Search results for: nonsmall cell lung cancer

Authors: Amanina Iymia Jeffree, Reena Thriumani, Mohammad Iqbal Omar, Ammar Zakaria, Yumi Zuhanis Has-Yun Hashim, Ali Yeon Md Shakaff

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Metabolite profiling is a strategy to be approached in the pattern recognition method focused on three types of cancer cell line that driving the most to death specifically lung, breast, and colon cancer. The purpose of this study was to discriminate the VOCs pattern among cancerous and control group based on metabolite profiling. The sampling was executed utilizing the cell culture technique. All culture flasks were incubated till 72 hours and data collection started after 24 hours. Every running sample took 24 minutes to be completed accordingly. The comparative metabolite patterns were identified by the implementation of headspace-solid phase micro-extraction (HS-SPME) sampling coupled with gas chromatography-mass spectrometry (GCMS). The optimizations of the main experimental variables such as oven temperature and time were evaluated by response surface methodology (RSM) to get the optimal condition. Volatiles were acknowledged through the National Institute of Standards and Technology (NIST) mass spectral database and retention time libraries. To improve the reliability of significance, it is of crucial importance to eliminate background noise which data from 3rd minutes to 17th minutes were selected for statistical analysis. Targeted metabolites, of which were annotated as known compounds with the peak area greater than 0.5 percent were highlighted and subsequently treated statistically. Volatiles produced contain hundreds to thousands of compounds; therefore, it will be optimized by chemometric analysis, such as principal component analysis (PCA) as a preliminary analysis before subjected to a pattern classifier for identification of VOC samples. The volatile organic compound profiling has shown to be significantly distinguished among cancerous and control group based on metabolite profiling.

Keywords: in vitro cancer cell line, metabolite profiling, pattern recognition, volatile organic compounds

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Authors: Maxime Moreau, Silvère Baron, Jean-Marc Lobaccaro, Karine Charlet, Sébastien Menecier, Frédéric Perisse

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Cold Atmospheric Plasma (CAP) is an ionized gas generated at atmospheric pressure with the temperature of heavy particles (molecules, ions, atoms) close to the room temperature. Recent studies have shown that both in-vitro and in-vivo plasma exposition to many cancer cell lines are efficient to induce the apoptotic way of cell death. In some other works, normal cell lines seem to be less impacted by plasma than cancer cell lines. This is called selectivity of plasma. It is highly likely that the generated RNOS (Reactive Nitrogen Oxygen Species) in the plasma jet, but also in the medium, play a key-role in this selectivity. In this study, two CAP devices will be compared to electrical power, chemical species composition and their efficiency to kill cancer cells. A particular focus on the action of hydrogen peroxide will be made. The experiments will take place as described next for both devices: electrical and spectroscopic characterization for different voltages, plasma treatment of normal and cancer cells to compare the CAP efficiency between cell lines and to show that death is induced by an oxidative stress. To enlighten the importance of hydrogen peroxide, an inhibitor of H2O2 will be added in cell culture medium before treatment and a comparison will be made between the results of cell viability in this case and those from a simple plasma exposition. Besides, H2O2 production will be measured by only treating medium with plasma. Cell lines will also be exposed to different concentrations of hydrogen peroxide in order to characterize the cytotoxic threshold for cells and to make a comparison with the quantity of H2O2 produced by CAP devices. Finally, the activity of catalase for different cell lines will be quantified. This enzyme is an important antioxidant agent against hydrogen peroxide. A correlation between cells response to plasma exposition and this activity could be a strong argument in favor of the predominant role of H2O2 to explain the selectivity of plasma cancer treatment by cold atmospheric plasma.

Keywords: cold atmospheric plasma, hydrogen peroxide, prostate cancer, selectivity

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Authors: Zahra Shokrolahi, Mohammad Reza Atashzar

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The goals of treating patients with breast cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. The term of cellular immunotherapy refers to the administration of living cells to a patient; this type of immunotherapy can be active, such as a dendritic cell (DC) vaccine, in that the cells can stimulate an anti-tumour response in the patient, or the therapy can be passive, whereby the cells have intrinsic anti-tumour activity; this is known as adoptive cell transfer (ACT) and includes the use of autologous or allogeneic lymphocytes that may, or may not, be modified. The most important breast cancer cellular immunotherapies involving the use of T cells and natural killer (NK) cells in adoptive cell transfer, as well as dendritic cells vaccines. T cell-based therapies including tumour-infiltrating lymphocytes (TILs), engineered TCR-T cells, chimeric antigen receptor (CAR T cell), Gamma-delta (γδ) T cells, natural killer T (NKT) cells. NK cell-based therapies including lymphokine-activated killers (LAK), cytokine-induced killer (CIK) cells, CAR-NK cells. Adoptive cell therapy has some advantages and disadvantages some. TILs cell strictly directed against tumor-specific antigens but are inactive against tumor changes due to immunoediting. CIK cell have MHC-independent cytotoxic effect and also need concurrent high dose IL-2 administration. CAR T cell are MHC-independent; overcome tumor MHC molecule downregulation; potent in recognizing any cell surface antigen (protein, carbohydrate or glycolipid); applicable to a broad range of patients and T cell populations; production of large numbers of tumor-specific cells in a moderately short period of time. Meanwhile CAR T cells capable of targeting only cell surface antigens; lethal toxicity due to cytokine storm reported. Here we present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials .To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure.

Keywords: breast cancer , cell therapy , CAR T cell , CIK cells

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Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

Procedia PDF Downloads 217

Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

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Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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Authors: Ceyda Okudu, Secil Eroglu, Khandakar A. S. M. Saadat, Sibel O. Balci

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Ring Finger Protein 2 (RNF2) is a member of polycomb repressive complex 1 (PRC1), which is one of the epigenetic regulators in the genome. When RNF2 combines with other PRC1 members, it mediates the mono-ubiquitination of Histon2A (H2A). In breast cancer, RNF2 is commonly overexpressed, and also it promotes metastasis and invasion in other aggressive tumors like melanoma, prostate, and hepatocarcinoma. The role of RNF2 in the metastasis and invasion of breast cancer has not yet been elucidated. Our aim is to observe the role of RNF2 in metastasis and invasion in this study by miRNA mediated RNF2 gene silencing in breast cancer cell lines. We selected miRNAs, targeting to RNF2 by searching online databases. miR-17-5p, miR20a-5p, and miR-106b-5p were transfected to breast cancer cell lines (MCF-7, MDA-MB-231, SK-BR-3, and ZR-75-1), and also we used normal breast epithelial cell line (hTERT-HME1) to compare RNF2 gene expression level. After 48-72 hours post-transfection, mRNAs were isolated from the cells, and gene expressions were measured by RT-qPCR after from cDNA syntheses. We observed that RNF2 was highly expressed in SK-BR-3 and MDA-MB-231 cell lines opposite to MCF-7 and ZR-75-1 cell lines. RNF2 was downregulated 5, 5 and 7 fold by miR17-5p, miR20a-5p and miR106b-5p respectively in MCF-7. However, in SK-BR-3 and ZR-75-1 cell lines, miRNAs did not affect significantly RNF2 gene expression level. miR20a-5p decreased RNF2 3 fold and miR17-5p and miR106b-5p did not affect MDA-MB-231. After gene expression analysis, we performed metastasis and invasion assay in MCF-7 cells. For metastasis, we used both wound healing assay and Transwell Cell Migration Assay, and we used Transwell Cell Invasion Assay for invasion. The data of this assay showed that miR17-5p and miR20a-5p decreased both invasion and metastasis level, but miR106b-5p has no effect. We would like to conclude that RNF2 can be targeted by miR17-5p, miR20a-5p and miR106b-5p in MCF-7 cells and also RNF2, which is one of the upregulated genes in aggressive tumor, can be decreased by using these miRNAs. In future, we would like to confirm these results at the protein level and also whether these miRNAs are direct target of RNF2 or not.

Keywords: breast cancer, epigenetic, microRNAs, RNF2

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Authors: Srisopa Ruangnoo, Arunporn Itharat

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The ethanolic and aqueous extracts of Parkia javanica Merr. germinating seeds and Parkia speciosa Hassk. seeds were evaluated for cytotoxic activity against three different types of human cancer cell lines including colon cancer (LS174T), breast cancer (MCF-7) and prostate cancer (PC3) using sulforhodamine B (SRB) assay. The fresh plant parts were divided into 2 parts. The first part was extracted by maceration with 95% ethanol for 3 days and then filtered, and the filtrates were evaporated by rotary evaporator. The other part was squeezed and filtered. Then the filtrates were dried by freeze dryer. The screening found that the aqueous extract of P. javanica Merr. germinating seeds exhibited more than 70% inhibition (at concentration 50 µg/ml) against all types of human cancer cells. The aqueous extract of P. javanica Merr. germinating seeds showed the highest cytotoxic activity against MCF-7 with the IC50 value as 5.63 µg/ml. The aqueous extract of P. javanica Merr. germinating seeds also showed high cytotoxic activity against PC3 and LS174T with the IC50 values as 10.79 and 11.40 µg/ml, respectively. In conclusion, P. javanica Merr. germinating seed is a natural source of anticancer activity and further research to isolate active compounds from this plant should be undertaken.

Keywords: cytotoxic activity, Parkia javanica Merr., Parkia speciosa Hassk., human cancer cell lines

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Authors: Isaac Quiros-Fernandez, Angel Cid-Arregui

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Tumor-reactive T cell receptors (TCRs) are being subject of intense investigation since they offer great potential in adoptive cell therapies against cancer. However, the identification of tumor-specific TCRs has proven challenging, for instance, due to the limited expansion capacity of tumor-infiltrating T cells (TILs) and the extremely low frequencies of tumor-reactive T cells in the repertoire of patients and healthy donors. We have developed an approach for rapid identification and characterization of neoepitope-reactive TCRs from the T cell repertoire of healthy donors. CD8 T cells isolated from multiple donors are subjected to a first sorting step after staining with HLA multimers carrying the peptide of interest. The isolated cells are expanded for two weeks, after which a second sorting is performed using the same peptide-HLA multimers. The cells isolated in this way are then processed for single-cell sequencing of their TCR alpha and beta chains. Newly identified TCRs are cloned in appropriate expression vectors for functional analysis on Jurkat, NK92, and primary CD8 T cells and tumor cells expressing the appropriate antigen. We have identified TCRs specifically binding HLA-A2 presenting epitopes of tumor antigens, which are capable of inducing TCR-mediated cell activation and cytotoxicity in target cancer cell lines. This method allows the identification of tumor-reactive TCRs in about two to three weeks, starting from peripheral blood samples of readily available healthy donors.

Keywords: cancer, TCR, tumor antigens, immunotherapy

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Authors: Shouta Sora, Shizuki Kuriu, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

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Lymph node (LN) metastasis accounts for 20 - 30 % of all deaths in patients with head and neck cancer. Therefore, the control of metastatic lymph nodes (MLNs) is necessary to improve the life prognosis of patients with cancer. In a classical metastatic theory, tumor cells are thought to metastasize hematogenously through a bead-like network of lymph nodes. Recently, a lymph node-mediated hematogenous metastasis theory has been proposed, in which sentinel LNs are regarded as a source of distant metastasis. Therefore, the treatment of MLNs at the early stage is essential to prevent distant metastasis. Radiation therapy is one of the primary therapeutic modalities in cancer treatment. In addition, total body irradiation (TBI) has been reported to act as activation of natural killer cells and increase of infiltration of CD4+ T-cells to tumor tissues. However, the treatment effect of TBI for MLNs remains unclear. This study evaluated the possibilities of low-dose total body irradiation (L-TBI) and middle-dose total body irradiation (M-TBI) for the treatment of MLNs. Mouse breast cancer FM3A-Luc cells were injected into subiliac lymph node (SiLN) of MXH10/Mo/LPR mice to induce the metastasis to the proper axillary lymph node (PALN) and lung. Mice were irradiated for the whole body on 4 days after tumor injection. The L-TBI and M-TBI were defined as irradiations to the whole body at 0.2 Gy and 1.0 Gy, respectively. Tumor growth was evaluated by in vivo bioluminescence imaging system. In the non-irradiated group, tumor activities on SiLN and PALN significantly increased over time, and the metastasis to the lung from LNs was confirmed 28 days after tumor injection. The L-TBI led to a tumor growth delay in PALN but did not control tumor growth in SiLN and metastasis to the lung. In contrast, it was found that the M-TBI significantly delayed the tumor growth of both SiLN and PALN and controlled the distant metastasis to the lung compared with non-irradiated and L-TBI groups. These results suggest that the M-TBI is an effective treatment method for MLNs in the early stage and distant metastasis from lymph nodes via blood vessels connected with LNs.

Keywords: metastatic lymph node, lung metastasis, radiation therapy, total body irradiation, lymphatic system

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Authors: Ainoa Guinart, Maria Korpidou, Daniel Doellerer, Cornelia Palivan, Ben L. Feringa

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Stimuli responsive systems arise from the need to meet unsolved needs of current molecular drugs. Our study presents the design of a delivery system with high spatiotemporal control and tuneable release profiles. We study the incorporation of a hydrophobic synthetic molecular motor into PDMS-b-PMOXA block copolymer vesicles to create a self-assembled system. We prove their successful incorporation and selective activation by low powered visible light (λ 430 nm, 6.9 mW). We trigger the release of a fluorescent dye with high release efficiencies over sequential cycles (up to 75%) with the ability to turn on and off the release behaviour on demand by light irradiation. Low concentrations of photo-responsive units are proven to trigger release down to 1 mol% of molecular motor. Finally, we test our system in relevant physiological conditions using a lung cancer cell line and the encapsulation of an approved drug. Similar levels of cell viability are observed compared to the free-given drugshowing the potential of our platform to deliver functional drugs on demand with the same efficiency and lower toxicity.

Keywords: molecular motor, polymer, drug delivery, light-responsive, cancer, selfassembly

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Authors: Zoliana Bawitlung, P. C. Rohmingliana, L. Z. Chhangte, Remlal Siama, Hming Chungnunga, Vanram Lawma, L. Hnamte, B. K. Sahoo, B. K. Sapra, J. Malsawma

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Mizoram state has the highest lung cancer incidence rate in India due to its high-level consumption of tobacco and its products which is supplemented by the food habits. While smoking is mainly responsible for this incidence, the effect of inhalation of indoor radon gas cannot be discarded as the hazardous nature of this radioactive gas and its progenies on human population have been well-established worldwide where the radiation damage to bronchial cells eventually can be the second leading cause of lung cancer next to smoking. It is also known that the effect of radiation, however, small may be the concentration, cannot be neglected as they can bring about the risk of cancer incidence. Hence, estimation of indoor radon concentration is important to give a useful reference against radiation effects as well as establishing its safety measures and to create a baseline for further case-control studies. The indoor radon/thoron concentrations in Mizoram had been measured in 41 dwellings selected on the basis of spot gamma background radiation and construction type of the houses during 2015-2016. The dwellings were monitored for one year, in 4 months cycles to indicate seasonal variations, for the indoor concentration of radon gas and its progenies, outdoor gamma dose, and indoor gamma dose respectively. A time-integrated method using Solid State Nuclear Track Detector (SSNTD) based single entry pin-hole dosimeters were used for measurement of indoor Radon/Thoron concentration. Gamma dose measurements for indoor as well as outdoor were carried out using Geiger Muller survey meters. Seasonal variation of indoor radon/ thoron concentration was monitored. The results show that the annual average radon concentrations varied from 54.07 – 144.72 Bq/m³ with an average of 90.20 Bq/m³ and the annual average thoron concentration varied from 17.39 – 54.19 Bq/m³ with an average of 35.91 Bq/m³ which are below the permissible limit. The spot survey of gamma background radiation level varies between 9 to 24 µR/h inside and outside the dwellings throughout Mizoram which are all within acceptable limits. From the above results, there is no direct indication that radon/thoron is responsible for the high lung cancer incidence in the area. In order to find epidemiological evidence of natural radiations to high cancer incidence in the area, one may need to conduct a case-control study which is beyond this scope. However, the derived data of measurement will provide baseline data for further studies.

Keywords: background gamma radiation, indoor radon/thoron, lung cancer, seasonal variation

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Authors: Selim M. Khan, Aaron A. Goodarzi, Joshua M. Taron, Tryggve Rönnqvist

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Indoor air quality, a prime determinant of health, is strongly influenced by the presence of hazardous radon gas within the built environment. As a health issue, dangerously high indoor radon arose within the 20th century to become the 2nd leading cause of lung cancer. While the 21st century building metrics and human behaviors have captured, contained, and concentrated radon to yet higher and more hazardous levels, the issue is rapidly worsening in Canada. It is established that Canadians in the Prairies are the 2nd highest radon-exposed population in the world, with 1 in 6 residences experiencing 0.2-6.5 millisieverts (mSv) radiation per week, whereas the Canadian Nuclear Safety Commission sets maximum 5-year occupational limits for atomic workplace exposure at only 20 mSv. This situation is also deteriorating over time within newer housing stocks containing higher levels of radon. Deep machine learning (LSTM) algorithms were applied to analyze multiple quantitative and qualitative features, determine the most important contributory factors, and predicted radon levels in the known past (1990-2020) and projected future (2021-2050). The findings showed gradual downwards patterns in Sweden, whereas it would continue to go from high to higher levels in Canada over time. The contributory factors found to be the basement porosity, roof insulation depthness, R-factor, and air dynamics of the indoor environment related to human window opening behaviour. Building codes must consider including these factors to ensure adequate indoor ventilation and healthy living that can prevent lung cancer in non-smokers.

Keywords: radon, building metrics, deep learning, LSTM prediction model, lung cancer, canada, sweden

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Authors: Eun-Joong Kim, Sankarprasad Bhuniya, Hyunseung Lee, Hyun Min Kim, Chaejoon Cheong, Su-khendu Maiti, Kwan Soo Hong, Jong Seung Kim

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Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential anti-metastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2 selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug 7 showed effective anti-tumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anti-cancer drug, SN-38.

Keywords: hydrogen peroxide, prodrug, metastatic tumors, fluorescence

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Authors: Christy M. Moen, Richard B. Townsley

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Introduction: Metastasis to the frontal bone in thyroid cancer is extremely rare. A literature review found only six cases of thyroid cancer that metastasised to the frontal bone, with two of those involving further bone sites. Case Report: The patient was originally referred to the Oral and Maxillofacial Surgery team with an isolated mass on her forehead. Biopsies were performed, which showed this was likely a metastatic deposit from thyroid cancer. CT-PET scan showed this was an isolated lesion. The patient had a total thyroidectomy, and the forehead lesion was managed with radiotherapy. On interval scanning, the patient’s bony lesion had increased in size and had new lung nodules, which likely represented further metastasis. Conclusion: Isolated bony metastases to the frontal bone are rare. An important clinical principle to remember is that a bony metastasis from an unknown primary is more likely than primary bone cancer.

Keywords: cancer, thyroid, head and neck, surgery

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Authors: Nitesh Kumar, Eoin Twohig, jasparl cheema, Sadiq mawji, Yousif al najjar

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Basal cell carcinoma (BCC) is the commonest cutaneous malignancy affecting humans. Despite this, distant spread is exceptionally rare. Metastatic BCC (mBCC) is estimated to occur in 0.0028 - 0.5%. it aim to illustrate with the aid of histological slides, a case of mBCC occurring in a fit and well 67-year-old. Initial diagnosis of desmoplastic BCC was made in 2006 from a scalp biopsy with the lesion then being excised. Re-excision of local recurrence was undertaken the following year. In 2014 the patient presented with an ipsilateral level 2a mass. Fine Needle Aspiration raised the suspicion of metastatic carcinoma. The patient had excision of two nodes from the left neck alongside pharyngeal tonsillectomy and tongue base biopsies. Histologically, the nodes closely resembled the immunophenotype of the initial scalp lesion. The patient subsequently had a modified radical neck dissection, and residual mBCC was excised from the left Sternocleidomastoid muscle. In 2023 the patient developed haematuria. On further investigation bilateral lung lesions on CT were noted with subsequent biopsy confirming mBCC. Spinal and renal lesions have also been found. Histopathology showed clear resemblance of the lung metastases to both those in the neck and the primary (scalp BCC) – with no squamous differentiation seen. The time span from primary to occurrence of lung metastasis (18 years) affirms the indolent and slow growing nature of BCC.  This case fulfils Lattes and Kessler diagnostic criteria. High risk cases are described as those with advanced local presentation, primary tumour on the Head and Neck and locally recurrent lesions.

Keywords: BCC, metastasis, rare, skin cancer

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Authors: Hien Thi Thu Le, Nuno Rafael Candeias, Olli Yli-Harja, Meenakshisundaram Kandhavelu

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Purinergic receptor 1 (P2Y1R) is the potential therapeutic target for inducing prostate cancer (PCa) cell death. Recently, 1-indolinoalkyl 2-phenolic derivative, HIC, was identified as a P2Y1R agonist that increases apoptosis and inhibits cell proliferation of PCa. However, the biological effects of HIC have not been extensively studied at the molecular level. In the present study, we have investigated the anticancer effects of HIC and the molecular mechanisms underlying in PCa cells. Half maximal inhibitory concentration (IC₅₀) of HIC was measured as 15.98 μM and 15.64 μM for DU145 and PC3 cells, respectively. In addition, we found that HIC inhibited cell growth and metastasis of PC3 and DU145 cells colonies, spheroid areas, and migrated cells. RNA seq analysis revealed significant changes of over 3000 genes (p value < 0.05) upon HIC treatment in PC3 and DU145 cells. Genes involved in DNA damage, apoptosis, cell cycle arrest at G1/S phase were modulated by HIC treatment. MAPK and NF-κB protein array revealed the increased expression of ERK1/2, JNK1/2, p53 phosphorylation, and p53 protein. ERK1/2 and JNK1/2 activations are known to increase the stabilization of p53, a tumor suppressor protein, which is required to arrest the cell cycle at G1/S phase and cause cell death of PCa cells. Overall, our results suggest that HIC can serve as a multi-dimensional chemotherapeutic agent possessing strong cytotoxic, anti-cancer, and anti-metastasis against PCa growth.

Keywords: prostate cancer, P2Y1 receptor, apoptosis, metastasis

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Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

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Authors: Ming Ze Kao

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Static magnetic fields (SMF) are widely used in several medical applications, especially in diagnosis of tumors. However, biological effects of the SMFs on modulating cell physiology through the Lorentz force, which is highly frequency and magnitude dependent, remain to be elucidated. Specific patterns from SMFs of static MF, delivered by means of Halbach array magnets with a gradient increment of 6.857mT/mm from center to border, were found to have profound inhibitory effect on the growth rate of human cell line derived from Nasopharyngeal carcinoma patients. The SMFs, which were shown to be noncontact, selectively impact rapid dividing cells while quiescent cells stay intact. The phenomenon acts in two modes: the arrest of cell proliferation in the G2/M phase and destruction of cell mitosis in cell division. First mode is manifested by impacting the proper formation of mitotic spindle, whereas the second results in disintegration of the cancer cell. Both modes are demonstrated when SMF was applied for 24 hours to cancer cells, the results revealed that metaphase arrest during mitosis due to activation of DNA damage response (DDR), resulting in high expression of ATM-NBS1-CHEK signaling pathways and higher G2/M phase ratio compared with control group. Here, experimental data suggest that the SMFs cause activation of cell cycle checkpoints, which implies the MFs as a potential therapeutic modality as a sensitizer for radiotherapy or chemotherapy.

Keywords: static magnetic field, DNA damage response, Halbach array, magnetic therapy

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Authors: Maryam Zahedi Fard, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

Abstract:

New quinazoline schiff base 3-(5-bromo-2-hydroxy-3-methoxybenzylideneamino)-2-(5-bromo-2-hydroxy-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one was investigated for anticancer activity against MCF-7 human breast cancer cell line with involved mechanism of apoptosis. The compound demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41 ± 0.34, after 72 hours of treatment. Morphological apoptotic features in treated MCF-7 cells were observed by AO/PI staining. Furthermore, treated MCF-7 cells subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity test demonstrated the nontoxic nature of the compound in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potent candidate for further in vivo and clinical breast cancer studies.

Keywords: antiproliferative effect, MCF-7 human breast cancer cell line, apoptosis, caspases

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Authors: Sahar Heidary

Abstract:

Breast cancer is a main public common obstacle global. Additionally, it is the second top reason for tumor death across women. Considering breast cancer cure choices can aid private doctors in precaution for their patients through future cancer treatment. This article reviews usual management centered on stage, histology, and biomarkers. The growth of breast cancer is a multi-stage procedure including numerous cell kinds and its inhibition residues stimulating in the universe. Timely identification of breast cancer is one of the finest methods to stop this illness. Entirely chief therapeutic administrations mention screening mammography for women aged 40 years and older. Breast cancer metastasis interpretations for the mainstream of deaths from breast cancer. The discovery of breast cancer metastasis at the initial step is essential for managing and estimate of breast cancer development. Developing methods consuming the exploration of flowing cancer cells illustrate talented outcomes in forecasting and classifying the initial steps of breast cancer metastasis in patients. In public, mammography residues are the key screening implement though the efficiency of medical breast checks and self-checkup is less. Innovative screening methods are doubtful to exchange mammography in the close upcoming for screening the overall people.

Keywords: breast cancer, screening, metastasis, methods

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Authors: Merry Meryam Martgrita, Marselina Irasonia Tan

Abstract:

One of several aggresive cancer is cancer that overexpress c-erbB2 receptor along with the expression of estrogen receptor. Components of extracellular matrix play an important role to increase cancer cells proliferation, migration and invasion. Both components can affect cancer development by regulating the signal transduction pathways in cancer cells. In recent research, SKOV-3 ovarian cancer cell line, that overexpress c-erbB2 receptor was cultured on type IV collagen and treated with estradiol-17β, to reveal the role of both components on RNA and protein level of c-erbB2 receptor. In this research we found a modulation phenomena of increasing and decreasing of c-erbB2 RNA level and a stabilisation phenomena of c-erbB2 protein expression due to estradiol-17β and type IV collagen. It seemed that estradiol-17β has an important role to increase c-erbB2 transcription and the stability of c-erbB2 protein expression. Type IV collagen has an opposite role. It blocked c-erbB2 transcription when it bound to integrin receptor in SKOV-3 cells.

Keywords: c-erbB2, estradiol-17β, SKOV-3, type IV collagen

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Authors: I. Ramalho, S. Campos, M. Dias

Abstract:

Introduction: Endometriosis may play a role in the pathogenesis of ovarian cancer (OC), however, the risk and prognosis have not been well established. The association between these two pathologies could have an important impact on prevention and early diagnosis of OC. Objective: To analyze the prevalence of endometriosis associated ovarian cancer and related clinical, epidemiological and histopathological issues. Design: We conducted a retrospective case series analysis of patients diagnosed with endometriosis and ovarian cancer in the Gynecology Department of Coimbra University Hospital Center since 2006 to 2015. Methods: We collected data from women diagnosed with ovarian cancer, with anatomopathology records reporting findings of endometriosis in ovarian cancer patients. Patients were retrieved from the pathological records and appropriate medical records were retrospectively reviewed. Statistical analysis was performed using SPSS 22.0. Results: Histological evidence of endometriosis was found in 17 out of 261 patients diagnosed with ovarian cancer (OC) (6.51%). The most usual symptoms were pelvic pain, abdominal distension, asthenia, ascites, weight loss and nausea. Mean age at diagnosis was 61.2 ± 15.1, 41-86 years old, 33.3% were pre-menopausal patients and cancer stage distribution was predominantly stage I (31.3%) and stage III (56.3%). OC occurred unilaterally in 14 patients and 2 patients were diagnosed with a synchronous ovarian and endometrial cancer. Regarding histological type, 10 OC were classified as clear cell carcinoma (CCC), 4 endometrioid carcinomas (EC) and 3 mixed type (clear cell and endometrioid). Four ovarian carcinomas presumably arose from endometriomas: 3 CCC and 1 EC. Conclusions: In accordance with previous studies, clear cell was the most common pathological type in endometriotic patients, followed by endometrioid carcinomas, and two rare synchronous ovarian and endometrial carcinomas were registered. Although endometriosis association to OC is uncommon, endometriosis should be managed with special care in order to early diagnosis.

Keywords: endometriosis, histology, observational study, ovarian cancer

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Authors: Zaheer Ahmad, Afzal Shah

Abstract:

pH responsive block copolymers consist of mPEG and glutamic acid units were syntheiszed in different formulations. The synthesized polymers were structurally investigated. Doxorubicin Hydrocholide (DOX-HCl) as a chemotherapy medication for the treatment of cancer was selected. DOX-HCl was loaded and their drug loading content and drug loading efficiency were determined. The nanocarriers were obtained in small size, well shaped and slightly negative surface charge. The release study was carried out both at pH 7.4 and 5.5 and it was revealed that the release was sustained and in controlled manner and there was no initial burst release. The in vitro release study was further carried out for different formulations with different glutamic acid moieties. Time dependent cell proliferation inhibition of the free drug and drug loaded nanoparticles against human breast cancer cell lines MCF-7 and Zr-75-30 was observed. Cellular uptakes and endocytosis were investigated by confocal laser scanning microscopy (CLSM) and flow cytometery. The biocompatibility, optimum size, shape and surface charge of the developed nanoparticles make the nanoparticles an efficient drug delivery carrier.

Keywords: doxorubicin, glutamic acid, cell proliferation inhibition, breast cancer cell

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Authors: Helen Zhang

Abstract:

Accurate segmentation of the airways from CT scans is crucial for early diagnosis of lung cancer. However, the existing airway segmentation algorithms often rely on thin-slice CT scans, which can be inconvenient and costly. This paper presents a set of machine learning-based 3D super-resolution algorithms along heterogeneous dimensions to improve the resolution of thicker CT scans to reduce the reliance on thin-slice scans. To evaluate the efficacy of the super-resolution algorithms, quantitative assessments using PSNR (Peak Signal to Noise Ratio) and SSIM (Structural SIMilarity index) were performed. The impact of super-resolution on airway segmentation accuracy is also studied. The proposed approach has the potential to make airway segmentation more accessible and affordable, thereby facilitating early diagnosis and treatment of lung cancer.

Keywords: 3D super-resolution, airway segmentation, thin-slice CT scans, machine learning

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Authors: Piamsiri Sawaisorn, Tienrat Tangchaikeeree, Waraporn Chan-On, Chaniya Leepiyasakulchai, Rachanee Udomsangpetch, Suradej Hongeng, Kulachart Jangpatarapongsa

Abstract:

Human Vγ9Vδ2 T lymphocytes are regarded as promising effector cells for cancer immunotherapy since they have the ability to eliminate several tumor cells through non-peptide antigen recognition and non-major histocompatibility complex (MHC) restriction. An issue of recent interest is the capability to activate γδ T cells by use of a group of drugs, such as pamidronate, that cause accumulation of phosphoantigen which is recognized by γδ T cell receptors. Moreover, their antigen presenting cell-like phenotype and function have been confirmed in many clinical trials. In this study, Vγ9Vδ2 T cells derived from normal peripheral blood mononuclear cells were activated with pamidronate and the expanded Vγ9Vδ2 T cells can recognize and kill chronic myeloid leukemia (CML) cells treated with pamidronate through their cytotoxic activity. To support the strong role played by Vγ9Vδ2 T cells against cancer, we provide the evidence that Vγ9Vδ2 T cells activated with CML cell lysate antigen can efficiently express antigen presenting cell (APC) phenotype and function. In conclusion, pamidronate can be used in intentional activation of human Vγ9Vδ2 T cells and can increase the susceptibility of CML cells to cytotoxicity of Vγ9Vδ2 T cells. The activated Vγ9Vδ2 T cells by cancer cells lysate can show their APC characteristics, and so greatly increase the interest in exploring their therapeutic potential in hematologic malignancy.

Keywords: γδ T lymphocytes, antigen-presenting cells, chronic myeloid leukemia, cancer, immunotherapy

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Authors: Mohammad M. Aria, Fatma Öz, Yashar Esmaeilian, Marco Carofiglio, Valentina Cauda, Özlem Yalçın

Abstract:

Photoelectrical stimulation of cells with semiconductor organic polymers have been shown promising applications in neuroprosthetics such as retinal prosthesis. Photoelectrical stimulation of the cell membranes can be induced through a photo-electric charge separation mechanism in the semiconductor materials, and it can alter intracellular calcium level through both stimulation of voltage-gated ion channels and increase of intracellular reactive oxygen species (ROS) level. On the other hand, targeting voltage-gated ion channels in cancer cells to induce cell apoptosis through calcium signaling alternation is an effective mechanism which has been explained before. In this regard, remote control of the voltage-gated ion channels aimed to alter intracellular calcium by using photo-active organic polymers can be novel technology in cancer therapy. In this study, we used P (ITO/Indium thin oxide)/P3HT(poly(3-hexylthiophene-2,5-diyl)) and PN (ITO/ZnO/P3HT) photovoltaic junctions to stimulate MDA-MB-231 breast cancer cells. We showed that the photo-stimulation of breast cancer cells through photo capacitive current generated by the photovoltaic junctions are able to excite the cells and alternate intracellular calcium based on the calcium imaging (at 8mW/cm² green light intensity and 10-50 ms light durations), which has been reported already to safety stimulate neurons. The control group did not undergo light treatment and was cultured in T-75 flasks. We detected 20-30% cell death for ITO/P3HT and 51-60% cell death for ITO/ZnO/P3HT samples in the light treated MDA-MB-231 cell group. Western blot analysis demonstrated poly(ADP-ribose) polymerase (PARP) activated cell death in the light treated group. Furthermore, Annexin V and PI fluorescent staining indicated both apoptosis and necrosis in treated cells. In conclusion, our findings revealed that the photoelectrical stimulation of cells (through long time overstimulation) can induce cell death in cancer cells.

Keywords: Ca²⁺ signaling, cancer therapy, electrically excitable cells, photoelectrical stimulation, voltage-gated ion channels

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Authors: G. Eom, H. Kim, A. Hwang, T. Kang, B. Kim

Abstract:

Telomerase activity is overexpressed in over 85% of human cancers while suppressed in normal somatic cells. Telomerase has been attracted as a universal cancer biomarker. Therefore, the development of effective telomerase activity detection methods is urgently demanded in cancer diagnosis and therapy. Herein, we report a nanogap-rich Au nanowire (NW) surface-enhanced Raman scattering (SERS) sensor for detection of human telomerase activity. The nanogap-rich Au NW SERS sensors were prepared simply by uniformly depositing nanoparticles (NPs) on single-crystalline Au NWs. We measured SERS spectra of methylene blue (MB) from 60 different nanogap-rich Au NWs and obtained the relative standard deviation (RSD) of 4.80%, confirming the superb reproducibility of nanogap-rich Au NW SERS sensors. The nanogap-rich Au NW SERS sensors enable us to detect telomerase activity in 0.2 cancer cells/mL. Furthermore, telomerase activity is detectable in 7 different cancer cell lines whereas undetectable in normal cell lines, which suggest the potential applicability of nanogap-rich Au NW SERS sensor in cancer diagnosis. We expect that the present nanogap-rich Au NW SERS sensor can be useful in biomedical applications including a diverse biomarker sensing.

Keywords: cancer biomarker, nanowires, surface-enhanced Raman scattering, telomerase

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Authors: Rudra Prasad Khanal

Abstract:

Introduction: Non-communicable disease, such as cancer, has spread all over the world for some last decades. However, every nation has experienced a burden from the development of technology. In the context of Nepal, 10 to 15 thousand new cancer incidences are being registered in different hospitals for treatment. Since the date of starting nuclear medicine at Bir Hospital in 1998, cancer patients have been getting treatment regularly. According to the data of the population-based cancer registry, approximately 60% of the population having a middle-class income is being affected by cancer in Nepal. Methods and Materials: The study is aimed to find out the particular place where the population density of new cancer incidence is highest in Nepal and to inform the concerned regulatory body that is working on cancer screening and early detection for the proper treatment from the beginning. In order to identify the areas with the highest population density of new cancer incidence, all the data of cancer patients were collected from five different renowned hospitals and also from the population-based cancer registry center and then analyzed the data. The history of cancer patients was studied from 2003 to 2020, but here the data are analyzed from 2015 to 2020 only to find the latest trend in cancer incidence. Results: In the five major hospitals in Nepal, the total new cancer incidence was 61783 from 2015 to 2020. Out of those, 34617 were female, and 27176 were male. This research shows that female cancer patients were more every year. In the male, lung cancer patients more than cancer of other organs, but in females, the number of breast cancer patients was greatest. The age-adjusted mortality rate for males in Kathmandu valley was 36.3, and for females was 27.0 per 100,000 population. The cancer incidence and mortality rate were slightly lesser in other districts of Nepal. This rate increased with the increase in the age of people. Over 60 years, cancer incidence and mortality rates have been found to increase rapidly. Conclusion: This research supports conducting the program of cancer screening and early detection at Kathmandu valley with high priority and then Morang, Rukum, SSDM, etc., to control cancer.

Keywords: cancer incidence, research scholar, Tribhuvan University, Bhaktapur Cancer Hospital, Nepal

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Authors: Ramin Mehdiabadi

Abstract:

Background: Breast cancer remains the most prevalent cancer diagnosis and the leading cause of cancer death among women globally, representing 11.7% of new cases and 6.9% of deaths. While the incidence and mortality of major cancers are declining in developed regions like the United States and Western Europe, underdeveloped and developing countries exhibit an increasing trend, attributed to lifestyle factors such as smoking, physical inactivity, and high-calorie diets. Objective: This study explores the intricate relationship between the mammalian transcription factor forkhead box (FoxM1) and the microRNA miR-216b-5p in various subtypes of breast cancer, aiming to deepen the understanding of their roles in tumorigenesis, metastasis, and drug resistance. Methods: Breast cancer subtypes were categorized based on key biomarkers: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. These include luminal A, luminal B, HER2 enriched, triple-negative, and normal-like subtypes. We focused on analyzing the expression levels of FoxM1 and miR-216b-5p, given the known role of FoxM1 in cell proliferation and its implications in cancer pathologies such as lung, gastric, and breast cancers. Concurrently, miR-216b-5p's function as a tumor suppressor was evaluated to ascertain its regulatory effects on FoxM1. Results: Preliminary data indicate a nuanced interplay between FoxM1 and miR-216b-5p, suggesting a potential inverse relationship that varies across breast cancer subtypes. This relationship underscores the dual role of these biomarkers in modulating cancer progression and response to treatments. Conclusion: The findings advocate for the potential of miR-216b-5p to serve as a prognostic biomarker and a therapeutic target, particularly in subtypes where FoxM1 is prominently expressed. Understanding these molecular interactions provides crucial insights into the personalized treatment strategies and could lead to more effective therapeutic interventions in breast cancer management. Implications: The study highlights the importance of molecular profiling in breast cancer treatment and emphasizes the need for targeted therapeutic approaches in managing diverse cancer subtypes, particularly in varying global contexts where lifestyle factors significantly impact cancer dynamics.

Keywords: breast cancer, gene expression, FoxM1, microRNA

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Authors: M. Rahimnejad, B. Vahidi, B. Ebrahimi Hoseinzadeh, F. Yazdian, P. Motamed Fath, R. Jamjah

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In this study, we developed and simulated nano-drug delivery systems efficacy in compare to free drug prescription. Computational models can be utilized to accelerate experimental steps and control the experiments high cost. Molecular dynamics simulation (MDS), in particular NAMD was utilized to better understand the anti-cancer drug interaction with cell membrane model. Paclitaxel (PTX) and dipalmitoylphosphatidylcholine (DPPC) were selected for the drug molecule and as a natural phospholipid nanocarrier, respectively. This work focused on two important interaction parameters between molecules in terms of center of mass (COM) and van der Waals interaction energy. Furthermore, we compared the simulation results of the PTX interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane. The molecular dynamic analysis resulted in low energy between the nanocarrier and the cell membrane as well as significant decrease of COM amount in the nanocarrier and the cell membrane system during the interaction. Thus, the drug vehicle showed notably better interaction with the cell membrane in compared to free drug interaction with the cell membrane.

Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier

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