Progress of Immunotherapy Combined with Anti-Angiogenesis Therapy in Lung Cancer

Lung cancer is the most prevalent and fatal cancer in China and even around the world, and many patients are found in the late stage of lung cancer. For the treatment of advanced lung cancer, in addition to traditional chemotherapy modalities, many emerging treatments are increasingly significant, such as immunotherapy, anti-angiogenic therapy, and targeted therapy. An increasing number of studies have now shown that anti-angiogenic therapy improves the immune microenvironment by enhancing tumor immunity through normalization of tumor vessels. Immunization combined with anti-angiogenic therapy can exert synergistic effects and improve the prognosis of patients. This article summarizes the extent of benefit, current clinical study data, and future prospects of immunotherapy combined with anti-angiogenic agents in the treatment of advanced NSCLC.

Research Progress of Anti-Angiogenic Drugs in First-Line Treatment of Small Cell Lung Cancer

Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effective treatment now. As an active research direction at present, anti-angiogenic drugs are not only widely used in non-small cell lung cancer and other tumors, but also have certain effects in small cell lung cancer combined with chemotherapy. As one of the effective treatment methods for small cell lung cancer, related research is not rare, but there is still inadequacy, such as side effects can not be tolerated, and the timing of treatment can not be accurately assessed. This article will briefly describe the research progress of anti-angiogenic drugs combined with chemotherapy in the first-line treatment of extensive small cell lung cancer.

Aminated Cyclopropylmethylphosphonates as Potent Prostate Cancer Inhibitors

Inspired by the anti-pancreatic promising results of our novel aminated cyclopropylmethylphosphonate compounds, an in vitro anti-prostate cancer activity exploration of these compounds was carried out on human prostate cancer cell line PC-3, and showed potent inhibiting activity at low micromolar concentrations (with an IC50 of approximately 45 μM).

Drug-Drug Interactions in Patients with Breast Cancer

The research paper investigates the intricate landscape of drug-drug interactions (DDIs) within the context of breast cancer treatment, with a particular focus on the elderly population and the use of complementary and alternative medicine (CAM). The study underscores the heightened susceptibility of elderly patients to DDIs due to the prevalence of polypharmacy and the widespread utilization of CAM among breast cancer patients. The potential ramifications of DDIs, encompassing adverse drug events and diminished treatment efficacy, are elucidated. The paper accentuates the imperative for healthcare providers to comprehensively understand both conventional and CAM therapies, enabling them to provide patients with informed guidance regarding safe and efficacious treatment options, culminating in enhanced patient outcomes.

Contribution of Anti-p63 Antibodies in the Interpretation of Benign Label Prostatic Biopsies

Introduction: Prostate cancer is the second most common cancer in men. The diagnosis is most often based on the prostate biopsies’ analysis and on histological criteria recognizable on standard coloring. In some cases, the use of immunohistochemistry is important. Objectives: This paper aims to specify the p63 phenotypic profile of lesions diagnosed benign, with minimal suspect foci, difficult to interpret, HGPIN (high grade intraepithelial neoplasia) and LGPIN (low-grade prostatic intraepithelial neoplasia) and evaluate the manual technique of p63 immunohistochemistry. Patients and Method: This was a retrospective, descriptive study of prostate biopsies recorded in the PAC service of the HALD from January 1st, 2018 to December 31st, 2018. It was completed by a manual immunohistochemical study of the blocks enrolled from November 19th to December 4th, 2020 in the PAC department of the HPD. The studied parameters were: registry number, age, clinical stage, prostate volume, PSA level, microscopic appearance and p63 immunohistochemical profile. Results: Our study included 60 prostate biopsies. The ages of our patients varied from 45 to 77 years, with an average of 64.2 years and a standard deviation of 6.2. The majority of patients were at clinical stage cT2b (33%) with a prostate volume varying between 33.15 and 169.4 cc. The minimum value of PSA in our series is 5 ng/ml, the maximum being 100 ng/ml with an average level of 24.1 ng/ml and a standard deviation of 21.2. Our series included 50 adenomyomatous hyperplasias, 7 adenomyomatous hyperplasias associated with chronic prostatitis, 2 HGPIN and 1 LGPIN. After re-reading we found 5 discordant cases, which corresponded to minimal suspect foci (kappa = 0.5098). The p63 marking was informative in 53 cases, i.e. 88%, and non-informative in 7 cases, i.e. 12%. Among the uninformative markings, 2 were due to lack of tissue adhesion to the slides. Among the informative markings, 11 were negative. p63 immunohistochemistry was useful in all suspected foci and detected 6 other minimal foci of adenocarcinoma. Conclusion: The immunostaining with the anti-p63 antibody in the prostate cancer diagnosis is of considerable benefit. It made it possible to correct 11.3% of benign diagnosis in minimal malignant focus in our context. Despite the difficulties associated with the manual technique, it is possible to have an informative rate, similar to the automatic technique.

A Comprehensive Review of Exosomes with Therapeutic Potential in Cancer and Coeliac Disease

The aim of this review was to evaluate the therapeutic potential of exosomes, extracellular vesicles secreted by cells. They have emerged as potential therapeutic transporters for several diseases. This review provides an overview of exosomes’ therapeutic potential in cancer therapy and autoimmune conditions such as Coeliac Disease. The therapeutic effect is that the phospholipid-binding protein ANXA1 improves its anti-inflammatory properties. The review also analyzes the intricate processes of exosome production and composition ability to transport biomolecules such as proteins, microRNAs, and lipids, which promote intercellular communication and alter recipient cell behavior. Exosomes, linked to neurological disorders, cardiovascular disease, and cancer, present the means of targeted drug administration due to their innate specificity. Through genetic engineering and chemical modifications, exosomes can be tailored for specific purposes, demonstrating their versatility in targeted therapy. With ongoing research uncovering their therapeutic potential, exosomes present a promising frontier in novel medical treatments across various health conditions.

Content determination of benzyl glucosinolate and anti—cancer activity of its hydrolysis product in Carica papaya L.

Objective:To determine the content of benzyl glueosinolate（BG） in the pulp and the seed and investigate the anti-cuncer activity of its hydrolysis product in Curica papaya L.Methods: Determination of BG was performed on an Hypersil BDS C18 column at the wavelength of 214 nm with 0.1%trifluoroacelic acid（TFA） aqueous solution（A） and 0.1%TFA acelonilrile（B） as the mobile phase.In vitro activity test was adopted with cidtured human lung cancer H69 cell in vitro to investigate the inhibition rate of cell proliferation of benzyl isothiocyanale（BITC） againsl H69 cell.Results:The pulp has more BG before the maturation of papaya and it nearly disappeared after papaya matured,while the seed contains BG at every stage.Activity test demonstrated that the a higher concentration of BITC would have betler inhibition rate of cell proliferation on 1169 cell,and the IC50 was 6.5μmol/L.Conclusions:BG also can be produced in the pulp of papaya and it will be stored in the seed after the fruit has been matured.The hydrolysis product of BG has certain cancer-prevention anti-cancer activities for human.

Potential Anti-cancer Activity of Furanodiene

Objective： To study the isolated from the essential oil VIVO anti-tumor activities of furanodiene of the rhizome of Curcuma wenyujin （C15H200）, a primary sesquiterpene compound YH Chen et C. Ling（Wen Ezhu）, in vitro and in Methods： In vitro MTT assay was used to further study the effects of time and dosage on anti-proliferation of furanodiene against the sensitive Hela, Hep-2, HL-60, U251 cells, based on the cytotoxic effects of furanodiene on 12 human malignant tumor cell lines with the essential oil of Wen Ezhn as control., and the half-inhibitory concentration （IC50） was observed. In vivo uterine cervix （U14） tumor cell was selected and the conventional assay method of anti-tumor activity was employed. Furanodiene liposome was administered intraperitoneally, and tumor-inhibitory rate, thymus and spleen indexes were observed. Results： The inhibitive effects on cell proliferation were shown in all of the twelve cell lines and the cytotoxic effects of furanodiene against Hela, Hep-2, HL-60, U251 cells were observed after 12 h of administration, the effect could last for at least 48 h in a dose dependent manner, and the IC50 values were 0.6, 1.7, 1.8, 7.0μg/ml, respectively. Furanodiene was also found to show inhibitive effects on the proliferation of uterine cervix （U14） tumor induced in mice. The tumor inhibition rates were 36.09% （40 mg/kg）, 41.55% （60 mg/kg）, 58.29% （80 mg/kg）, respectively. Conclusion： Furanodiene is one of primary anti-cancer active components in the essential oil of Wen Ezhu, and also a very effective agent against uterine cervix cancer, and has protection effect on the immune function.

Effect of Yiqi Jianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role

Objective:To observe the effect of Yiqi Jianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role.Methods:Human intestinal cancer cell HT29 xenograft of nude mice model was established.The expression of ECF,VEGF,gastric cancer tumor growth in mice were observed.Results:Protein kinase C expression in in the Yiqi Jianpi group and Yiqi Jianpi anti-tumor group was significantly better than the model group(P<0.01,P<0.05).There was significantly more apoptotic cells in Yiqi Jianpi anti-tumor group than Yiqi Jianpi group and model group(P<0.01).Epidermal growth factor and vascular endothelial growth factor expression in Yiqi Jianpi group was significantly lower than Yiqi Jianpi group and model group(P<0.05).Conclusions:Tumor can inhibit the expression of PKC inhibition.Yiqi Jianpi and anticancer treatment can reduce this inhibition.Besides this treatment can also inhibit expression of tumor related genes such as epidermal growth factor and vascular endothelial growth factor.

Synthesis,Crystal Structure and in vitro Anticancer Studies of 1,2-Bis-benzimidazole-phenyl Copper(Ⅱ) Complex

One new benzimidazole derivative copper（II） complex 1（C10H6Cu N2, Mr = 217.71） has been synthesized and characterized by FT-IR and X-ray single-crystal diffraction. It crystallizes in orthorhombic, space group Pbcn with a = 17.417（2）, b = 8.9963（8）, c = 11.3432（9） ？, V = 1777.3（3） ？3, Z = 8, μ（Mo Kα） = 2.403, F（000） = 872, Dc = 1.627 g/cm3. The final R = 0.0598 for 1153 observed reflections with I 〉 2σ（I） and w R = 0.17 for all data. The in vitro anti-cancer activities of 1, Cu Cl2 and the benzimidazole ligand L were investigated using human cervical（Hela） and hepatocellular carcinoma（Hep-G2） cancer cell lines. The copper（II） complex can greatly inhibit the cell proliferation and show stronger cytotoxic activities against the tested cancer cell lines than both the ligand and copper（II） salt.

Quantitative Structure Anti-Cancer Activity Relationship (QSAR) of a Series of Ruthenium Complex Azopyridine by the Density Functional Theory (DFT) Method

A series of ruthenium azopyridine complexes have recently been investigated due to their potential cytotoxic activities against renal cancer (A498), lung cancer (H226), ovarian cancer (IGROV), breast cancer (MCF-7) and colon cancer (WIDR). Thus, in order to predict the cytotoxic potentials of these compounds, quantitative structure-activity relationship studies were carried out using the methods of quantum chemistry. Five Quantitative Structure Activity Relationship (QSAR) models were obtained from the determined quantum descriptors and the different activities. The models present the following statistical indicators: regression correlation coefficient R2 = 0.986 - 0.905, standard deviation S = 0.516 - 0.153, Fischer test F = 106.718 - 14.220, correlation coefficient of cross-validation = 0.985- 0.895 and = 0.010 - 0.001. The statistical characteristics of the established QSAR models satisfy the acceptance and external validation criteria, thereby accrediting their good performance. The models developed show that the variation of the free enthalpy of reaction , the dipole moment μ and the charge of the ligand in the complex Ql, are the explanatory and predictive quantum descriptors correlated with the values of the anti-cancer activity of the studied complexes. Moreover, the charge of the ligand is the priority descriptor for the prediction of the cytotoxicity of the compounds studied. Furthermore, QSAR models developed are statistically significant and predictive, and could be used for the design and synthesis of new anti-cancer molecules.

Anti-cancer effect of ethylacetate fraction from Orostachys japonicus on HT-29 human colon cancer cells by induction of apoptosis through caspase-dependent signaling pathway

Objective: To investigate the anti-colon cancer effects of ethylacetate fraction from Orostachys japonicus(0. japonicus) on HT-29 cancer cells. Methods: The viability of HT-29 cells was assayed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium(MTS) method. Apoptosis induction and cell cycle inhibition were confirmed by fluorescein isothiocyanate and propidium iodide staining using flow cytometry.Morphological changes in the nucleus were observed, using a fluorescence microscope with4',6-diamidino-2-phenylindole(DAPI) nuclear staining. The expression levels of the upstream and downstream proteins involved in the anti-cancer mechanism were confirmed by Western blotting. Results: After treating HT-29 cells with different concentrations of ethylacetate fraction from O. japonicus, the viability of cells decreased in a concentration-dependent manner,while apoptosis induction and apoptotic body formation increased. Cell cycle analysis showed that the arrest occurred at the sub-G_1 and S phase. Among the upstream and downstream proteins involved in anti-cancer activity, the level of B cell lymphoma-2 decreased, and the bcl-2-associated x protein increased. The level of pro-caspase-3, pro-caspase-8, and pro-caspase-9 decreased, while the level of cleaved-caspase-3, cleaved-caspase-8, and cleaved-caspase-9 increased. Moreover, the phosphorylation, that is, activation of extracellular signal regulated kinase 1/2, Jun-N-terminal kinase, and p38 increased. Conclusions: Combining the above results, it is thought that the survival of HT-29 cells is suppressed by ethylacetate fraction from0. japonicus through mitochondrial regulation-induced caspase cascade activation, induction of apoptosis and cell cycle arrest.

Combination Treatment with BEC and Cisplatin Synergistically Augments Anticancer Activity and Results in Increased Absolute Survival

Plant-derived BEC with its main component solamargine possesses anticancer activities via its effect on a variety of biological pathways in a wide range of human cancer cells. High cure rates with BEC therapy have been obtained in animals with deadly cancers, and, in humans with terminal cancers promising results have been reported. At a clinical level, optimal concentrations of BEC have been established in a topical cream formulation Curaderm, for effective removal of skin cancers, but optimal concentrations of BEC have not been reported for other cancers. The objective of this study was to determine whether combination therapy of Cisplatin with BEC would result in synergism using cure rates as end points. BEC on its own cures Sarcoma 180 in mice, whereas, Cisplatin on its own has no effect on Sarcoma 180 activity. A combination of BEC and Cisplatin shows synergism, resulting in higher cure rates than BEC and Cisplatin at comparable individual concentrations.

Machine Learning Prediction for 50 Anti-Cancer Food Molecules from 968 Anti-Cancer Drugs

Cancer-beating molecules (CBMs) are abundant in many types of food and potentially anti-cancer therapeutic agents. In the previous work, researchers introduced a network-based machine learning platform to identify the cancer-beating molecules, for example,?comparing the similarities in the molecular network between approved anticancer drug and food molecules. Herein, we aim to build on this work to enhance the accuracy of predicting food molecules. In this project, we improve supervised learning approaches by applying Soft Voting algorithm to seven machine learning algorithms: Support Vector Machine with Radial Basis Function (SVM with RBF kernel), multilayer perceptron neural network?(MLP), Random forest, Decision trees,?Gaussian Naive Bayes, Adaboosting, and Bagging. As a result, the accuracy in the dataset of 50 food molecules utilized increased from 82% to 87%, achieving a significant improvement in the precision of?predicting anti-cancer molecules.

HPLC Method Research of Picoplatin-a New Platinum Anti-cancer Drug and Its Impurities

Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-itrile as the mobile phase at a flow rate of 1.0 mL/min. The detecting wavelength was set at 210 nm, and the column temperature was set at 30℃. Result: in the method validation, the linear relationship modulus of picoplatin is 0.9999, the systemic precision is 0.44%, the method precision is 0.74%, the average recovery rate is 99.62%, the LOD and LOQ of picoplatin is 0.2 ng and 1.0 ng. The average resolution of picoplatin and its impurities is more than 2. Conclusion: The established method is good specificity, high sensitivity, and good repeatability which could provide scientific evidence for the quality control of picoplatin and its impurities.

Advances in Research on Anti-cancer Mechanism of 18β Glycyrrhetinic Acid

Glycyrrhiza uralensis Fisch has been used to treat the symptoms of organ fever, food poisoning, typhoid fever, sore throat, cough due to lung heat, children's diseases and so on since the ancient times. It is a solid Chinese herbal medicine which is good for the health. In recent years, it has been found that licorice extract also has excellent anti-cancer effect. The 18β glycyrrhetinic acid, obtained by hydrolysis of precursor glycyrrhizic acid, is a relatively efficient anti-cancer ingredient. 18β glycyrrhetinic acid can exert anti-cancer effects by inhibiting cancer cell proliferation, inducing apoptosis of cancer cells, inhibiting invasion and metastasis of cancer cells, preventing oxidation, inhibiting neovascularization, inhibiting lymphangiogenesis, and regulating hormone secretion. This paper reviewed the advances in research of the anticancer mechanism of 18β glycyrrhetinic acid, to provide a theoretical basis for future research.

Chinese Anti-Cancer Association as a non-governmental organization undertakes systematic cancer prevention work in China

Cancer has become the first leading cause of death in the world, particularly in low- and middle-income countries. Facing the increasing trend of cancer incidence and mortality, China issued and implemented ＂three-early（early prevention, early diagnosis and early treatment）＂ national cancer prevention plan. As the main body and dependence of social governance, non-governmental organizations（NGOs） take over the role of government in the field of cancer prevention and treatment. American Cancer Society（ACS） made a research on cancer NGOs and civil society in cancer control and found that cancer NGOs in developing countries mobilize civil society to work together and advocate governments in their countries to develop policies to address the growing cancer burden. Union for International Cancer Control（UICC）, Cancer Council Australia（CCA）, and Malaysian cancer NGOs are the representatives of cancer NGOs in promoting cancer control. Selecting Chinese Anti-Cancer Association（CACA） as an example in China, this article is to investigate how NGOs undertake systematic cancer prevention work in China. By conducting real case study, we found that, as a NGO, CACA plays a significant role in intensifying the leading role of government in cancer control, optimizing cancer outcomes, decreasing cancer incidence and mortality rates and improving public health.

Near-infrared photoimmunotherapy of pancreatic cancer using an indocyanine green-labeled anti-tissue factor antibody

AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.38(NIR-PIT) vs 5.42 ± 1.61(Untreated), vs 4.90 ± 0.87(NIR), vs 4.28 ±1.87(1849-ICG), vs 4.35 ± 1.42(anti-TF 1849), at Day 27, P < 0.05]. Tumors that received NIR-PIT showed evidence of necrotic cell death-associated features upon hematoxylin-eosin staining accompanied by a decrease in Ki-67-positive cells(a cell proliferation marker) by IHC examination.CONCLUSION The TF-targeted NIR-PIT with the 1849-ICG conjugate can potentially open a new platform for treatment of TF-expressing pancreatic cancer.

Carbohydrate-associated epitope-based anti-cancer drugs and vaccines

RP215 is one of the three thousand monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line. RP215 was shown to react with a carbohydrate-associated epitope located specifically on glycoproteins, known as CA215, from cancer cells. Further molecular analysis by matrix adsorption laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that CA215 consists mainly of immunoglobulin super-family (IgSF) proteins, including immunoglobulins, T-cell receptors, and cell adhesion molecules, as well as several other unrelated proteins. Peptide mappings and glycoanalysis were performed with CA215 and revealed high-mannose and complex bisecting structures with terminal sialic acid in N-glycans. As many as ten O-glycans, which are structurally similar to those of mucins, were also identified. In addition, two additional O-linked glycans were exclusively detected in cancerous immunoglobulins but not in normal B cell-derived immunoglobulins. Immunizations of mice with purified CA215 resulted in the predominant generation of RP215-related Mabs, indicating the immunodominance of this carbohydrate-associated epitope. Anti-idiotype (anti-id) Mabs of RP215, which were generated in the rat, were shown to contain the internal images of the carbohydrate-associated epitope. Following immunizations of these anti-id Mabs in mice, the resulting anti-anti-id (Ab3) responses in mice were found to be immunologically similar to that of RP215. Judging from these observations, anti-id Mabs, which carry the internal image of the RP215-specific epitope, may be suitable candidates for anticancer vaccine development in humans.

Does aspirin or non-aspirin non-steroidal anti-inflammatory drug use prevent colorectal cancer in inflammatory bowel disease?

AIM: To determine whether aspirin or non-aspirin nonsteroidal anti-inflammatory drugs(NA-NSAIDs) prevent colorectal cancer(CRC) in patients with inflammatory bowel disease(IBD).METHODS: We performed a systematic review and meta-analysis. We searched for articles reporting the risk of CRC in patients with IBD related to aspirin or NANSAID use. Pooled odds ratios(OR) and 95%CIs were determined using a random-effects model. Publication bias was assessed using Funnel plots and Egger's test. Heterogeneity was assessed using Cochran's Q and the I2 statistic.RESULTS: Eight studies involving 14917 patients and 3 studies involving 1282 patients provided data on the risk of CRC in patients with IBD taking NA-NSAIDs and aspirin respectively. The pooled OR of developing CRC after exposure to NA-NSAIDs in patients with IBD was 0.80(95%CI: 0.39-1.21) and after exposure to aspirin it was 0.66(95%CI: 0.06-1.39). There was significant heterogeneity(I2 > 50%) between the studies. There was no change in the effect estimates on subgroup a na ly s e s o f t he po pulat io n s t udie d o r w he t he r adjustment or matching was performed.CONCLUSION: There is a lack of high quality evidence on this important clinical topic. From the available evidence NA-NSAID or aspirin use does not appear to be chemopreventative for CRC in patients with IBD.