Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.

HER2-positive (HER2) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2 mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions.

Recurrent herpes simplex virus mimicking vulvar carcinoma in patient with Human Immunodeficiency Virus: A case report.

Patients with human immunodeficiency virus (HIV) are at increased risk for developing other gynecologic conditions, including herpes simplex virus (HSV) and vulvar intraepithelial neoplasia (VIN)/carcinoma. We describe the case of a woman with a history of microinvasive vulvar squamous cell carcinoma who presented with hypertrophic ulcerated vulvar and -anal masses concerning for malignancy. This case highlights the need to maintain a high index of suspicion for malignancy and herpes simplex virus, even with negative polymerase chain reaction (PCR) test, as well as the difficulty of treating this often-resistant lesion.

The pathological and clinical landscape of refractory metastatic triple negative breast cancer: a narrative review.

Background And Objective: Triple negative breast cancer (TNBC) refers to a special subtype of breast cancer that is negative for the estrogen receptor, the progesterone receptors, and human epidermal growth factor receptor 2. As a group of diseases, it has strong heterogeneity. Refractory metastatic triple negative breast cancer (mTNBC) has even greater heterogeneity, more susceptibility to drug resistance, and faster progression, which makes it more difficult to treat effectively and significantly reduces a patient's overall survival.

Age at initial diagnosis and prognosis of breast cancer: a nationwide multicenter retrospective study in China.

Background: Several studies have indicated possible associations between age and the prognosis of breast cancer (BC), but limited data are available from hospital-based multicenter studies in China. This study aimed to explore the associations between age at initial diagnosis of BC and the risk of recurrence or metastasis among Chinese women with newly diagnosed advanced breast cancer (ABC) and provide treatment decision support for BC patients of different ages to medical workers.

Methods: The medical records of patients newly diagnosed with ABC were obtained from 21 hospitals in seven geographic regions in China from 2012 to 2014.

GLI1 -Rearranged Enteric Tumor : Expanding the Spectrum of Gastrointestinal Neoplasms With GLI1 Gene Fusions.

GLI1 encodes a transcription factor that targets cell cycle regulators affecting stem cell proliferation. GLI1 gene fusions were initially described in pericytomas with a t[7;12] translocation and more recently in gastric plexiform fibromyxomas and gastroblastomas. This study describes the clinicopathologic, immunohistochemical, and molecular features of three intestinal-based neoplasms harboring GLI1 gene fusions.

Effect of breast-conserving surgery plus radiotherapy versus mastectomy on breast cancer-specific survival for early-stage contralateral breast cancer.

Background: Breast-conserving surgery followed by radiotherapy is recommended in most women with early-stage unilateral breast cancer. However, its role in contralateral breast cancer (CBC) patients remains unclear. This retrospective study aimed to evaluate the breast cancer-specific survival (BCSS) outcomes after breast-conserving surgery plus radiotherapy compared with mastectomy in women with early-stage (T1-2N0-1M0) CBC.

Comparisons of Treatment for HER2-Positive Breast Cancer between Chinese and International Practice: A Nationwide Multicenter Epidemiological Study from China.

Objective: To better understand the status of medical treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the differences between the Chinese and the international clinical practice.

Methods: This was a retrospective, nationwide, multicenter, epidemiological study of advanced breast cancer patients from China. Between January 01, 2012, and December 31, 2014, a total of 3649 patients, covering 7 geographic regions and 21 institutions, participated in this series of studies.

MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study.

Aim: To compare the efficacy, safety, and tolerability of abemaciclib plus endocrine therapy (ET) ET alone in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from China, Brazil, India, and South Africa.

Methods: This randomized, double-blind, phase III study was conducted between 9 December 2016 and 29 March 2019. Postmenopausal women with HR-positive, HER2-negative ABC with no prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) received abemaciclib (150 mg twice daily) or placebo plus: anastrozole (1 mg/day) or letrozole (2.

Docetaxel-Loaded Chitosan-Cholesterol Conjugate-Based Self-Assembled Nanoparticles for Overcoming Multidrug Resistance in Cancer Cells.

Cholesteryl hemisuccinate (CHS)-conjugated chitosan (CS)-based self-assembled nanoparticles (NPs) were developed for enhancing the intracellular uptake of docetaxel in multidrug resistance (MDR)-acquired cancer cells. CHS-CS was successfully synthesized and self-aggregation, particle size, zeta potential, drug entrapment efficiency, and in vitro drug release of docetaxel-loaded CHS-CS NPs were tested. The optimized NPs had a mean hydrodynamic diameter of 303 nm, positive zeta potential of 21.

Profile and outcome of receptor conversion in breast cancer metastases: a nation-wide multicenter epidemiological study.

Although receptor status including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) of the primary breast tumors was related to the prognosis of breast cancer patients, little information is yet available on whether patient management and survival are impacted by receptor conversion in breast cancer metastases. Using data from the nation-wide multicenter clinical epidemiology study of advanced breast cancer in China (NCT03047889), we report the situation of retesting ER, PR and HER2 status for breast cancer metastases and evaluate the patient management and prognostic value of receptor conversion. In total, 3295 patients were analyzed and 1583 (48.

Small nucleolar host gene 6 promotes esophageal squamous cell carcinoma cell proliferation and inhibits cell apoptosis.

Esophageal cancer (ESCC) is one of the most common causes of cancer-associated mortality in China. The present investigation reveals that non-coding RNAs (ncRNAs), including long ncRNAs (lncRNAs), exert a significant effect on the initiation, development and metastasis of malignant tumors, including ESCC. However, to the best of our knowledge, the function of non-protein-coding genes that host small nucleolar RNAs has not been investigated in cancer, particularly in ESCC.

Glycogenic hepatopathy: A narrative review.

Glycogenic hepatopathy (GH) is a rare complication of the poorly controlled diabetes mellitus characterized by the transient liver dysfunction with elevated liver enzymes and associated hepatomegaly caused by the reversible accumulation of excess glycogen in the hepatocytes. It is predominantly seen in patients with longstanding type 1 diabetes mellitus and rarely reported in association with type 2 diabetes mellitus. Although it was first observed in the pediatric population, since then, it has been reported in adolescents and adults with or without ketoacidosis.

Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial.

Background: Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer.

Methods: For this open-label, randomised, phase 3, hybrid-designed trial undertaken at 12 institutions or hospitals in China, we included Chinese patients aged 18-70 years with previously untreated, histologically confirmed metastatic triple-negative breast cancer, and an ECOG performance status of 0-1.

Clinical significance of CD44s, CD44v3 and CD44v6 in breast cancer.

Objectives: To evaluate levels of CD44 standard variant (CD44s), CD44 variant exon 3 (CD44v3) and CD44 variant exon 6 (CD44v6) protein in breast cancer tissue, and investigate their relationships with clinicopathological characteristics of the disease.

Methods: Immunohistochemistry for CD44s, CD44v3 and CD44v6 was retrospectively performed on formalin-fixed paraffin wax-embedded breast cancer tissue samples.

Results: Tumour tissue samples from 60 patients with breast cancer were included.

MLH1 polymorphisms and cancer risk: a meta-analysis based on 33 case-control studies.

Objective: Cumulative evidence suggests that MLH1, the key component in the mismatch pathway, plays an important role in human cancers. Two potential functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in cancer risk. The aim of this meta-analysis was to summarize the evidence for associations.

Genetic variants of NBS1 predict clinical outcome of platinum-based chemotherapy in advanced non-small cell lung cancer in Chinese.

Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy.

Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients.

Regulation of CD44 expression by tumor necrosis factor-α and its potential role in breast cancer cell migration.

CD44 molecule plays critical role in distant malignant metastasis. It is expressed in standard form (CD44s) or variant form (CD44v). Tumor necrosis factor-α (TNF-α) is highly expressed in the cancer microenvironment.

[Expression of HER-2 and leptin in gastric cancer and their clinical significance].

Objective: To assess the expression of HER-2 and leptin in gastric cancer and evaluate their relationship with VEGF expression and clinicopathological features, and their prognostic value for gastric cancer patients.

Methods: One hundred and ten gastric cancer specimens and the corresponding metastatic lymph nodes were detected for HER-2 by immunohistochemistry (IHC). All primary cancer tissues were detected for leptin, OB-Rb and VEGF.

Overexpression of polo-like kinase 1 and its clinical significance in human non-small cell lung cancer.

Polo-like kinase 1 is a serine/threonine kinase which plays an essential role in mitosis and malignant transformation. The aim of this study was to investigate the prognostic significance of polo-like kinase 1 expression and determine its possibility as a therapeutic target in non-small cell lung cancer. Semi-quantitative RT-PCR assay was performed to detect polo-like kinase 1 mRNA expression in non-small cell lung cancer cells or tissues.

Expression and clinical significance of leptin, the functional receptor of leptin (OB-Rb) and HER-2 in non-small-cell lung cancer: a retrospective analysis.

Background: The human epidermal growth factor receptor 2 (HER-2) and leptin/OB-R system have been reported to be intertwined in several cancer types. However, limited research has been conducted with regard to this interaction in lung cancers. In this study, we investigated the relationship between the expression levels of these proteins and the development, progression and prognosis of non-small-cell lung cancer (NSCLC).

MicroRNA-21 modulates chemosensitivity of breast cancer cells to doxorubicin by targeting PTEN.

Background And Aims: Ovexpression of microRNA-21 (miR-21) is found in various human cancers. Our aim is to investigate the association of miR-21 expression with the sensitivity of breast cancer cells to doxorubicin (ADR).

Methods: The half maximal inhibitory concentration (IC(50)) value of ADR in resistant MCF-7/ADR or parental MCF-7 cells was determined by MTT assay.

The regimen of gemcitabine and cisplatin combined with radio frequency hyperthermia for advanced non-small cell lung cancer: a phase II study.

Purpose: This phase II randomised trial was designed to evaluate the therapeutic efficacy and feasibility of radio frequency regional hyperthermia in combination with chemotherapy for patients with advanced non-small lung cancer (NSCLC).

Methods: Eighty patients with pathologically proven advanced NSCLC, were enrolled and divided into two groups. Group A patients were treated by radio frequency regional hyperthermia in combination with the regimen of gemcitabine and cisplatin (GP).

First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer.

Background: Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK) inhibitor of epidermal growth factor receptor (EGFR), displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC) in Chinese population are not sufficient.