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Biomedical subjects

G Viale

Publications and source records attributed to G Viale.

At least 19 recordsLinked to original sources

Navigating uncertainties and evidence gaps in adjuvant therapy for premenopausal women with HR+/HER2- breast cancer.

Premenopausal women with hormone receptor-positive (HR+)/HER2-negative early breast cancer represent a clinically distinct population, characterized by more aggressive tumor biology, unique survivorship concerns, and complex treatment decision-making. Although evidence from dedicated trials and subgroup analyses is available, management remains challenging because data are heterogeneous, evolving, and often extrapolated from broader populations that include predominantly postmenopausal women. Adjuvant endocrine therapy, with the addition of CDK4/6 inhibitors in selected higher-risk patients, remains the cornerstone of treatment; however major uncertainties persist regarding the optimal use of ovarian function suppression, the interpretation of genomic assays to inform chemotherapy decisions, the selection of candidates for extended endocrine therapy, and the management of adherence, treatment-related toxicities, pregnancy-related issues, and survivorship concerns. Here, we synthesize current evidence across these domains and propose a pragmatic clinical framework to support individualized treatment strategies and optimize care for this population in the contemporary therapeutic landscape.

HR+/HER2- early breast cancer

Progesterone receptor immunoreactivity in pancreatic endocrine tumors. An immunocytochemical study of 156 neuroendocrine tumors of the pancreas, gastrointestinal and respiratory tracts, and skin.

BACKGROUND: The immunoreactivity for progesterone receptors (PR) of the majority of endocrine cells of the human pancreas has prompted the authors to investigate if PR expression is maintained in pancreatic endocrine tumors and is correlated with the main clinicopathologic features of these neoplasms. Furthermore, the study has been extended to other neuroendocrine cells and tumors to determine whether PR immunoreactivity is a common feature of neuroendocrine cells and tumors other than those of the pancreas. METHODS: One hundred fifty six neuroendocrine tumors of the pancreas, gastrointestinal and respiratory tracts, and skin were immunostained for PR with three different monoclonal antibodies and for estrogen receptors (ER). Additional immunostainings for general neuroendocrine markers and for pancreatic hormones were performed in selected cases. RESULTS: Nuclear immunoreactivity for PR has been documented in the neoplastic cells of 56 (58.33%) of 96 pancreatic endocrine tumors. PR immunoreactivity was not influenced by the sex and age of the patients or the occurrence of a clinical syndrome related to inappropriate hormone secretion. Tumors synthesizing pancreatic polypeptide, glucagon, and insulin expressed PR in higher percentages (80%, 75%, and 66%, respectively) than those producing other pancreatic hormones or those that were not functioning. Irrespective of the functionally different tumor types, PR immunoreactivity showed a significant correlation (P = 0.0003) with the absence of metastases and the lack of tumor invasion of neighboring organs or of large vessels. As opposed to normal and neoplastic islet cells, the neuroendocrine cells and tumors of the gastrointestinal tract, respiratory tract, and skin did not show any PR immunoreactivity, with the single exception of a typical carcinoid tumor of the lung. ER were not identified in any pancreatic or extrapancreatic neuroendocrine cells or tumors. CONCLUSIONS: Nuclear PR are immunocytochemically detectable in most pancreatic endocrine tumors and are correlated significantly to the absence of pathologic evidence for malignancy. Conversely, PR expression has not been found in normal and neoplastic endocrine cells and tumors investigated.

Adenoma, Islet Cell

Malignant rhabdoid tumour of the uterus: an immunohistochemical and ultrastructural study.

Malignant rhabdoid tumours (MRTs) are highly aggressive neoplasms which most frequently occur in the kidney of young children. Several cases of primary MRT occurring in extra-renal sites have been reported, particularly in the soft tissues. We report a case of primary MRT of the uterus, a very rare site for this neoplasm, with morphological, immunohistochemical and ultrastructural features corresponding to restrictive morphological criteria for MRT. The possible differential diagnoses were considered.

Adult

Abnormal p53 immunoreactivity and prognosis in node-negative breast carcinomas with long-term follow-up.

The expression of the p53 gene product was investigated immunocytochemically in a retrospective series of 164 formalin-fixed paraffin-embedded invasive breast carcinomas with pathologically proven negative lymph nodes. Overall, 78 tumors (48%) showed a variable degree of p53 immunoreactivity. Among these, 38 cases were low expressors (1-10% p53 immunoreactive tumor cells), 21 moderate expressors (10-50% immunoreactive cells) and 19 high expressors (> 50% immunoreactive cells). Abnormal p53 expression correlated significantly with tumor size, histological and nuclear grade, DNA ploidy, mitotic rate and proliferation index, and with the lack of estrogen receptors. Disease-free and adjusted survival analysis of the 124 node-negative patients with long term (more than 10 years) follow-up, however, did not reveal an independent prognostic role for p53 expression. These data suggest that the evaluation of p53 immunoreactivity may only play a role in a multiparametric prognostic assessment of node-negative breast carcinoma.

Biomarkers, Tumor

Gastric giardiasis.

AIMS: To assess the prevalence of gastric giardiasis in patients undergoing upper gastrointestinal endoscopy, and to define the clinicopathological correlates of gastric Giardia lamblia infection. METHODS: Consecutive gastric biopsy specimens (n = 15,023) from 11,085 patients, taken at Feltre City Hospital (north eastern Italy) from January 1986 to December 1991, were histologically and immunocytochemically examined for the occurrence of G lamblia trophozoites. Three gastric biopsy specimens from patients harbouring G lamblia infection, who repeated endoscopy before treatment, were also examined electron microscopically. RESULTS: Forty one patients (0.37% of the population study) harboured gastric giardiasis. All patients underwent upper gastrointestinal endoscopy because of dyspepsia, epigastric pain, or abdominal distension. Only two patients had diarrhoea at the time of investigation. Giardiasis was clinically unsuspected in all cases, although the nine patients who also had duodenal biopsies performed had concomitant intestinal giardiasis. Gastric giardiasis was invariably associated with chronic atrophic gastritis. Intestinal metaplasia of the gastric mucosa and Helicobacter pylori infection were found in 32 and 37 of the 41 patients with gastric giardiasis, respectively. CONCLUSIONS: The invariable association of gastric giardiasis with chronic atrophic gastritis, most often showing intestinal metaplasia and H pylori infection, indicates that a decreased gastric acidity is a prerequisite for localisation of G lamblia to the gastric mucosa. Though its possible role as a gastric pathogen remains to be elucidated, these findings suggest that trophozoites should be carefully searched for when examining gastric biopsy specimens showing chronic atrophic gastritis.

Adult

The outcome from acute subdural and epidural intracranial haematomas in very elderly patients.

Out of a consecutive series of 1082 operations performed on head-injured patients over a 9-year period, 28 cases of acute subdural haematomas (SDHs) or epidural haematomas (EDHs) occurring in patients aged between 80 and 100 years were selected. Mortality rates in these patients (100% in 2 EDHs, 88% in 26 SDHs) were significantly higher (p less than 0.01) compared with patients under 80 years (12% in 308 EDHs, 57% in 215 SDHs). Pre-existing diseases, primary events precipitating falls, and multiple system failure complicating the postoperative course accounted for most of the deaths. None of the patients operated upon with a Glasgow Coma Scale score of 11 or less survived. A typical 'talk and die' course occurred in two cases. Three patients, all operated on for SDH, survived and returned to their pre-injury conditions. It was concluded that, whilst the question as to whether to submit very old comatose patients to life-prolonging measures remains unsettled, there is a case for the prompt evacuation of extra-axial clots in patients with minimal impairment of consciousness.

Aged

Abnormal p53 expression in lung neuroendocrine tumors. Diagnostic and prognostic implications.

The diagnostic and prognostic implications of p53 immunostaining have been investigated in 59 pulmonary neuroendocrine tumors, including typical carcinoids (n = 15), so-called "atypical carcinoids" (n = 22), and small cell lung carcinomas (SCLCs; n = 22). Immunocytochemistry was performed on formalin-fixed, paraffin-embedded samples using the monoclonal antibody PAb1801, which has been shown to be suitable for staining fixed and embedded tissue sections. p53 immunoreactivity was restricted to atypical carcinoids (45% of the cases being immunoreactive) and to SCLCs (which were positively stained in 59% of the cases), whereas it was consistently lacking in typical carcinoid tumors. When the group of the so-called "atypical carcinoids" was further reclassified, p53 immunostaining was strictly confined to those cases belonging to the histologically more aggressive subsets (well differentiated neuroendocrine carcinoma subsets II and III). Within the same tumor type, however, p53 immunoreactivity did not correlate with the clinical outcome of the disease and was not predictive of the length of survival. The data indicate that abnormal p53 expression (which is strictly dependent on structural abnormalities of the p53 gene) is detectable in the majority of neuroendocrine carcinomas of the lung and might represent a useful adjunct in the differential diagnosis of pulmonary neuroendocrine neoplasms, particularly in routinely fixed and embedded small bronchoscopic biopsies.

Antibodies, Monoclonal

Non-radioactive nucleic acid probes: labelling and detection procedures.

A comprehensive overview is given concerning the in situ hybridization techniques using non-radioactively labelled probes. Details are given on the preparation of the probes with different reporter molecules and on the corresponding revealing assays. The development of non-isotopic labelling methods for nucleic acid probes has facilitated the diffusion of the in situ hybridization techniques to the research as well as to the clinical pathology laboratory. Non-radioactive probes have several advantages over the radiolabelled ones, including cost, shelf-life, safety and, last but not least, resolution of the signal.

2-Acetylaminofluorene

Glial fibrillary acidic protein immunoreactivity in normal and diseased human breast.

Immunostaining for glial fibrillary acidic protein (GFAP) identifies a minor subpopulation of immunoreactive myoepithelial cells in the normal resting human breast. The GFAP-immunoreactive cells also express a panel of myoepithelial cell markers, including cytokeratin 14 (CK 14), vimentin, smooth-muscle-specific actin isoforms, nerve growth factor receptor (NGFR) and common acute lymphoblastic leukaemia antigen (CALLA). The percentage of GFAP-immunoreactive myoepithelial cells is greatly increased in various neoplastic and non-neoplastic diseases of the breast, being highest in adenomyoepitheliomas. Furthermore, in all the instances of fibroadenoma, phyllodes tumour, epitheliosis and gynaecomastia, a variable number of epithelial cells also acquires immunoreactivity for GFAP, vimentin, CK 14, NGFR and, to a lesser extent, for CALLA. Conversely, GFAP immunoreactivity has never been encountered in the malignant cells of the different types of breast carcinoma. These findings suggest that the expression of GFAP might be a (possibly transient) feature of proliferating epithelial and myoepithelial cells in breast diseases other than carcinomas.

Actins

Idiotypic replica of an anti-human tumour-associated antigen monoclonal antibody. DNA sequence comparison between Ab1 and Ab3.

2G-3 is an anti-anti-idiotypic MoAb (Ab3) obtained upon immunization with a monoclonal Ab2 (A3B10), which behaves as the 'internal image' of CaMBr1, a saccharide epitope defined by MoAb MBr1 (Ab1). CaMBr1 is expressed on glycoconjugates of the human mammary carcinoma cell line MCF-7 and on normal and neoplastic mammary gland epithelial cells. Ab1 and Ab3, although exhibiting, in many respects, superimposable paratopic and idiotopic specificities, show a non-identical fine immunoreactivity, since 2G-3 has a preferential reactivity with the saccharidic epitope mounted on glycoproteins, while MBr1 reacts with both glycoproteins and glycolipids. V-region sequence analysis has shown that: (i) the VK genes employed belong to different families (VK1 and VK10); (ii) the JK2 segment is shared by the two L chains (thus a high degree of homology is observed between VK CDR3s); (iii) the VH genes employed derive from the same family VHIIB/J558 (but show CDR homology only in CDR2); (iv) different JH region genes are employed. These data, together with the comparison of deduced secondary structure parameters, give further evidence for the possible production of similar combining sites using different VH and VL germ-line genes.

Amino Acid Sequence

Deeply invasive squamous cell carcinoma of the conjunctiva: case report.

A 82-year-old man had a bulbar exophytic mass protruding through the lids and extending from the nasal side of the limbus to the caruncola in one eye. The lesion appeared 9 months before as a limbal nodule and showed a painless, slow evolution, ultimately leading to enucleation. The histopathologic examination of the neoplasm and eyeball showed an invasive squamous cell carcinoma of the conjunctiva which invaded the deep subepithelial tissue and reached the scleral surface. The evolution and pathologic features of this uncommon neoplasm were similar to that described in other cases previously reported. Such a clinical course is suggestive also of mucoepidermoid carcinoma of the conjunctiva, which closely resembles squamous cell carcinoma, but is more aggressive and locally invasive. However, after staining for mucin, this diagnosis was ruled out.

Aged

European multicentre study on melanoma immunoscintigraphy by means of 99mTc-labelled monoclonal antibody fragments. The European Multicentre Study Group.

A total of 493 melanoma patients were investigated by 20 European nuclear medicine departments by means of the same 99mTc-labelled immunoradiopharmaceutical and the same immunoscintigraphy (ISG) protocol. (i) No chemical or clinical toxicity was detected during or following the studies. (ii) Positive results were obtained in 287/363 (79%) patients (321 carrying known lesions and 42 carrying previously occult lesions): in 231 (80%) of them, 402/402 lesions were imaged; in the remaining 56 ISG-positive patients, 108/204 lesions were imaged; in 76 patients 0/122 lesions were imaged. (iii) The fraction of melanoma lesions visualized by ISG was 510/728 (70.1%); 605 of these lesions were already documented at the time of the study, and 123 were previously occult. (iv) A total of 218 documented melanoma lesions (30%) were not visualized by ISG in 132 patients: about 70% of the ISG-negative lesions were of small size (less than 2 cm diameter). (v) The melanoma nature of 69/123 previously occult lesions was confirmed by clinical criteria and/or additional investigations in follow-up studies. The results obtained in this study are similar to those obtained in the Italian Multicentre Study which had previously been carried out with 258 melanoma patients.

Antibodies, Monoclonal

Cytokeratin-immunoreactive cells of human lymph nodes and spleen in normal and pathological conditions. An immunocytochemical study.

The occurrence and the distribution of cytokeratin (CK)-immunoreactive reticulum cells in a series of normal and pathological human lymph nodes and spleens are documented. The immunoreactive cells exhibit morphological and immunophenotypic features of so-called fibroblastic reticulum cells, with or without myoid differentiation. They invariably co-express vimentin and, to a lesser extent, desmin and muscle-specific actin isoforms. These CK-immunoreactive cells are apparently a normal subpopulation of reticulum cells, being detectable from the early stages of spleen and lymph node development. They are distributed mainly in the paracortical and medullary regions of the lymph nodes and at the periphery of the white pulp in the spleen. Their number and distribution are highly variable in different neoplastic and non-neoplastic pathological conditions but the changes are not disease specific. CK-immunoreactive reticulum cells are easily identifiable in both frozen and fixed lymphoid tissue and in cytological smears of fine-needle aspirates, provided that monoclonal antibodies whose spectrum of reactivity includes cytokeratins 8 and 18 are used. The awareness of the occurrence of CK-immunoreactive cells in normal lymphoid tissues is of particular relevance in the search for micrometastatic foci using anti-CK antibodies.

Adult

Differences in the organization and chromosomal allocation of satellite DNA between the European long tailed house mice Mus domesticus and Mus musculus.

We compared the organization of satellite DNA (stDNA) and its chromosomal allocation in Mus domesticus and in Mus musculus. The two stDNAs show similar restriction fragment profiles after digestion (probed with M. domesticus stDNA) with some endonucleases of which restriction sequences are present in the 230-240 bp repetitive unit of the M. domesticus stDNA. In contrast, EcoRI digestion reveals that M. musculus stDNA lacks most of the GAATTC restriction sites, particularly at the level of the half-monomer. The chromosome distribution of stDNA (revealed by an M. domesticus stDNA probe) shows different patterns in the M. domesticus and M. musculus karyotypes, with about 60% of M. domesticus stDNA retained in the M. musculus genome. It is particularly noteworthy that the pericentromeric regions of M. musculus chromosomes 1 and X are totally devoid of M. domesticus stDNA sequences. In both groups, the differences in energy transfer between the stDNA-bound fluorochromes Hoechst 33258 and propidium iodide suggest that AT-rich repeated sequences have a much more clustered array in the M. domesticus stDNA, as if they are organized in tandem repeats longer than those of M. musculus. Considering the data as a whole, it seems likely that the evolutionary paths of the two stDNAs diverged after the generation of the ancestral 230-240 bp stDNA repetitive unit through the amplification, in the M. domesticus genome, of a family repeat which included the EcoRI GAATTC restriction sequence.

Animals

Adult nephroblastoma induced erythrocytosis. Report of a case and review of the literature.

We report a 32-year-old white male with nephroblastoma induced erythrocytosis. Serum erythropoietin levels were elevated preoperatively and normalized after surgical eradication of the renal mass causing the complete disappearance of the erythrocytosis. The erythropoietic hormone was demonstrated in the neoplastic mass confirming the nephroblastoma as the site of hormone synthesis. After surgery, the patient underwent a course of chemotherapy with actinomycin D (AMD) and vincristine (VCR) and is currently free of disease.

Adult

Long-term follow-up of the surgical treatment of intracranial coenurosis.

Intracranial infestation by the coenurus of the tapeworm Taenia multiceps is a rare occurrence in humans, with about 55 cases having been reported so far. Although most of these cases were observed in African or South American countries, the illness was occassionally found also in sheep-raising areas of Western Europe and the United States. Out of 4 personal cases, who were operated upon over an 18-year-period, 2 were neurologically intact respectively 20 and 3 years following surgical treatment. CT scans confirmed the absence of a progression of the disease. One patient was able to work 6 years after surgery, when he was killed in a road accident. A further, severely impaired patient remained unchanged and died with intercurrent infection 10 years following the operation.

Adult