A Case of COL1A1-PDGFB Fusion Uterine Sarcoma.

COL1A1-PDGFB gene fusion uterine sarcoma is a recently described entity which shows some overlapping features with dermatofibrosarcoma protuberans. To date, only 4 cases have been reported in the literature. Due to its rarity, succinct clinicopathologic characteristics are yet to be established. We report a fifth case initially mistaken as a uterine fibroid which histologically proved to be a CD34 + high-grade spindle cell proliferation which on fluorescence in situ hybridization analysis displayed COL1A1-PDGFB gene rearrangement. With this case description we hope to raise awareness and aid in the characterization of this emerging entity.

Mechanistic added value of a trans-Sulfonamide-Platinum-Complex in human melanoma cell lines and synergism with cis-Platin.

BACKGROUND: Cisplatin is a potent antitumor agent. However, toxicity and primary and secondary resistance are major limitations of cisplatin-based chemotherapy, leading to therapeutic failure. We have previously reported that mono-sulfonamide platinum complexes have good antitumor activity against different tumoral cell lines and with a different and better cytotoxic profile than cisplatin. Besides, N-sulfonamides have been used extensively in medicinal chemistry as bactericides, anticonvulsant, inhibitors of the carbonic anhydrase, inhibitors of histone deacetylases, and inhibitors of microtubule polymerization, among others. METHODS: We aimed to compare the cytotoxic effects of cisplatin and a trans-sulfonamide-platinum-complex (TSPC), in two human melanoma cell lines that differ in their TP53 status: SK-MEL-5, TP53 wild type, and SK-MEL-28, TP53 mutated. We performed cytotoxicity assays with both drugs, alone and in combination, cell cycle analyses, western blotting and immunoprecipitation, and fluorescence immunocytochemistry. RESULTS: TSPC had similar antiproliferative activity than cisplatin against SK-MEL-5 (3.24 ± 1.08 vs 2.89 ± 1.12 µM) and higher against SK-MEL-28 cells (5.83 ± 1.06 vs 10.17 ± 1.29 µM). Combination of both drugs inhibited proliferation in both cell lines, being especially important in SK-MEL-28, and showing a synergistic effect. In contrast to cisplatin, TSPC caused G1 instead G2/M arrest in both cell lines. Our present findings indicate that the G1 arrest is associated with the induction of CDKN1A and CDKN1B proteins, and that this response is also present in melanoma cells containing TP53 mutated. Also, strong accumulation of CDKN1A and CDKN1B in cells nuclei was seen upon TSPC treatment in both cell lines. CONCLUSIONS: Overall, these findings provide a new promising TSPC compound with in vitro antitumor activity against melanoma cell lines, and with a different mechanism of action from that of cisplatin. Besides, TSPC synergism with cisplatin facilitates its potential use for co-treatment to reduce toxicity and resistance against cisplatin. TSPC remains a promising lead compound for the generation of novel antineoplastic agent and to explore its synergism with other DNA damaging agents.

Digging into phenotype change in mismatch repair deficient endometrial carcinoma and treatment with immune checkpoint inhibition, a case report.

•False negative cases for mismatch repair determination by immunohistochemistry may occur.•The mismatch repair phenotype in endometrial carcinoma impacts on therapeutic decision making.•Retesting for mismatch repair at relapse of endometrial carcinoma should be considered.

Prevalence of Anal High-Risk Human Papilloma Virus Infection and Abnormal Anal Cytology among Women Living with HIV.

Background: Women living with human immunodeficiency virus (HIV), WLWHs, are at high risk of developing anal cancer associated with high-risk human papilloma virus infection (HR-HPV). We analyzed the prevalence of anal HR-HPV infection and abnormal anal cytology in a cohort of WLWHs and assessed the risk factors for anal HR-HPV infection. Methods: We present a single-center, observational cross-sectional study. WLWHs who underwent anal cytology and anal human papilloma virus (HPV) testing were selected. High-resolution anoscopy was performed in cases of abnormal anal cytology. All suspicious lesions were biopsied. A univariate and multivariate logistic regression model was used to analyze risk factors for abnormal anal screening. The results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Results: In total, 400 WLWHs were studied. Of them, 334 met the eligibility criteria and were enrolled in the study. Abnormal anal cytology was detected in 39.5% of patients, and anal HR-HPV in 40.1%, with HPV 16 in 33 (26.6%) of them. Concomitant HR-HPV cervical infection was the only independent risk factor for HR-HPV anal infection (OR 1.67 95% CI, p < 0.001). Conclusions: WLWHs have a high prevalence of HR-HPV anal infection and anal cytologic abnormalities. HR-HPV cervical infection is the main predictor of HR-HPV anal infection.

New case of secondary bladder amyloidosis with massive hematuria-role of intravesical instillations with dimethyl sulfoxide.

Secondary bladder amyloidosis is a rare condition with less than 60 cases published in the world. It is usually secondary to chronic inflammatory processes such as rheumatologic diseases. Hematuria is its predominant and most important symptom, and usually occurs after a bladder catheterization. The diagnostic confirmation is made through a pathological and immunohistochemical study. The treatment must be staggered from less to more invasive. Our objectives are to present a new case of secondary bladder amyloidosis in a woman with a history of chronic bronchiectasis after tuberculosis and frequent super infections, whose main manifestation was a massive hematuria, and review this rare pathology. We have obtained very good initial results using intravesical instillations with dimethyl sulfoxide (DMSO) with complete resolution of the hematuria, the patient remaining asymptomatic for 6 months. After that, there was a recurrence of the hematuria that was treated with embolization of the hypogastric arteries, with good results. We can conclude that, despite being a rare condition, we must consider secondary bladder amyloidosis in patients who have already been diagnosed with systemic amyloidosis and/or chronic pathologies who develop hematuria after bladder catheterization. Based on our experience, instillations with dimethyl sulfoxide are a safe option and provide a quick and temporary resolution of hematuria symptoms.

Multiplatform plasma fingerprinting in cancer cachexia: a pilot observational and translational study.

BACKGROUND: Cachexia is a metabolic syndrome that affects up to 50-80% of cancer patients. The pathophysiology is characterized by a variable combination of reduced food intake and abnormal metabolism, including systemic inflammation and negative protein and energy balance. Despite its high clinical significance, defined diagnostic criteria and established therapeutic strategies are lacking. The 'omics' technologies provide a global view of biological systems. We hypothesize that blood-based metabolomics might identify findings in cachectic patients that could provide clues to gain knowledge on its pathophysiology, and eventually postulate new therapeutic strategies. METHODS: This is a cross-sectional observational study in two cohorts of cancer patients, with and without cachexia. Patients were consecutively recruited from routine clinical practice of a General Oncology Department at '12 de Octubre' University Hospital. Selected clinical and biochemical features were collected. Blood metabolite fingerprinting was performed using three analytical platforms, gas chromatography coupled to mass spectrometry (GC-MS), capillary electrophoresis coupled to mass spectrometry (CE-MS), and liquid chromatography coupled to mass spectrometry (LC-MS). Besides, we performed pathway-based metabolite analyses to obtain more information on biological functions. RESULTS: A total of 15 subjects were included in this study, 8 cachectic and 7 non-cachectic patients. Metabolomic analyses were able to correctly classify their samples in 80% (GC-MS), 97% (CE-MS), 96% [LC-MS (positive mode)], and 89% [LC-MS (negative mode)] of the cases. The most prominent metabolic alteration in plasma of cachectic patients was the decrease of amino acids and derivatives [especially arginine, tryptophan, indolelactic acid, and threonine, with 0.4-fold change (FC) compared with non-cachectic patients], along with the reduction of glycerophospholipids [mainly lysophosphatidylcholines(O-16:0) and lysophosphatidylcholines(20:3) sn-1, FC = 0.1] and sphingolipids [SM(d30:0), FC = 0.5]. The metabolite with the highest increase was cortisol (FC = 1.6). Such alterations suggest a role of the following metabolic pathways in the pathophysiology of cancer cachexia: arginine and proline metabolism; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; lysine degradation; aminoacyl-tRNA biosynthesis; fatty acid elongation in mitochondria; tricarboxylic acids cycle; among others. CONCLUSIONS: These findings suggest that plasma amino acids and lipids profiling has great potential to find the mechanisms involved in the pathogenesis of cachexia. Metabolic profiling of plasma from cancer patients show differences between cachexia and non-cachexia in amino acids and lipids that might be related to mechanisms involved in its pathophysiology. A better understanding of these mechanisms might identify novel therapeutic approaches to palliate this unmet medical condition.