Preclinical efficacy of carfilzomib in BRAF-mutant colorectal cancer models.

Serine/threonine-protein kinase B-raf (BRAF) mutations are found in 8-15% of colorectal cancer patients and identify a subset of tumors with poor outcome in the metastatic setting. We have previously reported that BRAF-mutant human cells display a high rate of protein production, causing proteotoxic stress, and are selectively sensitive to the proteasome inhibitors bortezomib and carfilzomib. In this work, we tested whether carfilzomib could restrain the growth of BRAF-mutant colorectal tumors not only by targeting cancer cells directly, but also by promoting an immune-mediated antitumor response.

Exploring circular MET RNA as a potential biomarker in tumors exhibiting high MET activity.

Background: MET-driven acquired resistance is emerging with unanticipated frequency in patients relapsing upon molecular therapy treatments. However, the determination of MET amplification remains challenging using both standard and next-generation sequencing-based methodologies. Liquid biopsy is an effective, non-invasive approach to define cancer genomic profiles, track tumor evolution over time, monitor treatment response and detect molecular resistance in advance.

Investigation into the Use of Encorafenib to Develop Potential PROTACs Directed against BRAF Protein.

BRAF is a serine/threonine kinase frequently mutated in human cancers. BRAF mutated protein is targeted through the use of kinase inhibitors which are approved for the treatment of melanoma; however, their long-term efficacy is hampered by resistance mechanisms. The PROTAC-induced degradation of BRAF has been proposed as an alternative strategy to avoid the onset of resistance.

Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair-Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy.

Targeted therapies, chemotherapy, and immunotherapy are used to treat patients with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer. The clinical effectiveness of targeted therapy and chemotherapy is limited by resistance and drug toxicities, and about half of patients receiving immunotherapy have disease that is refractory to immune checkpoint inhibitors. Loss of Werner syndrome ATP-dependent helicase (WRN) is a synthetic lethality in dMMR/MSI-H cells.

Survival rates of advanced estrogen-receptor positive breast cancer. Analysis of 211 cases.

Background: About 80% of breast cancer (BC) cases express estrogen receptor (ER), which has been correlated with good prognosis and response to estrogen deprivation Aim: To characterize ER positive advanced BC (ABC) patients treated at our institution assessing the impact of clinical pre-sentation (stage IV, de novo disease at diagnosis versus systemic recurrence) and BC subtype on survival rates.

Material And Methods: We evaluated 211 ER+ advanced BC (ABC) patients, treated between 1997 and 2017.

Results: The median overall survival (OS) was 37 months.

[Clinicopathological correlation among proliferative classes and subclasses of lupus nephritis in renal biopsies].

Background Lupus nephritis (LN) is a complication of systemic lupus erythematosus that requires renal biopsy (RB). Proliferative classes III, IV-S, IV-G have especial clinical and pathological characteristics. Aim To determine the association between pathological features in RB with serum creatinine and urine protein levels.

Mammography correlates to better survival rates in breast cancer patients: a 20-year experience in a University health institution.

Breast cancer (BC) is the most common malignancy in women. We retrieved medical records from >2,000 Chilean BC patients over the 1997-2018 period. The objective was to assess changes in clinical presentation or prognosis of our patients throughout these 20 years of practice.

Pseudodematiaceous Fungi in Rhinosinusal Biopsies: Report of 2 Cases With Light and Electron Microscopy Analysis.

The diagnosis of a mycosis is often established through a biopsy, which allows to differentiate invasive and non-invasive lesions, and also to identify hyaline and dematiaceous fungi. However, pigmented fungal elements that do not correspond to dematiaceous fungi, which we have called pseudodematiaceous, can occasionally be present in biopsies. Herein, we present 2 cases of mycosis caused by pseudodematiaceous fungi in rhinosinusal biopsies.

The Neutrophil to Lymphocyte Ratio Predicts the Response to Neoadjuvant Chemotherapy in Luminal B Breast Cancer.

Objective: Tumor response to neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients is a predictor for overall survival. The aim of our study was to determine a relationship between the neutrophil to lymphocyte ratio (NLR) prior to NAC, BC subtypes and the probability of a pathologic complete response (pCR). Materials and Methods: Medical records were collected retrospectively from Centro de Cancer at Red Salud UC-Christus.

[Support of the laboratory of microbiology and pathological anatomy in the diagnosis and management of infections in cancer patients and transplantation of hematopoietic stem cell transplant receptors].

The confrontation of the differential and etiological diagnosis of the infectious diseases of cancer patients, including hematopoietic stem cells transplant (HSCT) recipients, must correspond to an informed, timely decision that directly affects medical behavior that determines a better survival and quality of life for patients. The main goal of this work was to contribute to the management of these patients developing a useful tool for the clinician to make these decisions. For that, infections were grouped by compromised systems, differentiating the possible etiological agents in bacteria, viruses, fungi and parasites, highlighting the relevant diagnostic tests, mentioning the recommended techniques together with the optimal sample type for proper processing.

Surgical treatment in oligometastatic breast cancer.

Metastatic breast cancer (MBC) management is based on systemic treatment (ST), while the local therapy role remains controversial. We present the case of a 36-year-old woman with a diagnosis of hormone receptor-positive and human epidermal growth factor receptor type 2-positive breast cancer and isolated sternal metastasis, who received neoadjuvant ST with complete remission and later primary tumour surgery. Oligometastatic patients are a subgroup of MBC that can benefit from aggressive local therapies, even with curative intent.

Breast lesions with atypia in percutaneous biopsies, managed with surgery in the last 10 years.

Introduction: The optimal management of breast lesions with atypia (BLA), detected in percutaneous biopsies after screening mammograms, is a controversial issue. The aim of this paper is to compare histological diagnosis by percutaneous biopsy with the results of the surgical biopsy of these lesions and to analyse the changes to clinical approach this would imply.

Method: A retrospective study was carried out on patients operated on between June 2007 and June 2017 with a diagnosis of BLA.

Granulomatous lobular mastitis associated with ductal carcinoma in situ of the breast.

The association of granulomatous lobular mastitis and carcinoma of the breast is very infrequent. We present the case of a 44-year-old woman with concurrent granulomatous lobular mastitis with coryneform bacteria and ductal carcinoma in situ in the same breast.

[Survival of patients with advanced HER2+ breast cancer. Analysis of a cancer center database].

Background: HER2+ breast cancer (BC) subtype overexpresses the Human Epidermal growth factor Receptor type-2 (HER2) and is characterized by its aggressiveness and its high sensitivity to monoclonal antibody-based HER2-targeted therapies.

Aim: To assess the prognosis and evaluate the impact of novel anti-HER2 therapies on advanced HER2+ BC patients treated at our institution over the last decades.

Material And Methods: Analysis of the patient database at a cancer center of a university hospital.

Coryneform Bacteria in Granulomatous Lobular Mastitis: Morphological Diagnosis in Breast Biopsies.

Granulomatous lobular mastitis is a rare disease whose origin is still unknown and shows an increase in its frequency. Morphological, microbiological, and molecular biology studies have linked this disease to lipophilic and fastidious corynebacteria, suggesting its possible infectious etiology. This series describes and reviews in detail the distinctive morphological characteristics of the bacteria present in the granulomas of this disease, the usefulness of histochemical techniques for their identification, and our proposal for a tissue quantification score for the bacteria.

Reliance upon ancestral mutations is maintained in colorectal cancers that heterogeneously evolve during targeted therapies.

Attempts at eradicating metastatic cancers with targeted therapies are limited by the emergence of resistant subclones bearing heterogeneous (epi)genetic changes. We used colorectal cancer (CRC) to test the hypothesis that interfering with an ancestral oncogenic event shared by all the malignant cells (such as WNT pathway alterations) could override heterogeneous mechanisms of acquired drug resistance. Here, we report that in CRC-resistant cell populations, phylogenetic analysis uncovers a complex subclonal architecture, indicating parallel evolution of multiple independent cellular lineages.

Bromodomain inhibition exerts its therapeutic potential in malignant pleural mesothelioma by promoting immunogenic cell death and changing the tumor immune-environment.

Systemic treatment of malignant pleural mesothelioma (MPM) is moderately active for the intrinsic pharmacological resistance of MPM cell and its ability to induce an immune suppressive environment. Here we showed that the expression of bromodomain (BRD) proteins and was significantly higher in human primary MPM cells compared to normal mesothelial cells (HMC). Nanomolar concentrations of bromodomain inhibitors (BBIs) JQ1 or OTX015 impaired patient-derived MPM cell proliferation and induced cell-cycle arrest without affecting apoptosis.

Can Histological Grade and Mitotic Index Replace Ki67 to Determine Luminal Breast Cancer Subtypes?

Introduction: Breast cancer can be classified into subtypes based on immunohistochemical markers, with Ki67 expression levels being used to divide luminal BC tumors in luminal A and B subtypes; however, Ki67 is not routinely determined due to a lack of standardization. Objective: To evaluate histological grade and Eliminate: the mitotic index to determine if they can be used as an alternative method to Ki67 staining for luminal subtype definition. Methods: We evaluated estrogen receptor positive breast cancer tissue samples.

Discovery of methylated circulating DNA biomarkers for comprehensive non-invasive monitoring of treatment response in metastatic colorectal cancer.

Objective: Mutations in cell-free circulating DNA (cfDNA) have been studied for tracking disease relapse in colorectal cancer (CRC). This approach requires personalised assay design due to the lack of universally mutated genes. In contrast, early methylation alterations are restricted to defined genomic loci allowing comprehensive assay design for population studies.

Emergence of MET hyper-amplification at progression to MET and BRAF inhibition in colorectal cancer.

Background: Combined MET and BRAF inhibition showed clinical benefit in a patient with rectal cancer carrying BRAF and MET amplification. However after 4 months, acquired resistance emerged and the patient deceased shortly after disease progression. The mechanism of resistance to this drug combination is unknown.

Nephrotic syndrome due to minimal change disease secondary to spider bite: clinico-pathological case of a non-described complication of latrodectism.

The patient was an 18-year-old man who developed nephrotic syndrome after a 'wheat spider' bite (). Due to this atypical manifestation of latrodectism, a renal biopsy was performed showing minimal change disease. The nephrotic syndrome subsided after 1 week without specific treatment.

Clinico-Pathologic Subtypes of Breast Cancer Primary Tumors Are Related to Prognosis after Recurrence.

Background: Pathological factors, based mainly on immunohistochemistry (IHC) and histological differentiation, are mostly used to differentiate breast cancer (BC) subtypes. Our present aim was to describe the characteristics and survival of a relapsing BC patient cohort based on clinico-pathologic subtypes determined for the primary tumors. Methods: We used a clinico- pathological definition of BC subtypes based on histological grade (HG), estrogen receptor (ER), progesterone receptor (PgR),and epidermal growth factor receptor type 2 (HER2) expression assessed by IHC.