HIV-Associated Genital Immune Biomarkers in the Female Sex Worker Population: A Pilot Study.

Problem: Female sex workers (FSW) experience a disproportionately high burden of HIV infection, yet characterization of the vaginal immune microenvironment that may impact biological risk is not well studied among FSW in the United States. Additionally, feasible methodology for collecting biological materials has not been evaluated in this population.

Methods: We enrolled 10 FSW (5 premenopausal, 5 postmenopausal) who participated in a survey and provided vaginal swabs.

Effect of progestin-based contraceptives on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls.

Adolescent girls bear a disproportionate burden of both the HIV epidemic and unintended pregnancies; yet important questions remain unanswered regarding the effects of hormonal contraceptives on the vaginal immune microenvironment, which can impact HIV susceptibility in this group. Multiple studies report genital immune alterations associated with the progestin-based contraceptive Depot medroxyprogesterone acetate (DMPA) in adult women, but there is little available data in adolescents. The objective of this longitudinal cohort study was to evaluate the effects of short-term use of three progestin-based contraceptives, levonorgestrel intrauterine device (LNG-IUD), subdermal etonogestrel (ETNG), and injectable DMPA, on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls.

Validation of Inflammatory Prognostic Biomarkers in Pleural Mesothelioma.

Evoked from asbestos-induced inflammation, pleural mesothelioma represents a fatal diagnosis. Therapy ranges from nihilism to aggressive multimodality regimens. However, it is still unclear who ultimately benefits from which treatment.

Clinical score for colorectal cancer patients with lung-limited metastases undergoing surgical resection: Meta-Lung Score.

Background: Radical resection of isolated lung metastases (LM) from colorectal cancer (CRC) is debated. Like Fong's criteria in liver metastases, our study was meant to assign a clinical prognostic score in patients with LM from CRC, aiming for better surgery selection.

Methods: We retrospectively analyzed data from 260 CRC patients who underwent curative LM resection from December 2002 to January 2022, verifying the impact of different clinicopathological features on the overall survival (OS).

Designing effective anticancer-radiopeptides. A Molecular Dynamics study of their interaction with model tumor and healthy cell membranes.

One of the greatest merit of the use of radiopeptides in oncology is their selectivity which, however, brings about the drawback that each radiopeptide is specific for a given tumor type. To overcome this problem the direction currently taken in drug design is that of radiolabelling peptide hormones (or their analogues), relying on their intrinsic ability to bind to specific receptors in precise areas of the human body, at the cost, however, of a poor selectivity against healthy cells. We present here an extensive Molecular Dynamics study of a promising alternative inspired by the mechanism through which antimicrobial peptides interact with the negatively charged bacterial membranes.

Benefits of oxytocin administration in obstructive sleep apnea.

Activation of oxytocin receptors has shown benefits in animal models of obstructive sleep apnea (OSA). We tested if nocturnal oxytocin administration could have beneficial effects in OSA patients. Eight patients diagnosed with OSA were administered intranasal oxytocin (40 IU).

Hereditary nonpolyposis colorectal cancer: an approach to the selection of candidates to genetic testing based on clinical and molecular characteristics.

Objective: Identification of clinical and molecular characteristics associated with constitutional MLH1 and MSH2 mutations and definition of a stepwise strategy for the selection of colorectal cancer (CRC) patients amenable to MLH1 and MSH2 genetic testing.

Methods: 90 unrelated CRC patients were initially selected on the basis of either familial or early onset occurrence of CRC. They were screened for the presence of constitutional MLH1 and MSH2 mutations and for microsatellite instability (MSI).

Microsatellite instability and MLH1 and MSH2 germline defects are related to clinicopathological features in sporadic colorectal cancer.

Clinical and pathological features were evaluated to predict tumor microsatellite instability (MSI) and germline mutations in MLH1 and MSH2 DNA mismatch repair genes in two patient groups with sporadic colorectal cancer (CRC): 38 young patients (age /=60 years). Nine (25.7%) young patients out of 35 and five (16%) old patients out of 31 exhibited MSI in their cancers.

Evaluation of the replication error phenotype in relation to molecular and clinicopathological features in hereditary and early onset colorectal cancer.

Mutations affecting human mismatch repair (MMR) genes (MLH1, MSH2, PMS1, PMS2, and MSH6) cause tumour predisposition in hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, and an association has been demonstrated with the replication error (RER) phenotype in most colorectal and some extracolonic neoplasms. A pathogenetic model for RER+ tumours through inactivation of suppressor genes has been hypothesised, and TGF beta RII, BAX and IGFIIR genes have recently been proposed as targets of such inactivating mutations. In this study, a series of 47 tumours developed in patients with known MLH1/MSH2 status and a family history of HNPCC and/or early onset colorectal cancer were characterised for the RER phenotype through microsatellite analysis.

Hereditary colorectal cancer in the general population: from cancer registration to molecular diagnosis.

Background: Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common inherited disorders predisposing to cancer. The genes responsible for the disease have recently been cloned and characterised; their mutations induce a generalised genomic instability which is particularly evident at microsatellite loci (replication error (RER)+ phenotype).

Aims: To investigate how to select individuals and families in the general population who should be screened for constitutional mutations predisposing to colorectal cancer.

High prevalence of activated intraepithelial cytotoxic T lymphocytes and increased neoplastic cell apoptosis in colorectal carcinomas with microsatellite instability.

Microsatellite instability (MSI) characterizes colorectal carcinomas (CRCs) in hereditary nonpolyposis colorectal cancer (HNPCC) syndrome and a proportion of sporadic CRCs. These MSI+ CRCs share several clinicopathological features, including a reputation for better survival rates than MSI- cases and a pronounced stromal inflammatory reaction of still undefined nature. In the present study, the presence, spatial distribution, and activation status of infiltrating cytotoxic effectors were investigated comparatively in 18 MSI+ and 37 MSI- CRCs by immunohistochemistry.

Lack of PMS2 gene-truncating mutations in patients with hereditary colorectal cancer.

Hereditary non-polyposis colorectal cancer (HNPCC) is a genetically heterogeneous disease for which PMS2 gene, a member of the human PMS gene family, is believed to have a marginal role. To better define the contribution of PMS2 to hereditary colorectal cancer, we investigated this gene in 22 unrelated Italian patients that, despite a positive family history and/or early onset and development of tumors with microsatellite instability (MSI), did not carry constitutional mutations of MLH1 and MSH2 genes. No mutations with clear-cut pathogenetic significance were detected in the coding regions of PMS2 gene, but only 8 polymorphisms (7 common and 1 rare, 3 silent and 5 missense) and 3 unique molecular variants (2 missense substitutions and one 3-nucleotide deletion) were seen.

MLH1 and MSH2 constitutional mutations in colorectal cancer families not meeting the standard criteria for hereditary nonpolyposis colorectal cancer.

Genetic diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) may have a significant impact on the clinical management of patients and their at-risk relatives. At present, clinical criteria represent the simplest and most useful method for the identification of HNPCC families and for the selection of candidates for genetic testing. However, reports of mismatch repair (MMR) gene mutations in families not fulfilling the minimal diagnostic criteria point out the necessity to identify additional clinical parameters suggestive of genetic predisposition to colorectal cancer (CRC) related to MMR defects.

Characterization of MLH1 and MSH2 alternative splicing and its relevance to molecular testing of colorectal cancer susceptibility.

The phenomenon of alternative splicing in the DNA mismatch repair genes MLH1 and MSH2 was extensively investigated by coupled reverse transcription-polymerase chain reaction in different human tissues, including 42 mononuclear blood cell samples--31 obtained from familial colon cancer patients or their at-risk relatives and 11 from healthy blood donors--7 normal colonic mucosae, 4 established human cancer cell lines, 8 colorectal tumors, and one sample each of ileum, liver, muscle, thymus, breast, and EBV-transformed lymphoblasts. Several isoforms were observed for each gene. Products of MLH1 alternative splicing included mRNAs lacking alternative exons 6/9, 9, 9/10, 9/10/11, 10/11, 12, 16, and 17.

Loss of heterozygosity at the 5,10-methylenetetrahydrofolate reductase locus in human ovarian carcinomas.

The high-affinity folate-binding protein (FBP) is primarily involved in the uptake of the 5-methyltetrahydrofolate, and its expression may be physiologically regulated by the intracellular folate content. The overexpression of FBP on the cell surface of ovarian carcinoma cells may be responsible for an increased folate uptake. We tested the hypothesis of the existence of a defect in the 5, 10-methylenetetrahydrofolate reductase (MTHFR) in ovarian tumours that could cause reduced intracellular regeneration of the 5-methyltetrahydrofolate and induce increased FBP expression.

Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer.

Mismatch repair genes MSH2 and MLH1 are considered to be the two major genes that are responsible for hereditary nonpolyposis colorectal cancer (HNPCC). Germline heterozygous inactivating mutations of MSH2 and MLH1 have been identified previously in a substantial fraction of individuals who are predisposed genetically to colorectal carcinoma (CRC) and other tumors of the HNPCC spectrum. With the aim of determining the relevance of these two genes in the Italian population, we submitted to mutational analysis a set of 17 HNPCC families, all of which fulfilled the "Amsterdam criteria.

Suppressive role of the metastasis-related nm23-H1 gene in human ovarian carcinomas: association of high messenger RNA expression with lack of lymph node metastasis.

The nm23-H1 gene has been proposed as a metastasis suppressor gene. It is located on the long arm of chromosome 17, which is frequently deleted in ovarian cancer, and shows altered expression and structure in some advanced neoplasms. To evaluate the role of nm23-H1 in ovarian carcinogenesis, we have analyzed this gene in 66 primary human ovarian carcinomas at both the DNA and RNA levels.

Molecular mechanisms possibly affecting WT1 function in human ovarian tumors.

The frequent allelic deletions observed on the short arm of chromosome 11 in ovarian tumors suggest that the WT1 gene, a proposed tumor-suppressor gene located on chromosome 11p13 and expressed in the human fetal genitourinary system, may contribute to the development of ovarian neoplasms. Structural and sequence analysis of the entire coding portions of the WT1 gene did not reveal any abnormalities in the 20 ovarian tumor specimens (13 of which showed 11p13 allelic deletions) and 5 cell lines which we analyzed. These findings invalidate the hypothesis that the WT1 gene functions as a classical tumor-suppressor gene in ovarian tumorigenesis and suggest that a different recessive oncogene may be "exposed" by the observed 11p13 allelic deletions.

[Influence of age on the short- and medium-term prognosis in patients with acute myocardial infarct].

Elderly patients with acute myocardial infarction (AMI) have a higher subsequent mortality than younger ones, yet the reasons for this adverse prognosis are poorly understood. We compared the clinical course and the prognosis of 163 patients aged 40 to 69 years with 112 patients older than 70 years. During hospitalization period 15.

[Ischemic coronary artery disease in menopause].

Women show a lower incidence of Coronary Artery Disease (CAD) and probably a better prognosis than men. However better survival rate of women tended to be obscured because they were more likely to have histories of hypertension and diabetes and to be older than men. In this paper, incidence, clinical presentation, and prognosis of CAD in women are examined.