Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

Addition of temozolamide as radiosensitizer in brain metastasis: experience from a resource limited centre in sub-Himalayan region

Background: Brain metastasis is a common, debilitating and undesirable neurological complication of systemic cancer and a significant cause of morbidity and mortality. Methods: 39 patients of brain metastasis with Ca breast/Ca lung as primaries were randomized into a study arm and control arm in between 1st August 2018 to 31st July 2019 at IGMC Shimla. Control arm consisted of WBRT (30 GY/10 fractions/5 days a week). Study arm consisted of WBRT with same dose and temozolamide administered 75mg /m2/day during RT days. Results: Out of 39 patients 34 patients completed treatment out of which 17 in study and 17 in control arm. Response to brain lesions could not be assessed in 20 out of 39 patients. In remaining 19 patients 36.8% patients in study arm and 20% patients in control arm had partial response (PR). 5.3% patient in study arm and none in control arm has complete response (CR). 25% patients in control arm and 15.8% patients in study arm had stable disease. Improvement in QOL (FACT- G) seen in both study and control arm post Rx, however improvement sustained in study arm at 1st F/u. Conclusions: Leveraging the additional radio-sensitizing effect of TMZ may hold promise as an attractive strategy to enhance the quality of life in patients with a favourable performance status. Moreover, RPA could serve as a decisive factor in tailoring the treatment approach, guiding the choice between palliative radiotherapy and best supportive care for these individuals.

Comparison of two palliative regimens of radiation on the quality of life in metastatic non small cell lung cancer

Background: Lung cancer is one of the most common cancers in males worldwide and its number is increasing every year. Of these cases 75-80% case are of non-small cell type. Methods: This study was conducted on 30 patients of stage IV non-small cell lung cancer in the department of radiation oncology at tertiary care center, Shimla, Himachal Pradesh India from 1st Jun 2019 to 30th Jun 2020 by dividing them into study and control arm for assessing quality of life (QOL) with EORTC QLQ-C30 version3.0. Results: We observed significant improvement in Global health scale of control arm (p=0.005) but it got worse in study arm (p=0.743). All the parameters of Functional scale i.e. Physical (p=0.584; 0.170), Role (p=0.213; 0.016), Emotional (p=0.239; 0.002), Cognitive (p=0.793; 0.247) and Social functioning (p=0.030; 0.231) got worse in study arm while they improved in control arm. As far as Symptom scale is concerned, in the study arm; dyspnea (p=0.724), appetite (p=0.836), constipation (0.192), diarrhea (p=0.341) improved but other symptoms like fatigue (p=0.566), nausea (p=0.347), pain (p=0.305), insomnia (p=0.025), financial difficulties (p=0.082) got worse while in control arm; fatigue (p=0.003), pain (p=0.000), dyspnea (p=0.022), insomnia (p=0.336), appetite (p=0.028), constipation (0.019), diarrhea (p=0.336), financial difficulties (p=0.336) improved and nausea (p=0.120) got worse. Conclusion: QOL assessment by the physician before commencement of the treatment and later on at every visit seems to be beneficial for symptom relief and to allay the anxiety of both patient and their attendants.

Cytotoxic Effects of Xanthohumol and Its Combination with Cisplatin on Human Metastatic Lung Cancer H1299 Cells

Aims:Non-small cell lung cancer (NSCLC) accounts for high lung cancer death that is mostly associated with advanced disease stage at diagnosis and resistance to chemotherapy. In the present study, we investigated whether xanthohumol, a prenylated flavonoid of hop plant, induces metastatic lung cancer H1299 cell death, and whether in combination with cisplatin there are additive effects. Methodology:H1299 cells were grown and treated with xanthohumol (6.25, 12.5, or 25 μM), cisplatin (12.5, 25, or 50 μM) and the combination of cisplatin and xanthohumol for 24 h. Cell viability, cell morphology, chromatin condensation, ɣH2AX, cPARP-1, capsase-3, p21WAF1/CIP1and p14ARFgenes were analyzed Results:Xanthohumol, cisplatin, and the combination of cisplatin and xanthohumol inhibited H1299 cells viability. Cisplatin growth inhibitory effects were potentiated by xanthohumol. Xanthohumol induced chromatin condensation and apoptosis and potentiated cisplatin’s effect vs cisplatin alone. Further investigation of growth inhibitory effects, xanthohumol alone induced γH2AX foci formation and the combination potentiated γH2AX foci formation. Cisplatin, xanthohumol at 25 μM, and the combination of cisplatin and xanthohumol at 6.25 and 12.5 μM increased cPARP-1 level. Active caspase-3 was increased by cisplatin, 12.5 μM of xanthohumol, and the combination of xanthohumol and cisplatin. Xanthohumol at 6.25 or 12.5 μM potentiated cisplatin effect on active caspase-3 and cPARP-1, respectively. Xanthohumol at 25 μM significtly induced the expression cell cycle control genes p21WAF1/CIP1and p14ARF. These results indicate that xanthohumol inhibits proliferation of H1299 cells and induces cell death through cleavage of PARP-1 and activation of caspase-3. The combination of cisplatin and xanthohumol potentiated cytotoxic effects of each other compound.Conclusion:The present study suggests that xanthohumol poses apoptotic effects and potentiates cisplatin’s growth inhibitory effects on metastatic lung cancer cells