulation in invasive disease (p=0.0001 for trend). Thus, the MMP2:TIMP-2 ratio increased with progressive CIN, exceeding the value 1.0 only in invasive disease. Both MMP-2 and TIMP-2 are highly specific (TIMP-2; 100%) discriminators of CIN with 100% positive predictive value (TIMP-2), but suffer from low sensitivity and negative predictive value. Neither MMP-2 nor TIMP-2 showed any significant association with HR HPV or virus persistence/clearance. TIMP-2 (but not MMP-2) was a significant predictor of survival in univariate (Kaplan-Meier) analysis (p=0.007), but lost its significance in multivariate (Cox) analysis. CONCLUSION: The activities of MMP-2 and TIMP-2 in cervical carcinogenesis seem to be unrelated to HR-HPV The inverse MMP-2:TIMP-2 ratio is a sign of poor prognosis. A combination of a TIMP-2 assay with another test showing high SE and high NPV (e.g., HCII for HPV) should provide a potential screening tool capable of accurate detection of CIN.

Adult↗

Paraneoplastic syndromes: what we know and what we should know.

Paraneoplastic syndromes are a group of clinical disorders associated with malignant diseases that are not directly related to the physical effects of primary or metastatic tumor. Those that are associated with the secretion of circulating peptides may be used as a useful tool in monitoring patients after the start of chemotherapy. Most of the paraneoplastic syndromes represent an interesting tool of internal medicine. Moreover, they also represent a starting point for a work up in patients with an occult neoplasia, even though the clinical presentation may be very multifaceted. As consequence of all these considerations, the present editorial represents a useful tool for a rational approach to paraneoplastic syndromes.

Humans↗

[Clinical evaluation of the efficacy of the combined determination of serum markers CEA, CA 19.9, CA 72.4 as indexes of gastro-intestinal tract neoplasms].

The aim of our study was to evaluate the usefulness of the tumor markers CA 72.4, CEA and CA 19.9 in the monitoring of gastrointestinal carcinomas. Our experience demonstrated the usefulness of the determination of CA 72.4 in the follow up of patients with gastrointestinal neoplasms.

Antigens, Tumor-Associated, Carbohydrate↗

Epidermal growth factor receptor (EGF-R) and transforming growth factor alpha (TGFA) expression in different endometrial cancers.

The role of epidermal growth factor receptor (EGF-R) and transforming growth factor alpha (TGFA) in endometrial cancer is still controversial. In this study the immunostaining of EGF-R and TGFA, investigated in 44 cases, proved to be related to endometrial cancer histotype regardless of the tumor grade or the extent of myometrial invasion. In fact, EGF-R expression was observed in 12.5% (1/8) of cases with classical endometrioid adenocarcinoma, in 91% (10/11) with endometrial adenocarcinoma and benign squamous metaplasia, and in 35% (6/17) with adenosquamous carcinoma. TGFA expression was concomitant with EGF-R in the first two histotypes, and was present in about 50% (9/17) of the latter. Conversely, in mucinous and serous papillary adenocarcinoma, EGF-R and TGFA immunostaining was not observed. In conclusion, EGF-R positivity was observed in endometrial cancer with squamous differentiation, especially in those cases with benign squamous metaplasia. EGF-R and TGFA coexpression appeared as a constant feature of benign squamous metaplasia.

Endometrial Neoplasms↗