Search results for: metastatic squamous cell carcinoma

Authors: Maria E. V. Amarante, Carolina L. Cerdeira, Julia V. Cortes, Fiorita G. L. Mundim

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Basal cell carcinoma (BCC) is the most prevalent type of skin cancer in humans. It arises from the basal cells of the epidermis and cutaneous appendages. The role of sunlight exposure as a risk factor for BCC is very well defined due to its power to influence genetic mutations, in addition to having a suppressor effect on the skin immune system. Despite showing low metastasis and mortality rates, the tumor is locally infiltrative, aggressive, and destructive. Considering the high prevalence rate of this carcinoma and the importance of early detection, a retrospective study was carried out in order to correlate the clinical data available on BBC, characterize it epidemiologically, and thus enable effective prevention measures for the population. Data on the period from January 2015 to December 2019 were collected from the medical records of patients registered at one pathology service located in the southeast region of Brazil, known as SVO, which delivers skin biopsy results. The study was aimed at correlating the variables, sex, age, and subtypes found. Data analysis was performed using the chi-square test at a nominal significance level of 5% in order to verify the independence between the variables of interest. Fisher's exact test was applied in cases where the absolute frequency in the cells of the contingency table was less than or equal to five. The statistical analysis was performed using the R® software. Ninety-three basal cell carcinoma were analyzed, and its frequency in the 31-to 45-year-old age group was 5.8 times higher in men than in women, whereas, from 46 to 59 years, the frequency was found 2.4 times higher in women than in men. Between the ages of 46 to 59 years, it should be noted that the sclerodermiform subtype appears more than the solid one, with a difference of 7.26 percentage points. Reversely, the solid form appears more frequently in individuals aged 60 years or more, with a difference of 8.57 percentage points. Among women, the frequency of the solid subtype was 9.93 percentage points higher than the sclerodermiform frequency. In males, the same percentage difference is observed, but sclerodermiform is the most prevalent subtype. It is concluded in this study that, in general, there is a predominance of basal cell carcinoma in females and in individuals aged 60 years and over, which demonstrates the tendency of this tumor. However, when rarely found in younger individuals, the male gender prevailed. The most prevalent subtype was the solid one. It is worth mentioning that the sclerodermiform subtype, which is more aggressive, was seen more frequently in males and in the 46-to 59-year-old range.

Keywords: basal cell carcinoma, epidemiology, sclerodermiform basal cell carcinoma, skin cancer, solar radiation, solid basal cell carcinoma

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Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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Authors: B. Thanasansomboon, S. Choemprayong, N. Parinyanitikul, U. Tanlamai

Abstract:

Being diagnosed with metastatic breast cancer, the patients as well as their caretakers are affected physically and mentally. Although the medical systems in Thailand have been attempting to improve the quality and effectiveness of the treatment of the disease in terms of physical illness, the success of the treatment also depends on the quality of mental health. Metastatic breast cancer patients have found that social support is a key factor that helps them through this difficult time. It is recognized that social support in different dimensions, including emotional support, social network support, informational support, instrumental support and appraisal support, are contributing factors that positively affect the quality of life of patients in general, and it is undeniable that social support in various forms is important in promoting the quality of life of metastatic breast patients. However, previous studies have not been dedicated to investigating their quality of life concerning affective, cognitive, and behavioral outcomes. Therefore, this study aims to develop integrated social support through social networks to improve the quality of life of metastatic breast cancer patients in Thailand.

Keywords: social support, metastatic breath cancer, quality of life, social network

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Authors: Diwei Lin, Amanda Jh. Tan

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We present a very rare case of de novo large cell neuroendocrine carcinoma of the prostate (LCNEC) in an 84-year-old male on a background of high-grade, muscle-invasive transitional cell carcinoma of the bladder. While NE tumours account for 1% to 5% of all cases of prostate cancer and scattered NE cells can be found in 10% to 100% of prostate adenocarcinomas, pure LCNEC of the prostate is extremely rare. Most LCNEC of the prostate is thought to originate by clonal progression under the selection pressure of therapy and refractory to long-term hormonal treatment for adenocarcinoma of the prostate. De novo LCNEC is only described in case reports and is thought to develop via direct malignant transformation. Limited data in the English literature makes it difficult to accurately predict the prognosis of LCNEC of the prostate. However, current evidence suggesting that increasing NE differentiation in prostate adenocarcinoma is associated with a higher stage, high-grade disease, and a worse prognosis.

Keywords: large cell neuroendocrine cancer, prostate cancer, refractory cancer, medical and health sciences

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Authors: Hala M. El-hanbuli, Mohammed F. Darweesh

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The incidence rates of any tumor vary hugely with geographical location. Basal Cell Carcinoma (BCC) is one of the most common skin cancer that has many histopathologic subtypes. Objective: The aim was to study the histopathological features of BCC cases that were received in the Pathology Department, Kasr El-Aini hospital, Cairo University, Egypt during the period from Jan 2004 to Dec 2013 and to evaluate the clinical characters through the patient data available in the request sheets. Methods: Slides and data of BCC cases were collected from the archives of the pathology department, Kasr El-Aini hospital. Revision of all available slides and histological classification of BCC according to WHO (2006) was done. Results: A total number of 310 cases of BCC representing about 65% from the total number of malignant skin tumors examined during the 10-years duration in the department. The age ranged from 8 to 84 years, the mean age was (55.7 ± 15.5). Most of the patients (85%) were above the age of 40 years. There was a slight male predominance (55%). Ulcerated BCC was the most common gross picture (60%), followed by nodular lesion (30%) and finally the ulcerated nodule (10%). Most of the lesions situated in the high-risk sites (77%) where the nose was the most common site (35%) followed by the periocular area (22%), then periauricular (15%) and finally perioral (5%). No lesion was reported outside the head. The tumor size was less than 2 centimeters in 65% of cases, and from 2-5 centimeters in the lesions' greatest dimension in the rest of cases. Histopathological reclassification revealed that the nodular BCC was the most common (68%) followed by the pigmented nodular (18.75%). The histologic high-risk groups represented (7.5%) about half of them (3.75%) being basosquamous carcinoma. The total incidence for multiple BCC and 2nd primary was 12%. Recurrent BCC represented 8%. All of the recurrent lesions of BCC belonged to the histologic high-risk group. Conclusion: Basal Cell Carcinoma is the most common skin cancer in the 10-year survey. Histopathological diagnosis and classification of BCC cases are essential for the determination of the tumor type and its biological behavior.

Keywords: basal cell carcinoma, high risk, histopathological features, statistical analysis

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Authors: Shan-Ying Wu, Sheng-Hui Lan, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu

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In hepatocelluar carcinoma (HCC), dysregulated expression of cyclin D1 and impaired autophagy has been reported separately. However, the relationship between them has not been explored. In this study, we demonstrated that autophagy was inversely correlated with cyclin D1 expression in 147 paired HCC patient specimens. HCC specimen with highly expression of cyclin D1 shows correlation with poor overall survival rate. Furthermore, induction of autophagy by amiodarone (antiarrhythmic drug) in Hep 3B cells, cyclin D1 was recruited into autophagosomes demonstrated by immune-gold labeling of cyclin D1 after extraction of autophagosomes. We further demonstrated that autophagy suppresses Hep 3B cell proliferation, and further analysis revealed that cell cycle was arrested at G1 phase. The interaction between LC3 (maker of autophagy) and cyclin D1 was increased after autophagy induction. In addition, ubiquitinated-cyclin D1 was also increased after autophagy induction, which is selectively degraded by autophagosome through binding with SQSTM1/p62 (an adaptor protein). In vivo study showed that amiodarone induced autophagy suppresses liver tumor formation in xenograft mouse and orthotopic rat model through decreasing cyclin D1 expression and inhibition of cell proliferation. Altogether, we reveal a novel mechanism that ubiquitinated cyclin D1 degraded by autophagic pathway by p62 and amiodarone is a promising drug for targeting cyclin D1 in liver cancer therapy.

Keywords: autophagy, cyclin D1, hepatocellular carcinoma, amiodarone

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Authors: Taleb L., Benarbia M., Brahmi M., Belmiloud H., Boukerche A.

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Introduction and purpose of the study: Cavum cancer in children and adolescents is rare and represents 8% of all nasopharyngeal cancers treated in our department. Our objective is to study its epidemiological, clinical, therapeutic, and evolutionary particularities. Material and methods: Retrospective study of 39 patients under 20 years old, treated for undifferentiated non-metastatic carcinoma of the nasopharynx at the Emir Abdelkader Cancer Center between 2014 and 2020. Results and statistical analysis: Median age was 14 years [7-19 years], with a sex ratio of 2.9. The median time to diagnosis was 5.6 months [1 to 14 months], the circumstances of the discovery of which were dominated by lymph node syndrome in 43.6% of cases (n=17) followed by a rhinological syndrome in 30.8% of cases (n=13). The tumor stage was T1 for two patients (5.1%), T2 for 8 (20.5%), T3 for 9 (23.1%), T4 for 20 (51.3%), N0 for 2 (5 .1%) N1 for 4 (10.3%), N2 for 28 (71.8%) and N3 for 5 (12.8%). All patients received induction chemotherapy followed by concomitant radiotherapy with cisplatin. The dose of irradiation delivered to the cavum and adenopathies was 66 Gy with fractionation of 2 Gy per session in 69.2% of cases (n=27) and 1.8 Gy in 30.8% of cases (n=12). With a median follow-up of 51 months (15 to 97 months), the locoregional, metastatic, specific, and overall relapse-free survival rates at five years were 91.1%, 73.5%, 66.1%, and 68.4, respectively. Conclusion: Chemotherapy and radiotherapy treatment of cavum cancer in children and adolescents has allowed excellent locoregional control despite the advanced stage of the disease. However, the frequency of metastatic relapses could justify the possible use of systemic maintenance treatment.

Keywords: cancer, nasopharynx, radiotherapy, chemotherapy, survival

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Authors: Marcin Kruszewski, Barbara Sochanowicz, Sylwia Męczyńska-Wielgosz, Maria Wojewódzka, Lucyna Kapka-Skrzypczak

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Metallic NPs are widely used in a number of applications in industry, science and medicine. Among metallic NPs foreseen to be widely used in medicine are gold nanoparticles (AuNPs) due to their low toxicity, and silver NPs (AgNPs) due to their strong antimicrobial activity. In this study, we compared an effect of AgNPs and gold NPs (AuNPs) on the formation of DNA damage and global DNA methylation and in A2780 and 4T1 cell lines, widely used models of human ovarian carcinoma and murine mammary carcinoma, respectively. The cells were treated with AgNPs coated with citrate (AgNPs(cit) or PEG (AgNPs(PEG), or AuNPs. A global DNA methylation was investigated with ELISA, whereas the formation of DNA damage was investigated by a comet +/- FPG. AgNPs decreased global DNA methylation and increased the formation of DNA lesions in both cell lines. The effect was dependent on the type of NPs used, it's coating, and cell line used. In conclusion, the epigenetic and genotoxic effects of NPs strongly depends on NP nature and cellular context. Epigenetic changes observed upon the action of AgNPs may play a crucial role in NPs-induced changes in protein expression.

Keywords: DNA damage, gold nanoparticles, methylation, silver nanoparticles

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Authors: Sujeet Poudyal

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Introduction: Renal cell carcinoma is the most common malignancy associated with Inferior vena cava (IVC) thrombosis. Radical nephrectomy with tumor thrombectomy provides durable cancer-free survival. Other renal malignancies like Wilms’ tumors are also associated with IVC thrombus. We describe our experience with the management of renal malignancies associated with IVC thrombus. Methods: This prospective study included 28 patients undergoing surgery for renal malignancies associated with IVC thrombus from February 2017 to March 2023. Demographics of patients, types of renal malignancy, level of IVC thrombus, intraoperative details, need for venovenous bypass, cardiopulmonary bypass and postoperative outcomes were all documented. Results: Out of a total of 28 patients, 24 patients had clear cell Renal Cell Carcinoma,1 had renal osteosarcoma and 3 patients had Wilms tumor. The levels. of thrombus were II in eight, III in seven, and IV in six patients. The mean age of RCC was 62.81±10.2 years, renal osteosarcoma was 26 years and Wilms tumor was 23 years. There was a need for venovenous bypass in four patients and cardiopulmonary bypass in four patients, and the Postoperative period was uneventful in most cases except for two mortalities, one in Level III due to pneumonia and one in Level IV due to sepsis. All cases followed up till now have no local recurrence and metastasis except one case of RCC with Level IV IVC thrombus, which presented with paraaortic nodal recurrence and is currently managed with sunitinib. Conclusion: The complexity in the management of renal malignancy with IVC thrombus increases with the level of IVC thrombus. As radical nephrectomy with tumor thrombectomy provides durable cancer-free survival in most cases, the surgery should be undertaken in an expert and experienced setup with a strong cardiovascular backup to minimize morbidity and mortality associated with the procedure.

Keywords: renal malignancy, IVC thrombus, radical nephrectomy with tumor thrombectomy, renal cell carcinoma

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Authors: Vitor Rafael Regiani, Carlos Henrique Viesi Do Nascimento Filho, Patricia Matos Biselli-Chicote, Claudia Aparecida Rainho, Luiz Sergio Raposo, José Victor Maniglia, Eny Maria Goloni-Bertollo, Erika Cristina Pavarino

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Promoter hypermethylation of tumor-related genes has been associated with prognosis in early-stage head-and-neck cancers, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. Hence, we selected the MGMT and RASSF1A genes to examine the methylation status in head and neck squamous cell carcinomas (HNSCC) samples matched with non-tumor tissues (tumor-surrounding tissues or peripheral blood samples). DNA methylation analysis was based on Methylation-Sensitive High Resolution Melting, and the methylation status was correlated with clinic-pathological characteristics of the patients. RASSF1A and MGMT promoter methylation was detected in 43.24% (16/37) and in 44.44% (16/36) of the tumors, respectively. RASSF1A and MGMT methylation was significantly more frequent in tumor tissue than non-tumor tissues, as well as, simultaneous methylation of RASSF1A and MGMT also was higher in tumor tissue than non-tumor tissues. In relation to anatomic site, larynx cancer presented significant methylation of MGMT gene compared to tumor-surrounding tissue. The frequency of RASSF1A and MGMT promoter methylated was higher in tumor tissues in relation to peripheral blood from the same patient. No association was found between methylation and the variables analyzed, including gender, age, smoking or alcohol drinking habits. Clinic-pathological characteristics also showed no association in the presence of methylation. The Kaplan–Meier's method showed no association of methylation and both disease-free and overall survival. In conclusion, the presence of epigenetic abnormalities in normal-appearing tissue corroborates the hypothesis of the ‘field cancerization', or it can reflect preneoplastic and/or preinvasive. Moreover, MGMT methylation may serve as an important laryngeal cancer biomarker because it showed significant difference between laryngeal cancer and surrounding tumor tissues.

Keywords: head and neck cancer, DNA methylation, MGMT promoter methylation, RASSF1A promoter methylation

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Authors: Karl Kingsley

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Many mechanisms are involved in the control of cellular differentiation and growth, which are often dysregulated in many cancers. Many distinct pathways are involved in these mechanisms of control, including deoxyribonuclease (DNA) methyltransferase and histone deacetylase (HDAC) activation that controls both genetic and epigenetic modifications and micro ribonucleic acid (RNA) expression. Less is known about the expression of DNA methyltransferase (DNMT) and HDAC in oral cancers and the effect on microRNA expression. The primary objective of this study was to evaluate the expression of DNMT and HDAC family members in oral cancer and the concomitant expression of cancer-associated microRNAs. Using commercially available oral cancers, including squamous cell carcinoma (SCC)-4, SCC-9, SCC-15, and SCC-25, RNA was extracted and screened for DNMT, HDAC, and microRNA expression using highly-specific primers and quantitative polymerase chain reaction (qPCR). These data revealed low or absent expression of DNMT-1, which is associated with cellular differentiation but increased expression of DNMT-3a and DNMT-3b in all SCC cell lines compared with normal non-cancerous cell controls. In addition, no expression of HDAC1 and HDAC2 expression was found among the normal, non-cancerous cells but was highly expressed in each of the SCC cell lines examined. Differential expression of oncogenic and cancer-associated microRNAs was also observed among the SCC cell lines, including miR-21, miR-133, miR-149, miR-155, miR-365, and miR-720. These findings also appeared to vary according to observed growth rates among these cells. These data may be the first to demonstrate the expression and association between HDAC and DNMT3 family members among oral cancers. In addition, the differential expression of these epigenetic modifiers may be associated with the expression of specific microRNAs in these cancers, which have not previously been observed to the best of the author's knowledge. In addition, some associations and relationships may exist between the expression of these biomarkers and the rates of growth and proliferation, which may suggest that these expression patterns might represent potentially useful biomarkers to determine tumor aggressiveness and other phenotypic behaviors among oral cancers.

Keywords: oral cancer, DNA methyltransferase, histone deacetylase, microRNA

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Authors: Pelin Balcik Ercin

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Introduction: ZEB transcription factor family member ZEB2, has a role in epithelial to mesenchymal transition during development and metastasis. The altered circulating extracellular miRNAs expression is observed in diseases, and extracellular miRNAs have an important role in cancer cell microenvironment. In ChIP-Seq study, the expression of miR-2110 was found to be regulated by ZEB2. In this study, the effects of miR2110 on cell proliferation and migration of hepatocellular carcinoma (HCC) cells were examined. Material and Methods: SNU398 cells transfected with mimic miR2110 (20nM) (HMI0375, Sigma-Aldrich) and negative control miR (HMC0002, Sigma-Aldrich). MicroRNA isolation was accomplished with miRVANA isolation kit according to manufacturer instructions. cDNA synthesis was performed expression, respectively, and calibrated with Ct of controls. The real-time quantitative PCR (RT-qPCR) reaction was performed using the TaqMan Fast Advanced Master Mix (Thermo Sci.). Ct values of miR2110 were normalized to miR-186-5p and miR16-5p for the intracellular gene. Cell proliferation analysis was analyzed with the xCELLigence RTCA System. Wound healing assay was analyzed with the ImageJ program and relative fold change calculated. Results: The mimic-miR-2110 transfected SNU398 cells nearly nine-fold (log2) more miR-2110 expressed compared to negative control transfected cells. The mimic-miR-2110 transfected HCC cell proliferation significantly inhibited compared to the negative control cells. Furthermore, miR-2110-SNU398 cell migration capacity was relatively four-fold decreased compared to negative control-miR-SNU398 cells. Conclusion: Our results suggest the miR-2110 inhibited cell proliferation and also miR-2110 negatively affect cell migration compared to control groups in HCC cells. These data suggest the complexity of microRNA EMT transcription factors regulation. These initial results are pointed out the predictive biomarker capacity of miR-2110 in HCC.

Keywords: epithelial to mesenchymal transition, EMT, hepatocellular carcinoma cells, micro-RNA-2110, ZEB2

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Authors: Lucie Matricon, Anne Roubaud, Geert Haarlemmer, Christophe Geantet

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Introduction: This case discusses the management of two floor of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. Case Report: A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Discussion: Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk, and second primary cancer development.

Keywords: microalgae, biofuels, hydrothermal liquefaction, biomass

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Authors: Shu-Jun Li, Cheng-Cao Sun, De-Jia Li

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Recently, long noncoding RNAs (lncRNAs) have been emerged as crucial regulators of human diseases and prognostic markers in numerous of cancers, including colorectal carcinoma (CRC). Here, we identified an oncogenetic lncRNA HULC, which may promote colorectal tumorigenesis. HULC has been found to be up-regulated and acts as oncogene in gastric cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in CRC is still undetermined. Here, we reported that HULC expression is also over-expressed in CRC, and its increased level is associated with poor prognosis and shorter survival. Knockdown of HULC impaired CRC cells proliferation, migration and invasion, facilitated cell apoptosis in vitro, and inhibited tumorigenicity of CRC cells in vivo. Mechanistically, RNA immunoprecipitation (RIP) and RNA pull-down experiment demonstrated that HULC could simultaneously interact with EZH2 to repress underlying targets NKD2 transcription. In addition, rescue experiments determined that HULC oncogenic function is partly dependent on repressing NKD2. Taken together, our findings expound how HULC over-expression endows an oncogenic function in CRC.

Keywords: long noncoding RNA, HULC, NKD2, colorectal carcinoma, proliferation, apoptosis

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Authors: Tery Nehemia Nugraha Joseph, J. D. P. Wisnubroto

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Thyroid cancer is a healthcare problem with high morbidity and mortality. Follicular adenoma and follicular carcinoma are thyroid tumors from the thyroid follicular cells differentiation with a microfollicular pattern that consists of follicular cuboidal cells. vascular endothelial growth factor (VEGF) is a potent and powerful mitogen for endothelial cells and increases vascular permeability. Therefore, due to an increase in thyroid-stimulating hormone (TSH), VEGF production is activated in the thyroid that leads to the end of mitogenic TSH stimulation and initiation of angiogenesis. The differences in VEGF levels in the follicular carcinoma of thyroid tissue with follicular adenoma thyroid can be used as a basis in differentiating the two types of neoplasms. This study aims to analyze VEGF in the serum so that it can be used to differentiate the types of thyroid carcinoma before surgery. This study uses a cross-sectional research design. Samples were carried out by taking serum samples, and the VEGF levels were calculated. Data were analyzed using the Mann-Whitney test. The results found a significant difference between VEGF levels in the follicular carcinoma thyroid group and VEGF levels in the follicular adenoma thyroid group with a value of p = 0.007 (p < 0.05). The results obtained are 560,427 ± 160,506 ng/mL in the type of follicular carcinoma thyroid and 320.943 ± 134.573 ng/mL in the type of follicular adenoma thyroid. VEGF levels between follicular adenoma and follicular carcinoma are different. VEGF levels are higher in follicular carcinoma thyroid than follicular adenoma thyroid.

Keywords: follicular adenoma thyroid, follicular carcinoma thyroid, thyroid, VEGF

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Authors: Maha Soltan, Amal Z. Hassan, Howaida I. Abd-Alla, Atef G. Hanna

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Two naturally known cardenolides; acovenoside A and acobioside A were isolated from the Egyptian cultivar; Acokanthera spectabilis leaves. It is an ornamental and poisonous plant that has been traditionally claimed for their medicinal properties against infectious microbes, killing worms and curing some inflammations at little amounts. We examined the growth inhibition effects of both cardenolides against four types of human cancer cell lines using Sulphorhodamine B assay. In addition, the clonogenic assay was also performed for testing the growth inhibiting power of the isolated compounds. An in vitro mechanistic investigation was further accomplished against hepatocellular carcinoma HepG2 cell line. Microscopic examination, colorimetric ELISA and flow cytometry techniques were our tools of proving at least part of the anticancer pathway of the tested compounds. Both compounds were able to inhibit the growth of 4 human cancer cell lines at less than 100 nM. In addition, they were able to activate the executioner Caspase-3 and apoptosis was then induced as a consequence of cell growth arrest at G2/M. An attention must be payed to those bioactive agents particularly when giving their activity against cancer cells at considerable small values while presenting safe therapeutic margins as indicated by literature.

Keywords: anticancer, cardenolides, Caspase-3, apoptosis

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Authors: Moizza Tahir, Uzma Bashir, Aisha Akhtar, Zainab Ansari, Sameen Ansari, Muhammad Ali Tahir

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Cancer burden has globally increased. Among cutaneous cancers basal cell carcinoma constitute vast majority of skin cancer. There is need for appropriate diagnostic, therapeutic and prognostic significance evaluation for skin cancers Present study report intraoperative frozen section (FS) histopathological clearance for excision of BCC in a tertiary care center and find the frequency of involvement of surgical margin with reference to anatomical site, with size and surgical technique. It was prospective open label interventional study conducted at Dermatology department of tertiary care hospital Rawalpindi Pakistan in lais on with histopathology department from January 2023 to April 2024. Total of thirty-six (n = 36) patients between age 45-80 years with basal cell carcinoma of 10-20mm on face were included following inclusion exclusion criteria by purposive sampling technique. Informed consent was taken. Surgical excision was performed and intraoperative frozen section histopathology clearance of tumor margin was taken from histopathologist on telephone. Surgical reconstruction was done. Final Histopathology report was reexamined on day 10th for margin and depth clearance. Descriptive statistics were calculated for age, gender, sun exposure, reconstructive technique, anatomical site, and tumor free margin report on frozen section analysis. Chi square test was employed for statistical significance of involvement of surgical margin with reference to anatomical site, size and decision on reconstructive surgical technique, p value of <0.05 was considered significant. Total of 36 patients of BCC were enrolled, males 12 (33.3%) and females were 24 (66.6%). Age ranged from 45 year to 80 year mean of 58.36 ±SD7.8. Size of BCC ranged from 10mm to 35mm mean of 25mm ±SD 0.63. Morphology was nodular 18 (50%), superficial spreading 11(30.6%), morphoeic 1 (2.8%) and ulcerative in 6(16.7%) cases. Intraoperative frozen section for histopathological margin clearance with 2-3 mm safety margin and surgical technique has p-value0.51, for anatomical site p value 0.24 and size p-0.84. Intraoperative frozen section (FS) histopathological clearance for BCC face with 2-3mm safety margin with reference to reconstructive technique, anatomical site and size of BCC were insignificant.

Keywords: basal cell carcinoma, tumor free amrgin, basal cell carcinoma and frozen section, safety margin

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Authors: P. Annapurna, Cecil Ross, Sudhir Krishna, Sweta Srivastava

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Irradiation plays a pivotal role in cervical cancer treatment, however some tumors exhibit resistance to therapy while some exhibit relapse, due to better repair and enhanced resistance mechanisms operational in their cells. The present study aims to understand the signaling mechanism operational in resistance phenotype and in the present study we report the role of Rho GTPase associated protein kinase (ROCK) signaling in cervical carcinoma radio-resistance. ROCK signaling has been implicated in several tumor progressions and is important for DNA repair. Irradiation of spheroid cultures of SiHa cervical carcinoma derived cell line at 6Gy resulted in generation of resistant cells in vitro which had better clonogenic abilities and formed larger and more colonies, in soft agar colony formation assay, as compared to the non-irradiated cells. These cells also exhibited an enhanced motility phenotype. Cell cycle profiling showed the cells to be blocked in G2M phase with enhanced pCDC2 levels indicating onset of possible DNA repair mechanism. Notably, 3 days post-irradiation, irradiated cells showed increased ROCK2 translocation to the nucleus with enhanced protein expression as compared to the non-irradiated cells. Radio-sensitization of the resistant cells was enhanced using Y27632, an inhibitor to ROCK signaling. The treatment of resistant cells with Y27632 resulted in increased cell death upon further irradiation. This observation has been confirmed using inhibitory antibodies to ROCK1/2. Result show that both ROCK1/2 have a functional contribution in radiation resistance of cervical cancer cells derived from cell lines. Interestingly enrichment of stem like cells (Hoechst negative cells) was also observed upon irradiation and these cells were markedly sensitive to Y27632 treatment. Our results thus suggest the role of ROCK signaling in radio-resistance in cervical carcinoma. Further studies with human biopsies, mice models and mechanistic of ROCK signaling in the context of radio-resistance will clarify the role of this molecule further and allow for therapeutics development.

Keywords: cervical carcinoma, radio-resistance, ROCK signaling, cancer treatment

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Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been verified as an oncogenic gene in several human malignant tumors, and its dysregulation was closed associated with tumor initiation, development and progression. Nevertheless, whether the aberrant expression of XIST in human nasopharyngeal carcinoma (NPC) is corrected with malignancy, metastasis or prognosis has not been elaborated. Here, we discovered that XIST was up-regulated in NPC tissues and higher expression of XIST contributed to a markedly poorer survival time. In addition, multivariate analysis demonstrated XIST was an independent risk factor for prognosis. XIST over-expression enhanced, while XIST silencing hampered the cell growth in NPC. Additionally, mechanistic analysis revealed that XIST up-regulated the expression of miR-34a-5p targeted gene E2F3 through acting as a competitive ‘sponge’ of miR-34a-5p. Taking all into account, we concluded that XIST functioned as an oncogene in NPC through up-regulating E2F3 in part through ‘spongeing’ miR-34a-5p.

Keywords: X inactivate-specific transcript; hsa-miRNA-34a-5p, miR-34a-5p; E2F3, nasopharyngeal carcinoma, tumorigenesis

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Authors: Yao Song, Danni Cheng, Jianjun Ren

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Objectives: We aimed to explore the prognostic effects of absolute values and dynamic changes of common hematological indices on oropharynx squamous cell carcinoma (OPSCC) patients treated with radiation. Methods and materials: The absolute values of white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), hemoglobin (Hb), platelet (Plt), albumin (Alb), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline (within 45 days before radiation), 1-, 3-, 6- and 12-months after the start of radiotherapy were retrospectively collected. Locally-estimated smoothing scatterplots were used to describe the smooth trajectory of each index. A mixed-effect model with a random slope was fitted to describe the changing rate and trend of indices over time. Cox proportional hazard analysis was conducted to assess the correlation between hematological indices and treatment outcomes. Results: Of the enrolled 85 OPSCC patients, inflammatory indices, such as WBC and ALC, dropped rapidly during acute treatment and gradually recovered, while NLR and PLR increased at first three months and subsequently declined within 3-12 months. Higher absolute value or increasing trend of nutritional indices (Alb and Hb) was associated with better prognosis (all p<0.05). In contrast, patients with higher absolute value or upward trend of inflammatory indices (WBC, ANC, Plt, PLR and NLR) had worse survival (all p<0.05). Conclusions: The absolute values and dynamic changes of hematological indices were valuable prognostic factors for OPSCC patients who underwent radiotherapy.

Keywords: hematological indices, oropharyngeal cancer, radiotherapy, NLR, PLR

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Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here, we report the definition of miR-346 as an oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.

Keywords: microRNA-346, miR-346, XPC, non-small cell lung cancer, oncogenesis

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Authors: Bliss Singhal

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Machine learning (ML) is a branch of Artificial Intelligence (AI) where computers analyze data and find patterns in the data. The study focuses on the detection of metastatic cancer using ML. Metastatic cancer is the stage where cancer has spread to other parts of the body and is the cause of approximately 90% of cancer-related deaths. Normally, pathologists spend hours each day to manually classifying whether tumors are benign or malignant. This tedious task contributes to mislabeling metastasis being over 60% of the time and emphasizes the importance of being aware of human error and other inefficiencies. ML is a good candidate to improve the correct identification of metastatic cancer, saving thousands of lives and can also improve the speed and efficiency of the process, thereby taking fewer resources and time. So far, the deep learning methodology of AI has been used in research to detect cancer. This study is a novel approach to determining the potential of using preprocessing algorithms combined with classification algorithms in detecting metastatic cancer. The study used two preprocessing algorithms: principal component analysis (PCA) and the genetic algorithm, to reduce the dimensionality of the dataset and then used three classification algorithms: logistic regression, decision tree classifier, and k-nearest neighbors to detect metastatic cancer in the pathology scans. The highest accuracy of 71.14% was produced by the ML pipeline comprising of PCA, the genetic algorithm, and the k-nearest neighbor algorithm, suggesting that preprocessing and classification algorithms have great potential for detecting metastatic cancer.

Keywords: breast cancer, principal component analysis, genetic algorithm, k-nearest neighbors, decision tree classifier, logistic regression

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Authors: H. M. El-Rafie, A. H. Abou Zeid, R. S. Mohammed, A. A. Sleem

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Acrocarpus is a genus of flowering plants in the legume family Fabaceae which considered as a large and economically important family. This study aimed to investigate the phytoconstituents of the petroleum ether extract (PEE) of Acrocarpus fraxinofolius bark by Gas chromatography coupled with mass spectrometry (GC/MS) analysis of its fractions (fatty acid and unsaponifiable matter). Concerning this, identification of 52 compounds constituting 97.03 % of the total composition of the unsaponifiable matter fraction. Cycloeucalenol was found to be the major compound representing 32.52% followed by 4a, 14a-dimethyl-A8~24(28)-ergostadien (26.50%) and ß-sitosterol(13.74%), furthermore Gas liquid chromatography (GLC) analysis of the sterol fraction revealed the identification of cholesterol (7.22 %), campesterol (13.30 %), stigmasterol (10.00 %) and β - sitosterol (69.48 %). Meanwhile, the identification of 33 fatty acids representing 90.71% of the total fatty acid constituents. Methyl-9,12-octadecadienoate (40.39%) followed by methyl hexadecanoate (23.64%) were found to be the major compounds. On the other hand, column chromatography and Thin layer chromatography (TLC) fractionation of PEE separate the triterpenoid: 21β-hydroxylup-20(29)-en-3-one and β- amyrin which were structurally identified by spectroscopic analysis (NMR, MS and IR). PEE has been biologically evaluated for 1: management of diabetes in alloxan induced diabetic rats 2: cytotoxic activity against four human tumor cell lines (Cervix carcinoma cell line[HELA], Breast carcinoma cell line [MCF7], Liver carcinoma cell line[HEPG2] and Colon carcinoma cell line[HCT-116] 3: hepatoprotective activity against CCl4-induced hepatotoxicity in rats and the activity was studied by assaying the serum marker enzymes like AST, ALT, and ALP. Concerning this, the anti-diabetic activity exhibited by 100mg of PEE extract was 74.38% relative to metformin (100% potency). It also showed a significant anti-proliferative activity against MCF-7 (IC50= 2.35µg), Hela(IC50=3.85µg) and HEPG-2 (IC50= 9.54µg) compared with Doxorubicin as reference drug. The hepatoprotective activity was evidenced by significant decrease in liver function enzymes, i.e. AST, ALT and ALP by (29.18%, 28.26%, and 34.11%, respectively using silymarin as the reference drug, compared to their concentration levels in an untreated group with liver damage induced by CCl₄. This study was performed for the first time on the bark of this species.

Keywords: Acrocarpus fraxinofolius, antidiabetic, cytotoxic, hepatoprotective

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Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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Authors: Danni Cheng

Abstract:

Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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Authors: Roland Benedict Reyes, Marc Edsel Ayes, Regina Berba, Cybele Lara Abad

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Background: Three AIDS-defining malignancies have been associated with the human immunodeficiency virus (HIV): Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical carcinoma. However, new cases of non-AIDS defining malignancies also have been increasingly associated with HIV. One of these is a rare intracranial malignancy, meningeal hemangiopericyotma. Case Description: A 32-year old HIV-positive male, not on highly active antiretroviral therapy, was admitted to our hospital due to generalized weakness and sudden onset hearing loss. Cranial MRI was done, which revealed a temporal nodule with the following considerations: granuloma, meningioma or metastases. A craniotomy was performed and the mass excised. Results from the biopsy showed meningeal hemangiopericytoma. The patient was then started on antiretroviral therapy (Lamivudine, Tenofovir, and Efavirenz) and was discharged for radiation therapy and metastatic work-up as an outpatient. On follow-up seven months later, metastatic work up revealed multiple hepatic foci not previously documented suggestive of metastasis short of biopsy sampling. Conclusions: This case of an intracranial hemangiopericytoma in an HIV-positive patient is the second case thus far presented, based on our systematic and extensive search of the literature.

Keywords: Hemangiopericytoma, Human Immunodeficiency Virus, Meningeal hemangiopericytoma, Neoplasm

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Authors: Joseph M. Rich, Vinay A. Duddalwar, Assad A. Oberai

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Prostate adenocarcinoma is the most common cancer in males, with osseous metastases as the commonest site of metastatic prostate carcinoma (mPC). Treatment monitoring is based on the evaluation and characterization of lesions on multiple imaging studies, including Computed Tomography (CT). Monitoring of the osseous disease burden, including follow-up of lesions and identification and characterization of new lesions, is a laborious task for radiologists. Deep learning algorithms are increasingly used to perform tasks such as identification and segmentation for osseous metastatic disease and provide accurate information regarding metastatic burden. Here, nnUNet was used to produce a model which can segment CT scan images of prostate adenocarcinoma vertebral bone metastatic lesions. nnUNet is an open-source Python package that adds optimizations to deep learning-based UNet architecture but has not been extensively combined with transfer learning techniques due to the absence of a readily available functionality of this method. The IRB-approved study data set includes imaging studies from patients with mPC who were enrolled in clinical trials at the University of Southern California (USC) Health Science Campus and Los Angeles County (LAC)/USC medical center. Manual segmentation of metastatic lesions was completed by an expert radiologist Dr. Vinay Duddalwar (20+ years in radiology and oncologic imaging), to serve as ground truths for the automated segmentation. Despite nnUNet’s success on some medical segmentation tasks, it only produced an average Dice Similarity Coefficient (DSC) of 0.31 on the USC dataset. DSC results fell in a bimodal distribution, with most scores falling either over 0.66 (reasonably accurate) or at 0 (no lesion detected). Applying more aggressive data augmentation techniques dropped the DSC to 0.15, and reducing the number of epochs reduced the DSC to below 0.1. Datasets have been identified for transfer learning, which involve balancing between size and similarity of the dataset. Identified datasets include the Pancreas data from the Medical Segmentation Decathlon, Pelvic Reference Data, and CT volumes with multiple organ segmentations (CT-ORG). Some of the challenges of producing an accurate model from the USC dataset include small dataset size (115 images), 2D data (as nnUNet generally performs better on 3D data), and the limited amount of public data capturing annotated CT images of bone lesions. Optimizations and improvements will be made by applying transfer learning and generative methods, including incorporating generative adversarial networks and diffusion models in order to augment the dataset. Performance with different libraries, including MONAI and custom architectures with Pytorch, will be compared. In the future, molecular correlations will be tracked with radiologic features for the purpose of multimodal composite biomarker identification. Once validated, these models will be incorporated into evaluation workflows to optimize radiologist evaluation. Our work demonstrates the challenges of applying automated image segmentation to small medical datasets and lays a foundation for techniques to improve performance. As machine learning models become increasingly incorporated into the workflow of radiologists, these findings will help improve the speed and accuracy of vertebral metastatic lesions detection.

Keywords: deep learning, image segmentation, medicine, nnUNet, prostate carcinoma, radiomics

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Authors: Abdul Matin, Muhammad Ajmal, Uzma Yunus, Noaman-ul Haq, Hafiz M. Shohaib, Ambreen G. Muazzam

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Carbon nanoparticles (CNPs) have unique properties that are useful for the diagnosis and treatment of cancer due to their precise properties like small size (ideal for delivery within the body) stability in solvent and tunable surface chemistry for targeted delivery. Here, highly fluorescent, monodispersed and water-soluble CNPs were synthesized directly from a suitable carbohydrate source (glucose and sucrose) by one-step acid assisted ultrasonic treatment at 35 KHz for 4 hours. This method is green, simple, rapid and economical and can be used for large scale production and applications. The average particle sizes of CNPs are less than 10nm and they emit bright and colorful green-blue fluorescence under the irradiation of UV-light at 365nm. The CNPs were characterized by scanning electron microscopy, fluorescent spectrophotometry, Fourier transform infrared spectrophotometry, ultraviolet-visible spectrophotometry and TGA analysis. Fluorescent CNPs were used as fluorescent probe and nano-carriers for anticancer drug. Functionalized CNPs (with ethylene diamine) were attached with anticancer drug-Methotrexate. In vitro bioactivity and biocompatibility of CNPs-drug conjugates was evaluated by LDH assay and Sulforhodamine B assay using human lung carcinoma cell lines (H157). Our results reveled that CNPs showed biocompatibility and CNPs-anticancer drug conjugates have shown potent cytotoxic effects and high antitumor activities in lung cancer cell lines. CNPs are proved to be excellent substitute for conventional drug delivery cargo systems and anticancer therapeutics in vitro. Our future studies will be more focused on using the same nanoparticles in vivo model system.

Keywords: carbon nanoparticles, carbon nanoparticles-methotrexate conjugates, human lung carcinoma cell lines, lactate dehydrogenase, methotrexate

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Authors: Zahra Sokar, Sara Oufquir, Brahim Eddafali, Abderrahman Chait

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Fenugreek is one of the oldest plants used in traditional herbal medicine. Several studies have demonstrated the anticancer effects of seeds by inhibiting the proliferation, angiogenesis, invasion and metastasis of various cancers. While there is plenty of research demonstrating the antineoplastic effects of dormant seeds, little is known about the potential of sprouts in fighting cancer. Therefore, we propose to study the chemoprotective effect of germinating fenugreek seeds on keratoacanthoma skin cancer induced by cutaneous exposure to DMA/Croton oil in mice. The results obtained show that oral administration of 250 and 500 mg/kg aqueous sprout seed extract reduces the incidence, rate, volume, and tumor weight in a very significant manner. Histological examination revealed that mice treated with 250 mg/kg showed strong inhibition of squamous cell carcinoma formation with thickening of the epithelial layer and mild acanthosis and hyperkeratosis. A dose of 500 mg/kg prevented invasion and the occurrence of hyperkeratosis. Fenugreek sprouts appear to be a promising natural product for preventing keratoacanthoma skin cancer. Nevertheless, further studies in the same field need to be developed to evaluate the antineoplastic potential of germinated seeds.

Keywords: anticancer, fenugreek, keratoacanthoma, sprouts

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Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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