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Hyperplasia suppressor gene (HSG), also called human mitofusin 2, is a novel gene that markedly suppresses the cell proliferation of hyperproliferative vascular smooth muscle cells from spontaneously hypertensive rat arteries. This gene encodes a mitochondrial membrane protein that participates in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. In this report, we showed that an adenovirus vector encoding human HSG (Ad5-hHSG) had an antitumor activity in a wide range of cancer cell lines. We further focused on the lung cancer cell line A549 and the colon cancer cell line HT-29 and then observed that Ad5-hHSG induced apoptosis both in vitro and in vivo. Confocal laser scanning microscopy and electron microscopy revealed that cells infected with Ad5-hHSG formed dose-dependent perinuclear clusters of fused mitochondria. Adenovirus-mediated hHSG overexpression induced apoptosis, cell cycle arrest, mitochondrial membrane potential (#8m) reduction and release of cytochrome c, caspase-3 activation, and cleavage of PARP in vitro. Overexpression of hHSG also significantly suppressed the growth of subcutaneous tumors in nude mice both ex vivo and in vivo. In addition, Ad5-hHSG increased the sensitivity of these cell lines to two chemotherapeutic agents, VP16 and CHX, and radiation. These results suggest that Ad5-hHSG may serve as an effective therapeutic drug against tumors.

• MR imaging has served as a problem-solving procedure in ectopic pregnancy. • MR imaging features can be criteria for early diagnosis of tubal pregnancy. • Detailed assessment of ectopic implantation is necessary for management decision-making.

A methodology for calibration-free wavelength modulation spectroscopy (CF-WMS) that is based upon an extensive empirical description of the wavelength-modulation frequency response (WMFR) of DFB laser is presented. An assessment of the WMFR of a DFB laser by the use of an etalon confirms that it consists of two parts: a 1st harmonic component with an amplitude that is linear with the sweep and a nonlinear 2nd harmonic component with a constant amplitude. Simulations show that, among the various factors that affect the line shape of a background-subtracted peak-normalized 2f signal, such as concentration, phase shifts between intensity modulation and frequency modulation, and WMFR, only the last factor has a decisive impact. Based on this and to avoid the impractical use of an etalon, a novel method to pre-determine the parameters of the WMFR by fitting to a background-subtracted peak-normalized 2f signal has been developed. The accuracy of the new scheme to determine the WMFR is demonstrated and compared with that of conventional methods in CF-WMS by detection of trace acetylene. The results show that the new method provides a four times smaller fitting error than the conventional methods and retrieves concentration more accurately.

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Abstract. Cisplatin (cis-diamminedichloroplatinum II, CDDP) acts as a therapeutic agent by initiating cellular apoptosis. However, side-effects and drug resistance limit the clinical use of cisplatin. Numerous studies have focused on the drug-target interactions, cellular pharmacology and pharmacokinetics of cisplatin. Newly developed treatment strategies are needed in order to be used in combination with cisplatin, with the aim to minimize toxicity and to circumvent cisplatin resistance. Ammonium chloride (NH 4 Cl) is widely used in various areas, but its use as a combination agent with cisplatin for the treatment of cancer cells has not been previously reported. In the present study, we showed that NH 4 Cl could be potentially used as an effective agent in cisplatin combination treatment of HeLa human cervical cancer (HCC) cells. Cisplatin was found to inhibit cell growth, as well as to induce cell apoptosis and DNA double-strand breaks. In addition, treatment with NH 4 Cl increased the rate of cell apoptosis and the activation of caspase-3. Particularly, we found that NH 4 Cl treatment increased cisplatin-induced phosphorylation of H 2 AX. In conclusion, our data indicate that NH 4 Cl enhances cisplatin cytotoxicity through increased DNA damage in HeLa HCC cells. IntroductionCisplatin (cis-diamminedichloroplatinum II, CDDP) is one of the most effective chemotherapeutic agents widely used for the treatment of solid tumors. However, the side-effects of cisplatin chemotherapy and resistance during the course of the treatment limit its clinical use (1-3). Cisplatin is generally considered as a cytotoxic drug which kills cancer cells by damaging DNA and inhibiting DNA synthesis. Cisplatin-induced DNA damage activates various signaling pathways to prevent or promote cell death predominantly by inducing apoptosis (4). Based on the mechanism of action of cisplatin-induced cell death, modifications to the combination methods used in chemotherapy are required to reduce the side-effects and increase the therapeutic effects of cisplatin. Autophagy inhibitors, such as 3-methyladenine and chloroquine, have been shown to effectively enhance cisplatin cytotoxity (5-8). Additional agents have been recently assessed such as bortezomib (PS-341, Velcade), a proteasome inhibitor (9,10), and histone acetyltransferase inhibitor, suberoylanilide hydroxamic acid (SAHA) (11,12). Some of these agents have been shown to confer sensitizing effects to cisplatin combination therapy.Ammonium chloride (NH 4 Cl) is an agent used for the treatment of metabolic alkalosis in clinical practice (13). NH 4 Cl was recently used as an autophagy inhibitor in in vitro studies, where it was found to affect the pH of lysosomes and to disturb the activity of autolysosomes (14-16). In the present study, we used NH 4 Cl combined with cisplatin to investigate the potentially effective use of NH 4 Cl as an agent in cisplatin combination chemotherapy.In the present study, we tested the hypothesis that the use of NH 4 Cl increases the apoptosis induced by cispl...

The eighth TNM staging system proposal classifies lung cancer with partial or complete atelectasis/obstructive pneumonia into the T2 category. We aimed to develop nomograms to predict the possibility of lymph node metastasis (LNM) and the prognosis for NSCLC based on atelectasis and obstructive pneumonitis. Methods: NSCLC patients over 20 years old diagnosed between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The nomograms were based on risk factors that were identified by Logistic regression. The area under the receiver operating characteristic (ROC) curve (AUC) was performed to confirm the predictive values of our nomograms. Cox proportional hazards analysis and Kaplan–Meier survival analysis were also used in this study. Results: A total of 470,283 patients were enrolled. Atelectasis/obstructive pneumonitis, age, gender, race, histologic types, grade, and tumor size were defined as independent predictive factors; then, these seven factors were integrated to establish nomograms of LNM. The AUC is 0.70 (95% CI: 0.694–0.704). Moreover, the Cox proportional hazards analysis and Kaplan–Meier survival analysis showed that the scores derived from the nomograms were significantly correlated with the survival of pathological N0 classification. Conclusion: Nomograms based on atelectasis/obstructive pneumonitis were developed and validated to predict LNM and the postoperative prognosis of NSCLC.

This study constructed and validated a prognostic model to evaluate the survival of small-cell lung cancer (SCLC) patients following surgery, and shed light on the strategy of postoperative radiotherapy. A total of 882 patients from Shanghai Pulmonary Hospital and the Surveillance, Epidemiology and End Results database after lung resection were selected. Multivariable Cox analysis was used to identify the indicators affecting long-term survival in patients. A nomogram was constructed to predict the prognosis of eligible patients. Indices of concordance (C-index) was used to access the predictive ability of cancer-specific survival (CSS) for the prognostic model. CSS discrimination in the prognostic model was comparable in the training and validation cohorts (C-index = 0.637[NORAD-T], 0.660[NORAD-V], 0.656[RAD] and 0.627[our hospital], respectively. Stratification based on the cutoff value of the nomogram yielded low- and high-risk subgroups in four cohorts. For patients in the high-risk group, postoperative radiotherapy was considered a survival-promoting strategy (unadjusted HR 0.641, 95% CI 0.469–0.876, p = 0.0046). In the low-risk group, however, the implementation of radiotherapy barely had an influence on CSS. In conclusion, the nomogram we constructed and validated could predict the prognosis of SCLC patients followed surgery and identify high-risk patients who were likely to benefit from postoperative radiotherapy.