Evaluation of diagnostic and predictive values of the serum VEGF-A level and systemic immune-inflammation index in small cell lung cancer.

Purpose: To evaluate diagnostic and predictive values of the serum vascular endothelial growth factor-A (VEGF-A) level and systemic immune-inflammation index (SII) in small cell lung cancer (SCLC) patients. Methods: From January 2018 to April 2020, we prospectively enrolled 59 untreated SCLC patients in the study group and 50 non-neoplastic patients in the control group. Blood samples were collected at baseline, after the first two cycles of chemotherapy and at progression in the study group and at entry in the control group. Serum VEGF-A was measured by chemiluminescence, SII was calculated based on complete blood count results, and the relationship between the VEGF-A/SII and clinicopathological characteristics, chemotherapeutic efficacy and progression-free survival (PFS) of SCLC patients was analyzed. Results: Baseline serum VEGF-A was significantly higher in SCLC patients than in non-neoplastic patients (P<0.001), while baseline SII was not (P=0.114). There was no correlation between baseline VEGF-A and SII in SCLC patients (P=0.123); however, there was a significant correlation between baseline VEGF-A and disease stage and central nervous system (CNS) metastasis (P=0.021 and P=0.012, respectively), as well as between baseline SII and disease stage and liver metastasis (P=0.026 and P=0.018, respectively). Serum VEGF-A was significantly lower than the pretreatment level after 2 cycles of treatment (P=0.049) but was not different at progression (P=0.247). Baseline VEGF-A was correlated with the treatment response of first-line chemotherapy (P=0.001), while baseline SII was not (P=0.392). Kaplan-Meier survival analysis suggested that the PFS of first-line chemotherapy was significantly longer in the low-VEGF-A group at baseline than the high-VEGF-A group (11.37 vs. 6.17 months, P<0.001). There was a trend toward longer PFS of first-line chemotherapy in the low-SII group at baseline than the high-SII group, but the difference was not significant (12.10 vs. 9.10 months, P>0.050). Univariate and multivariate Cox regression analyses suggested that baseline VEGF-A (HR: 3.443, 95% CI: 1.330-8.908, P=0.011) was an independent prognostic factor for PFS in SCLC patients. Conclusions: Baseline serum VEGF-A and SII are associated with important clinicopathological characteristics of SCLC patients. VEGF-A, but not SII, has the ability of diagnosis and predicting first-line chemotherapeutic efficacy and prognosis in SCLC patients.

A Comparative Study of Seminars Combined with Case-Based Learning versus Lecture-Based Learning for Cancer Pain Teaching in Medical Oncology Internship.

PURPOSE: To determine whether the teaching method of seminars combined with case-based learning (CBL) is superior to the traditional lecture-based learning (LBL) for teaching cancer pain in medical oncology internship. METHODS: Sixty medical and nursing interns in the medical oncology department of our hospital were selected between January 2019 and December 2020. Thirty students received traditional LBL instruction as the control group, and 30 students received combined seminars and CBL instruction as the observation group. The teaching evaluation and assessment was performed by theoretical and practical examinations and questionnaires. RESULTS: In the after-class examination, case analysis, clinical practice and overall scores of the observation group were higher than those of the control group (all p < 0.001). Theoretical knowledge scores did not differ significantly between the two groups (p = 0.470). In the questionnaire regarding attitudes towards opioid use, the observation group had better perceptions of using opioids than the control group (all p < 0.01). In the meantime, students in the observation group outperformed the control group in four aspects: self-learning (p < 0.001), analytical and problem-solving (p < 0.001), clinical thinking (p = 0.001), and clinical practice (p = 0.002) abilities all improved, while stimulating learning interest (p = 0.184) and enhancing theoretical knowledge mastery (p = 0.221) were not significantly different from those of the control group. Overall, students in the observation group were more satisfied with the teaching, teaching methods and teacher performances than the control group (all p < 0.001). CONCLUSION: Compared to the LBL, the combination of seminars and CBL is a more effective teaching method for cancer pain management, which is worth further study.

Clinical and molecular characteristics of secondary breast metastases from primary lung cancer: a study of 22 Chinese cases.

BACKGROUND: To analyze the clinical and molecular characteristics, as well as pathologic diagnosis and treatment of lung tumors that spread to the breast in 22 Chinese patients. MATERIALS AND METHODS: A systematic literature search of PubMed, Embase, ScienceDirect, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database and Wanfang Databases was conducted to identify the related studies published before March 31, 2020. A case of a 64-year-old man who underwent pneumonectomy and who was eventually diagnosed with a breast lump 5 years after surgery at our hospital, was also included in the present study. We analyzed the clinical and immunohistochemical characteristics from these case reports. RESULTS: The analysis totally incorporates 21 case reports and our own case, covering 22 subjects. Among all cases we found 11 adenocarcinomas, 7 small-cell carcinomas, and 4 squamous carcinomas. In addition, most of metastatic breast masses were located below or near the nipple, rather than in the outer quadrant. The results of immunohistochemistry mostly showed triple negative breast cancers. CONCLUSION: A lung cancer patient with a breast tumor should suggest the possibility of metastasis. It is extremely difficult to distinguish secondary breast cancer from primary simply through medical observation and pathologic testing. Additional immunohistochemical examinations are necessary to avoid delays in diagnosis and treatment.

Molecular phenotype discordance between primary and synchronous metastatic lesions of breast cancer and its determinant role in guiding treatment decisions: a case report.

Molecular phenotype discordance between primary and metastatic tumors exists in a small proportion of breast cancer (BC) patients with accessible synchronous metastases. Reduced therapeutic effect and delays in treatment can occur when decisions on systemic therapy are determined by ignoring the differences in tumor type. Here we report a 54-year-old post-menopausal locally advanced BC patient, who showed no tumor response following routine treatment which included targeting anti-HER2, based on the phenotype of primary tumor (Luminal B, HER2-positive), during neoadjuvant therapy. However, following a secondary biopsy of the metastatic subclavian lymph node, a distinct pathological feature (Triple-negative) was revealed; chemotherapy was adjusted accordingly and resulted in a positive tumor response. Various subclones within primary and metastatic lesions were identified which might be attributed to tumor heterogeneity and in turn resulting in the phenotypic discordance in the receptor status. The patient died due to tumor progression related to triple-negative-featured lung metastasis, with overall survival time of 26.4 months. This study strengthens the value of concurrent biopsies of both primary and synchronous metastatic lesions in BC patients, and provides a reference for treating this kind of tumor when discordance in the molecular phenotype is observed.

Metastatic brain tumors respond favorably to pyrotinib in a HER2-positive breast cancer following failure using trastuzumab.

Treatment of breast cancer (BC) with overexpression of human epidermal growth factor receptor 2 (HER2) has undergone a prosperous development with the advent of emerging small molecule tyrosine kinase inhibitors (TKIs). However, their efficacy in brain metastases (BMs) requires further investigation in both clinical trials and practice by specifically targeting this population. We herein reported a HER2-positive metastatic bilateral BC case with symptomatic diffusion of parenchymal BM after first-line treatment with trastuzumab-based regimen. She then received pyrotinib (with a disease-free survival of 5.7 months) followed by whole brain radiotherapy. Unexpectedly, under satisfactory control of intracranial parenchymal lesions, the patient based on clinical manifestations, auxiliary examinations and exclusive diagnosis was diagnosed with meningeal progression, and soon died of tumor progression. Thus, pyrotinib response differed from meningeal to parenchymal BM in BC patients, and the need of comprehensive and systematic evaluation of TKIs in some particular clinical scenarios has become a critical issue.

High STRN Expression Promotes HCC Invasion and Migration but Not Cell Proliferation or Apoptosis through Facilitating Epithelial-Mesenchymal Transition.

A STRN-ALK fusion protein has been recently identified as a potential therapeutic target in multiple cancers; however, the role of STRN alone in regulating the biological function of hepatocellular carcinoma (HCC) remains unclear. In this study, we firstly detected an overexpression of STRN in HCC tissues compared to that in adjacent nontumour (ANT) tissues through IHC analysis, and the expression level of this protein was positively correlated with lymph node metastasis and TNM stage. In vitro, high expression of STRN was also confirmed in different HCC cell lines, and regulation of STRN expression in Huh7 cells did not significantly affect tumour cell proliferation or apoptosis but was positively correlated with tumour cell invasion and migration capacities. Moreover, both the knockdown and overexpression of STRN in Huh7 cells can lead to cell morphological changes that are accompanied with an alteration of epithelial-mesenchymal transition (EMT) molecular markers E-cadherin and Vimentin. Finally, STRN was further proved to be negatively related to E-cadherin expression but positively related to Vimentin expression in human HCC tissue samples. Taken together, STRN is upregulated in HCC and acts as a tumour promoter regulating cell invasion and migration through facilitating the EMT process.

Complete response to crizotinib in a metastatic adenocarcinoma of unknown primary harboring MET amplification and NTRK1 co-occurring mutation.

Carcinomas of unknown primary (CUPs) have poor prognosis due to the paucity of data on their clinical characteristics and laboratory features, and empirical chemotherapy still remains the critical management for this kind of disease. This study aimed to present the knowledge of treating an elderly man with metastatic adenocarcinoma of unknown primary and also with a history of long-term hypertension and renal cysts. He was identified to harbor mesenchymal-epithelial transition factor (MET) gene amplification and neurotrophic tyrosine receptor kinase 1 (NTRK1) gene co-occurring mutation by targeted next-generation sequencing analysis upon the progression of empirical chemotherapy. He was then treated with a standard dose of crizotinib (250 mg, twice daily), which exhibited a satisfactory complete response (CR) of the targeted lesions after 1 month of treatment. When the number of renal cysts increased and renal inadequacy occurred after treatment for 2 months, crizotinib was reduced to half-dose (250 mg, once daily), and still conferred maintenance of CR for another 6.5 months and good quality life of the patient. These results suggested that treatments based on driver genes rather than primary tumor types could be a promising manipulation for achieving better treatment outcome, and a half-dose of crizotinib might be both effective and tolerable for MET-overexpressed CUPs with underlying renal diseases.

Connexin 32 downregulation is critical for chemoresistance in oxaliplatin-resistant HCC cells associated with EMT.

Background: Oxaliplatin (OXA)-based chemotherapy is critical in the management of advanced hepatocellular carcinoma (HCC); however, acquired drug resistance has largely restricted its clinical efficacy. This study aims to explore the key mechanisms and regulatory factors determining chemosensitivity in HCC. Methods: We developed OXA-resistant (OR) HCC cells and used multiple methods, including real-time RT-PCR, Western blot, immunofluorescence, transwell invasion assay, wound-healing assay, MTT assay, gene transfection, and immunohistochemistry to achieve our goals. Results: We found that OR HCC cells showed a typical epithelial-mesenchymal transition (EMT) phenotype. Meanwhile, the expression of Cx32, a major member of the liver connexin (Cx) family, was lowly expressed in OR HCC cells. Downregulation of Cx32 in parental HCC cells led to EMT induction and thereby reduced OXA cytotoxicity, while Cx32 upregulation in OR HCC cells could reverse the EMT phenotype and partially restore chemosensitivity to OXA. Finally, in human HCC tissue samples, Cx32 was positively correlated with the expression of the EMT marker E-cadherin and negatively correlated with the expression of Vimentin. Conclusion: Our findings demonstrated that downregulation of Cx32 may be an important determinant for HCC cells to acquire EMT-related acquired drug resistance to OXA, and targeting Cx32 could be a novel strategy to overcome OXA resistance in HCC.