Immunochemotherapy achieved a complete response for metastatic adenocarcinoma of unknown primary based on gene expression profiling: a case report and review of the literature

BackgroundCancer of unknown primary (CUP) is a malignant and aggressive tumor whose primary origin is still unknown despite thorough evaluation. CUP can be life-threatening with a median overall survival of less than 1 year based on empirical chemotherapy. Gene detection technology advances the driver gene detection of malignant tumors and the appropriate precise therapy. Immunotherapy has ushered in a new era in cancer therapy, changing the way advanced tumors, including CUP, are treated. Combined with comprehensive clinical and pathological investigations, molecular analysis of the original tissue and detection of potential driver mutations may provide therapeutic recommendations for CUP.Case presentationA 52-year-old female was admitted to hospital for dull abdominal pain, with peripancreatic lesions below the caudate lobe of the liver and posterior peritoneal lymph nodes enlargement. Conventional biopsy under endoscopic ultrasonography and laparoscopic biopsy both revealed poorly differentiated adenocarcinoma based on immunohistochemical series. To help identify tumor origin and molecular characteristics, 90-gene expression assay, tumor gene expression profiling with Next-generation sequencing (NGS) method and Immunohistochemical expression of PD-L1 were employed. Although no gastroesophageal lesions discovered by gastroenteroscopy, the 90-gene expression assay yielded a similarity score and prompted the most likely primary site was gastric/esophagus cancer. NGS revealed high TMB (19.3mutations/Mb) but no druggable driver genes identified. The Dako PD-L1 22C3 assay IHC assay for PD-L1 expression revealed a tumor proportion score (TPS) of 35%. Given the presence of negative predictive biomarkers for immunotherapy, including adenomatous polyposis coli (APC) c.646C>T mutation at exon 7 and Janus kinase 1(JAK1), the patient received immunochemotherapy instead of immunotherapy alone. She was successfully treated with nivolumab plus carboplatin and albumin-bound nanoparticle paclitaxel for six cycles and nivolumab maintenance, which achieved a complete response (CR) maintained for 2 years without severe adverse events.ConclusionsThis case highlights the value of multidisciplinary diagnosis and individual precision treatment in CUP. Further investigation is needed as an individualized treatment approach combining immunotherapy and chemotherapy based on tumor molecular characteristics and immunotherapy predictors is expected to improve the outcome of CUP therapy

Interaction of autophagy with microRNAs and their potential therapeutic implications in human cancers

AbstractAutophagy is a tightly regulated intracellular self-digestive process involving the lysosomal degradation of cytoplasmic organelles and proteins. A number of studies have shown that autophagy is dysregulated in cancer initiation and progression, or cancer cells under various stress conditions. As a catabolic pathway conserved among eukaryotes, autophagy is regulated by the autophagy related genes and pathways. MicroRNAs (miRNAs) are small, non-coding endogenous RNAs that may regulate almost every cellular process including autophagy. And autophagy is also involved in the regulation of miRNAs expression and homeostasis. Here we reviewed some literatures on the interaction of miRNAs with autophagy and the application of miRNAs-mediated autophagic networks as a promising target in pre-clinical cancer models. Furthermore, strategies of miRNAs delivery for miRNAs-based anti-cancer therapy will also be summarized and discussed

Photon-assistant Fano resonance in coupled multiple quantum dots

Based on calculations of the electronic structure of coupled multiple quantum dots, we study systemically the transport properties of the system driven by an ac electric field. We find qualitative difference between transport properties of double coupled quantum dots (DQDs) and triple quantum dots. For both symmetrical and asymmetrical configurations of coupled DQDs, the field can induce the photon-assisted Fano resonances in current-AC frequency curve in parallel DQDs, and a symmetric resonance in serial DQDs. For serially coupled triple quantum dots(STQDs), it is found that the $\Lambda$-type energy level has remarkable impact on the transport properties. For an asymmetric (between left and right dots) configuration, there is a symmetric peak due to resonant photon induced mixing between left/right dot and middle dot. In the symmetric configuration, a Fano asymmetric line shape appears with the help of ``trapping dark state". Here the interesting coherent trapping phenomena, which usual appear in quantum optics, play an essential role in quantum electronic transport. We provide a clear physics picture for the Fano resonance and convenient ways to tune the Fano effects.Comment: 7 pages, 5 figure

Waveform-Domain Adaptive Matched Filtering: A Novel Approach to Suppressing Interrupted-Sampling Repeater Jamming

The inadequate adaptability to flexible interference scenarios remains an unresolved challenge in the majority of techniques utilized for mitigating interrupted-sampling repeater jamming (ISRJ). Matched filtering system based methods is desirable to incorporate anti-ISRJ measures based on prior ISRJ modeling, either preceding or succeeding the matched filtering. Due to the partial matching nature of ISRJ, its characteristics are revealed during the process of matched filtering. Therefore, this paper introduces an extended domain called the waveform domain within the matched filtering process. On this domain, a novel matched filtering model, known as the waveform-domain adaptive matched filtering (WD-AMF), is established to tackle the problem of ISRJ suppression without relying on a pre-existing ISRJ model. The output of the WD-AMF encompasses an adaptive filtering term and a compensation term. The adaptive filtering term encompasses the adaptive integration outcomes in the waveform domain, which are determined by an adaptive weighted function. This function, akin to a collection of bandpass filters, decomposes the integrated function into multiple components, some of which contain interference while others do not. The compensation term adheres to an integrated guideline for discerning the presence of signal components or noise within the integrated function. The integration results are then concatenated to reconstruct a compensated matched filter signal output. Simulations are conducted to showcase the exceptional capability of the proposed method in suppressing ISRJ in diverse interference scenarios, even in the absence of a pre-existing ISRJ model

Gene expression profile indicates involvement of NO in Camellia sinensis pollen tube growth at low temperature

DEGs identified from the comparison between control (CsPT-CK) and 4 °C-treated (CsPT-LT) pollen tbues. All of the samples were replicated three times. CK and LT FPKM: fragments per kb per million reads for each unigene in the CK and LT libraries, respectively. The log2Ratio (LT/CK): ratio between the FPKM of LT and CK. The absolute values of log2Ratio > 1 and probability > 0.7 were used as threshold for assigning significance. Annotation of DEGs against NR, NT, Swiss-Prot protein, KEGG, COG and GO were all reported in the tables. “-”: no hit. (XLS 381 kb

Traditional Chinese Medicine Improves Activities of Daily Living in Parkinson's Disease

We evaluated the effects of a traditional Chinese medicine (TCM), named Zeng-xiao An-shen Zhi-chan 2 (ZAZ2), on patients with Parkinson's disease (PD). Among 115 patients with idiopathic PD enrolled (mean age, 64.7 ± 10.2 years old), 110 patients (M = 65, F = 45; mean age, 64.9 ± 10.7 years old) completed the study. Patients took either ZAZ2 (n = 59) or placebo granule (n = 56) in a blind manner for 13 weeks while maintaining other anti-Parkinson medications unchanged. All participants wore a motion logger, and we analyzed the power-law temporal autocorrelation of the motion logger records taken on 3 occasions (before, one week, and 13 weeks after the drug administration). Drug efficacy was evaluated with the conventional Unified Parkinson Disease Rating Scale (UPDRS), as well as the power-law exponent α, which corresponds to the level of physical activity of the patients. ZAZ2 but not placebo granule improved the awake-sleep rhythm, the UPDRS Part II, Part II + III, and Part IV scores, and the α values. The results indicate that ZAZ2 improved activities of daily living (ADL) of parkinsonism and, thus, is a potentially suitable drug for long-term use

Quantitative Evaluation of Chinese Herb Medicine in the Treatment of Sialorrhea and Frequent Nighttime Urination in Patients with Parkinson’s Disease

Aims. To evaluate the efficacy of Lian-Se formula (LSF), one Chinese herb formulation for treating sialorrhea and frequent overnight urination in patients with Parkinson’s disease (PD). Methods. 96 PD patients suffering from sialorrhea and/or frequent nighttime urination were divided into two groups: an LSF group (n = 48) treated with LSF for 6 weeks and a placebo group (n = 48) treated with a placebo formula whose appearance and taste were the same as LSF for 6 weeks. All patients were treated by standard antiparkinsonism medicine according to the PD guideline of China. The changes of the quantity of saliva (QS) (mL), frequency of nighttime urination (FNU) and early sleep activity (ESA), and nocturnal activity (NA) by analyzing actigraphic records as the primary results and the total score of unified Parkinson’s disease rating scale (UPDRS) and the Epworth Sleepiness Scale (ESS) as the secondary results were used to evaluate the clinical efficacy in both groups. Results. There were no significant differences in the baseline values of QS, FNU, NA, ESA, UPDRS total score, and ESS between the two groups. At the end of week 6, the QS, FNU, NA, and ESA in the LSF group showed superior results to those of the placebo group with no differences in the total UPDRS score between the two groups during the investigation. The ESS was significantly improved at the end of week 6 compared with the baseline and the placebo group. Laboratory test results indicated there were no side effects in either group. Conclusion. The findings of LSF treatment have clear clinical effects in patients with sialorrhea and frequent overnight urination. LSF thus appears to be a potential choice as an additional drug that can improve the sialorrhea and frequent overnight urination symptoms of PD patients

Autophagy Inhibition Enhances Daunorubicin-Induced Apoptosis in K562 Cells

Anthracycline daunorubicin (DNR) is one of the major antitumor agents widely used in the treatment of myeloid leukemia. Unfortunately, the clinical efficacy of DNR was limited because of its cytotoxity at high dosage. As a novel cytoprotective mechanism for tumor cell to survive under unfavorable conditions, autophagy has been proposed to play a role in drug resistance of tumor cells. Whether DNR can activate to impair the sensitivity of cancer cells remains unknown. Here, we first report that DNR can induce a high level of autophagy, which was associated with the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Moreover, cell death induced by DNR was greatly enhanced after autophagy inhibition by the pharmacological inhibitor chloroquine (CQ) and siRNAs targeting Atg5 and Atg7, the most important components for the formation of autophagosome. In conclusion, we found that DNR can induce cytoprotective autophagy by activation of ERK in myeloid leukemia cells. Autophagy inhibition thus represents a promising approach to improve the efficacy of DNR in the treatment of patients with myeloid leukemia