IntroductionNasopharyngeal carcinoma (NPC) is a common malignancy in China and known prognostic factors are limited. In this study, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) were evaluated as prognostic factors in locally advanced NPC patients.Materials and MethodsNPC patients who received curative radiation or chemoradiation between January 2012 and December 2015 at the Second Xiangya Hospital were retrospectively reviewed, and a total of 516 patients were shortlisted. After propensity score matching (PSM), 417 patients were eventually enrolled. Laboratory and clinical data were collected from the patients’ records. Receiver operating characteristic curve analysis was used to determine the optimal cut-off value. Survival curves were analyzed using the Kaplan-Meier method. The Cox proportional hazard model was used to identify prognostic variables.ResultsAfter PSM, all basic characteristics between patients in the high SIRI group and low SIRI group were balanced except for sex (p=0.001) and clinical stage (p=0.036). Univariate analysis showed that NLR (p=0.001), PLR (p=0.008), SII (p=0.001), and SIRI (p<0.001) were prognostic factors for progression-free survival (PFS) and overall survival (OS). However, further multivariate Cox regression analysis showed that only SIRI was an independent predictor of PFS and OS (hazard ratio (HR):2.83; 95% confidence interval (CI): 1.561-5.131; p=0.001, HR: 5.19; 95% CI: 2.588-10.406; p<0.001), respectively.ConclusionOur findings indicate that SIRI might be a promising predictive indicator of locally advanced NPC patients.

Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. Copper transporter protein 1 (CTR1), a copper influx transporter required for high affinity copper (probably reduced Cu I) transport into the cell, reportedly promotes a significant fraction of DDP internalization in tumor cells. In the present study, we evaluated the function of CTR1 in the cell proliferation of cervical cancer upon DDP treatment. MicroRNAs (miRNAs) have been regarded as essential regulators of cell proliferation, apoptosis, migration, as well as chemoresistance. By using online tools, we screened for candidate miRNAs potentially regulate CTR1, among which miR-130a has been proved to promote cervical cancer cell proliferation through targeting PTEN in our previous study. In the present study, we investigated the role of miR-130a in cervical cancer chemoresistance to DDP, and confirmed the binding of miR-130a to CTR1. SOX9 also reportedly act on cancer chemoresistance. In the present study, we revealed that SOX9 inversely regulated miR-130a through direct targeting the promoter of miR-130a. Consistent with previous studies, SOX9 could affect cervical cancer chemoresistance to DDP. Taken together, we demonstrated a SOX9/miR-130a/CTR1 axis which modulated the chemoresistance of cervical cancer cell to DDP, and provided promising targets for dealing with the chemoresistance of cervical cancer.

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EGFR-TKIs have been widely used in the first-line treatment of NSCLC patients harboring EGFR mutations. However, the prognosis indicators are limited. In the present study, the prognostic value of systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) were assessed in EGFR-Mutant lung adenocarcinoma patients treated with first-generation EGFR-TKIs. Two hundred three patients were included in this retrospective analysis. SII was calculated as platelet counts × neutrophil counts / lymphocyte counts. Receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off value for SII, NLR, and PLR. Univariate and multivariate survival analysis were performed to identify factors correlated with PFS and OS. Applying cut-offs of ≥1066.935 (SII), ≥4.40 (NLR), and ≥182.595 (PLR), higher NLR was associated with worse Eastern Cooperative Oncology Group performance status (ECOG PS) (P = .006), and higher brain metastasis rate (P = .03), higher PLR was associated with smoking history (P = .037), and worse ECOG PS (P = .001), and higher SII groups were associated with worse ECOG PS (P = .002). In univariate analysis, higher NLR (P < .001), higher PLR (P = .002), and higher SII (P < .001) were associated with worse PFS. Higher NLR (P < .001), and higher SII (P < .001) were associated with worse OS. In multivariate analysis, NLR (HR 1.736;95%CI:1.020–2.954; P = .03), PLR (HR 1.823; 95%CI:1.059–3.137; P = .04), and SII (HR2.577; 95%CI:1.677–3.958; P < .001) were independently correlated with PFS. While only SII (HR 2.802; 95%CI:1.659–4.733; P < .001) was independently correlated with OS. The present study demonstrated that SII is an independent prognostic factor for poor survival of advanced EGFR-Mutant lung adenocarcinoma patients treated with first-generation TKIs.

Abstract. Pulmonary sarcomatoid carcinoma (PSC) is a rare histological subtype of non-small cell lung cancer, and the available studies on the response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is limited. In the present study, a 73-year-old female presented with a large mass in the lower right lung, which was diagnosed as a PSC on biopsy. An amplification-refractory mutation system (ARMS) test revealed that the patient possessed the wild-type EGFR gene, and the patient subsequently underwent radiotherapy (60 Gy) and four 21-day cycles of chemoradiotherapy (1,600 mg gemcitabine, days 1 and 8; 30 mg, cisplatin, days 1-3). Following radiotherapy and chemotherapy treatment, a CT scan revealed complete remission of the mass in the lower right lung, however, metastases were identified in the paraaortic lymph node, bilateral iliac fossa and the right gluteal region. Notably, an EGFR exon 21 L858R gene mutation was identified in the mass of the right gluteal metastasis. Therefore, treatment with erlotinib was initiated. The patient continued to experience progression-free survival for six months following the initiation of erlotinib therapy. However, multiple metastases were then identified, and all lesions possessed the wild-type EGFR gene, as identified by the ARMS test. The findings suggest that erlotinib is a viable therapeutic option for the treatment of PSC patients that possess an EGFR mutation. The spatio-temporal evolution of EGFR mutational heterogeneity in PSC may result in drug-resistance, which challenges EGFR-TKI therapy and EGFR gene mutation diagnosis.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma worldwide. Although patient outcomes have significantly improved to a greater than 40% cure rate by the combinatorial cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, which is widely used, resistance to the CHOP regimen continues to pose a problem in managing or curing DLBCL. While it promotes the malignancy and chemo-resistance in certain types of cancer, Annexin A5 is negatively correlated with those in other cancers, including DLBCL. In the present study, we explored the effects of Annexin A5 on DLBCL cell invasion and chemoresistance to CHOP. Stable overexpression and knockdown of Annexin A5 were performed in Toledo and Pfeiffer human DLBCL cell lines. Overexpression of Annexin A5 in both cell lines significantly decreased cell invasion, matrix metalloproteinase-9 (MMP-9) expression/activity, phosphatidylinositol 3-kinase (PI3K) activity/Akt phosphorylation, and cell survival against CHOP-induced apoptosis. On the other hand, knockdown of Annexin A5 markedly increased cell invasion, MMP-9 expression/activity, PI3K activity/Akt phosphorylation, and CHOP-induced apoptosis in the DLBCL cell lines, which was abolished by selective PI3K inhibitor BKM120. In conclusion, our study provides the first in vitro evidence that Annexin A5 inhibits DLBCL cell invasion, MMP-9 expression/activity, and chemoresistance to CHOP through a PI3K-dependent mechanism; it provides new insight not only into the biological function of Annexin A5, but also into the molecular mechanisms underlying DLBCL progression and chemoresistance.

Pembrolizumab, an immune checkpoint inhibitor against the programmed death-1 pathway, has been used in combination with acitinib for the first-line treatment of advanced renal cell carcinoma. Neurotoxicity is a rare immune-related adverse event (irAE). The present study reports a case of Guillain-Barre syndrome (GBS) induced by pembrolizumab and sunitinib, and reviews other previous studies to elucidate the clinical characteristics and suitable management of this rare irAE. An advanced renal cell carcinoma patient who received several cycles of pembrolizumab combined with sunitinib developed limb weakness and numbness of the extremities, and was diagnosed with GBS by electrodiagnostic and cerebrospinal fluid examination. The patient improved after treatment with intravenous immunoglobulin along with prednisone. To the best of our knowledge, this is the first case of GBS during treatment with pembrolizumab in combination with sunitinib in advanced renal cell carcinoma.