Figure 4 - uploaded by Richard C K Jordan
Content may be subject to copyright.
Poorly differentiated squamous cell carcinoma of tonsil with no evidence of keratinisation (A). Polymerase chain reaction products of DNA extracted from formalin fixed, paraffin embedded tissue show the presence of HPV-16 DNA in lanes 3 to 5 (B). Strong immunoexpression of p16 in same cases (C) with markedly reduced expression of Rb protein (D).
Source publication
Squamous cell carcinoma of the head and neck (HNSCC) is a heterogeneous but largely preventable disease with complex molecular abnormalities. It arises from a premalignant progenitor followed by outgrowth of clonal populations associated with cumulative genetic alterations and phenotypic progression to invasive malignancy. These genetic alterations...
Context in source publication
Context 1
... In accordance with the oncogenic properties of E6, approximately 90% of HPV-HNSCCs have wild type p53 and lack immunohistochemical overexpression of p53. 80 92 98 99 Given the ability of E7 to target Rb for degradation, Rb expression is decreased in HPV-HNSCC (fig 4). 92 100 Absence of p16 mutations and overexpression of p16 INK4A are also molecular hallmarks of HPV-HNSCC. ...
Citations
... Thus, distinguishing these histological subtypes from ordinary OSCCs is critical. 4 Acantholytic squamous cell carcinoma is an unusual, histologically distinct type of SCC that was initially described by Lever in 1947 and affects sun-exposed skin. 5 ASCC has a cumulative incidence of 0.1%. ...
Background
Acantholytic squamous cell carcinoma (ASCC) is an uncommon histological variation of oral squamous cell carcinoma (OSCC), accounting for fewer than 4% of all occurrences. The tumor shows a slight masculine predisposition, with the lower lip being the most commonly affected location. ASCC is reported to have a diverse biologic behavior, which explains its ability to metastasize to distant places and, thus, its poor prognosis. Similarly, clear cell change in OSCC is a rare occurrence with an unknown etiology that suggests its aggressive nature.
Method and Results
Histopathology reveals central acantholytic cells with numerous duct-like features. The presence of distinct cytological atypia contributes to the diagnosis of SCC. Special stains and IHC aid in distinguishing tumor from other histopathologically similar entities.
Conclusion
The case of a 29-year-old male presented here with an updated literature review highlights the need for histological study of the unique and seldom seen oral ASCC with clear cell change, which can be ignored because of similarities with other entities. Because recurrence rates are so high for ASCC, amalgamated clear cell change makes it critical for proper treatment initiation with a definite diagnosis. To the best of our knowledge, this is the first documented occurrence. Our experience with the present case suspected a more aggressive behavior due to a high Ki-67 index, anticipating a poorer prognosis in the oral cavity considering the patient's young age.
Keywords:
Oral Squamous Cell Carcinoma; Acantholytic Squamous Cell Carcinoma; Clear Cells; immunohistochemistry
... It is widely assumed that SCC arises from a premalignant progenitor, followed by the outgrowth of clonal cells with cumulative genetic alterations and phenotypic changes that lead to invasive malignancy [53]. For all cancer variants, frequent genetic alterations occur, such as inactivation of tumor suppressor genes and activation of proto-oncogenes through deletions, point mutations, promoter methylation, and gene amplification [54]. These are the main mechanisms of carcinogenesis. ...
... The incidence of p16/HPV positivity in LSCC is generally low and varies geographically [56]. However, p16 expression is more commonly observed in non-smokers [54], females [57], and younger patients [58] with LSCC. Both p16 and p14ARF are involved in regulating the G1 cell cycle and mediating the degradation of p53 by MDM2. ...
Laryngeal cancer is a very common tumor in the upper aero-digestive tract. Understanding its biological mechanisms has garnered significant interest in recent years. The development of laryngeal squamous cell carcinoma (LSCC) follows a multistep process starting from precursor lesions in the epithelium. Various risk factors have been associated with laryngeal tumors, including smoking, alcohol consumption, opium use, as well as infections with HPV and EBV viruses, among others. Cancer development involves multiple steps, and genetic alterations play a crucial role. Tumor suppressor genes can be inactivated, and proto-oncogenes may become activated through mechanisms like deletions, point mutations, promoter methylation, and gene amplification. Epigenetic modifications, driven by miRNAs, have been proven to contribute to LSCC development. Despite advances in molecular medicine, there are still aspects of laryngeal cancer that remain poorly understood, and the underlying biological mechanisms have not been fully elucidated. In this narrative review, we examined the literature to analyze and summarize the main steps of carcinogenesis and the risk factors associated with laryngeal cancer.
... The most representative evidence for the importance of loss of pRb function in tumor initiation comes from the genetic study of members of families in which an alteration in RB gene alleles is inherited that predisposes to the development of familial retinoblastoma [6][7][8]. It has also been shown in cervical and oropharyngeal cancer, closely associated with HPV infection, that these viruses inactivate pRb through its E7 oncoprotein, this being the mechanism of oncogenic initiation [9,10], and similar findings have been documented for virus-induced hepatocarcinoma [11]. These tumor-initiating actions linked to RB loss occur both in stem cells-in which normofunctioning RB keeps them in a quiescent state, their usual situation-and in postmitotic differentiated cells-in which RB mutation allows them to reintegrate into the cell cycle-and, especially in proliferative progenitor cells (called transitory amplifying cells in the oral epithelium), which constitute an intermediate step between stem cells and postmitotic differentiated cells. ...
... These tumor-initiating actions linked to RB loss occur both in stem cells-in which normofunctioning RB keeps them in a quiescent state, their usual situation-and in postmitotic differentiated cells-in which RB mutation allows them to reintegrate into the cell cycle-and, especially in proliferative progenitor cells (called transitory amplifying cells in the oral epithelium), which constitute an intermediate step between stem cells and postmitotic differentiated cells. It seems likely that transient amplifying cells are the essential source of malignant and premalignant clones in the oral epithelium [12], where loss of pRb could maintain proliferation by preventing their cell cycle exit in G1, which occurs physiologically in these cells after the development of several proliferative cycles [9][10][11][12][13]. ...
This systematic review and meta-analysis aims to evaluate the scientific evidence on the implications of retinoblastoma protein (pRb) alterations in oral cancer, in order to determine its prognostic and clinicopathological significance. PubMed, Embase, Web of Science, and Scopus were searched for studies published before February 2022, with no restrictions by publication date or language. The quality of the studies using the Quality in Prognosis Studies tool (QUIPS tool). Meta-analysis was conducted to achieve the proposed objectives, as well as heterogeneity, subgroup, meta-regression, and small study-effects analyses. Twenty studies that met the inclusion criteria (2451 patients) were systematically reviewed and meta-analyzed. Our results were significant for the association between the loss of pRb expression and a better overall survival (HR = 0.79, 95%CI = 0.64–0.98, p = 0.03), whereas no significant results were found for disease-free survival or clinico-pathological parameters (T/N status, clinical stage, histological grade). In conclusion, our evidence-based results demonstrate that loss of pRb function is a factor associated with improved survival in patients with OSCC. Research lines that should be developed in the future are highlighted.
... The pRb protein achieves this function by sequestering the E2F transcription factors and thus keeps them away from their target genes. Alterations in the RB tumor suppressor gene are important in tumor initiation and early progression of neoplasms, as has been demonstrated in members of families that inherit alterations in RB alleles that predispose them to the development of familial retinoblastoma [97][98][99], as well as in carcinomas of the uterine cervix and oropharynx, in which HPV viruses, via their E7 oncoprotein, inactivate pRb [100,101]. There is no secondary-level evidence (systematic reviews and meta-analyses) on RB alterations in OLP, and there is only one primary-level study that showed that a loss of RB function was very rare in OLP [102]. ...
Oral lichen planus (OLP) is a common chronic inflammatory disease of unknown etiology and likely autoimmune nature that is currently considered an oral potentially malignant disorder, implying that patients suffering from this process are at risk of developing oral cancer in their lifetime. The molecular alterations that develop in OLP and that make the affected oral epithelium predisposed to malignancy are unknown, although, as in other autoimmune diseases (ulcerative colitis, primary biliary cirrhosis, etc.), they may be linked to oncogenesis-promoting effects mediated by the inflammatory infiltrate. So far there is no in-depth knowledge on how these hallmarks of cancer are established in the cells of the oral epithelium affected by OLP. In this scoping review of systematic reviews and meta-analyses the state of evidence based knowledge in this field is presented, to point out gaps of evidence and to indicate future lines of research. MEDLINE, Embase, Cochrane Library and Dare were searched for secondary-level studies published before October 2022. The results identified 20 systematic reviews and meta-analyses critically appraising the hallmarks tumor-promoting inflammation (n = 17, 85%), sustaining proliferative signaling (n = 2, 10%), and evading growth suppressors (n = 1, 5%). No evidence was found for the other hallmarks of cancer in OLP. In conclusion, OLP malignization hypothetically derives from the aggressions of the inflammatory infiltrate and a particular type of epithelial response based on increased epithelial proliferation, evasion of growth-suppressive signals and lack of apoptosis. Future evidence-based research is required to support this hypothesis.
... Patients with HPV-positive carcinomas are likely to be younger, nonsmokers, have early lymph node metastasis, and have a social history of more frequent heterosexual and orogenital sexual contacts. Oropharyngeal, in particular tonsillar, carcinomas have the highest rates of HPV DNA detection ranging from 45% to 67% of those studied compared with oral cavity lesion whereas HPV DNA has been found in 12% to 18% [9][10][11]. ...
Oral cancer considered one of the most 10 cancer among world population [1]. In the period between 1995- 2015 Saudi cancers registries detect 172,424 cancer cases, 3184 were oral cancer cases. 1.5 Per 100000 for female population and 1.4 per 100000 among male population, the majority of cases are from jazan region [2, 3]. The aim of this review is to explain the basic and essential aspects of oral cancer focusing on squamous cell carcinoma , starting from its definition to epidemiology in Saudi Arabia as well world wild as well addressing carcinogenesis , potential malignant diseases , and premalignant lesions. As oral cancer is preventable disease, prevention will be addressed as well.
... The most representative evidence for the importance of loss of RB function in tumour initiation comes from the genetic study of members of families in which an alteration in the alleles of the RB gene predisposing to the development of familial retinoblastoma is inherited [147][148][149]. It has also been shown in cervical and oropharyngeal cancer, closely associated with HPV infection, that these viruses inactivate pRb through their E7 oncoprotein, this being the mechanism of oncogenic initiation [150,151], and similar findings have been documented for virus-induced hepatocarcinoma [152]. These tumour-initiating actions linked to the loss of RB occur both in stem cells-in which normofunctioning RB keeps them in a quiescent state, their usual situation-and in post-mitotic differentiated cells-in which the RB mutation allows them to reintegrate into the cell cycle-and, above all, in proliferative progenitor cells (called transient amplifying cells in the oral epithelium), which constitute an intermediate step between stem cells and post-mitotic differentiated cells. ...
... These tumour-initiating actions linked to the loss of RB occur both in stem cells-in which normofunctioning RB keeps them in a quiescent state, their usual situation-and in post-mitotic differentiated cells-in which the RB mutation allows them to reintegrate into the cell cycle-and, above all, in proliferative progenitor cells (called transient amplifying cells in the oral epithelium), which constitute an intermediate step between stem cells and post-mitotic differentiated cells. It seems likely that transient amplifying cells are the essential source of malignant and premalignant clones in the oral epithelium [153] where the loss of RB could maintain proliferation by preventing their exit from the cell cycle in G1, which occurs physiologically in these cells after the development of several proliferative cycles [150][151][152][153][154]. ...
... Sedghizadeh et al. [71] reported in their meta-analysis of 18 studies that p16 overexpression improved the survival of patients with oropharyngeal carcinoma 2.77-fold, which is to be expected as p16 is essentially overexpressed in HPV+ cases, which are known to behave in a more benign manner. Oropharyngeal carcinomas are currently considered a different disease from oral cavity cancer, more frequently associated with HPV-positive infection, also showing discrepancies regarding their biology [4,150]. Oropharyngeal HPV-positive tumours frequently harbour a downregulation of TP53/p53 (due to inactivation and degradation by the major viral oncoprotein E6), and exhibit increased p16 expression (due to the suppression of retinoblastoma protein [pRb] by E7, with cell cycle arrest and p16 accumulation) [4,150]. ...
In 2000 and 2011, Hanahan and Weinberg published two papers in which they defined the characteristics that cells must fulfil in order to be considered neoplastic cells in all types of tumours that affect humans, which the authors called “hallmarks of cancer”. These papers have represented a milestone in our understanding of the biology of many types of cancers and have made it possible to reach high levels of scientific evidence in relation to the prognostic impact that these hallmarks have on different tumour types. However, to date, there is no study that globally analyses evidence-based knowledge on the importance of these hallmarks in oral and oropharyngeal squamous cell carcinomas. For this reason, we set out to conduct this scoping review of systematic reviews with the aim of detecting evidence gaps in relation to the relevance of the cancer hallmarks proposed by Hanahan and Weinberg in oral and oropharyngeal cancer, and oral potentially malignant disorders, and to point out future lines of research in this field.
... Every cell contains numerous more basic components named subcellular compartments or subcellular organelles (Reece, 2015). According to the presence or absence of membranes, these subcellular organelles can be divided into two categories, the membrane bounded subcellular compartments and the non-membrane bounded subcellular structures (Perez-Ordonez et al., 2006). The membrane bounded subcellular compartments are those compartments surrounded by a single or double lipid layer membrane, such as mitochondria, nucleus and chloroplasts (in photosynthetic organisms). ...
Eukaryotic cells contain numerous components, which are known as subcellular compartments or subcellular organelles. Proteins must be sorted to proper subcellular compartments to carry out their molecular functions. Mis-localized proteins are related to various cancers. Identifying mis-localized proteins is important in understanding the pathology of cancers and in developing therapies. However, experimental methods, which are used to determine protein subcellular locations, are always costly and time-consuming. We tried to identify cancer-related mis-localized proteins in three different cancers using computational approaches. By integrating gene expression profiles and dynamic protein-protein interaction networks, we established DPPN-SVM (Dynamic Protein-Protein Network with Support Vector Machine), a predictive model using the SVM classifier with diffusion kernels. With this predictive model, we identified a number of mis-localized proteins. Since we introduced the dynamic protein-protein network, which has never been considered in existing works, our model is capable of identifying more mis-localized proteins than existing studies. As far as we know, this is the first study to incorporate dynamic protein-protein interaction network in identifying mis-localized proteins in cancers.
... Inversely, administration of the FD extract at high dose in both the chemopreventive and chemotherapeutic groups decreased the cyclin D1 expression which was restricted to the basal compartment of the keratinised stratified squamous epithelium. is could indicate that the FD extract at high dose could have played a role in decreasing tumor aggressiveness. CCND1 gene is a positive regulator of cell cycle [31], and the overexpression of CCND1 in OSCC has been associated with a shorter survival rate of cancer patients [32,33]. In addition, Wilkey et al. [34] reported in an animal study that CCND1 overexpression increases the susceptibility of the mice towards oral carcinogenesis induced by 4NQO. ...
Background. The aim of this study is to evaluate the chemopreventive and chemotherapeutic activities of Ficus deltoidea (FD) in an animal model induced for oral cancer using 4-nitroquinoline-1-oxide (4NQO). Methods. Male Sprague-Dawley (SD) rats were randomized into six groups (n = 7 per group): Group 1 (untreated group); Group 2 (control cancer group) received 4NQO only for 8 weeks in their drinking water; Groups 3 and 4 (chemopreventive) received 4NQO for 8 weeks and were simultaneously treated with FD extract at 250 and 500 mg/kg, respectively, by oral gavage; Groups 5 and 6 (chemotherapeutic) received 4NQO for 8 weeks followed by the administration of FD extract at 250 and 500 mg/kg, respectively, for another 10 weeks. The incidence of oral cancer was microscopically evaluated. Moreover, immunohistochemical expression was analysed in tongue specimens using an image analyser computer system, while the RT² profiler PCR array method was employed for gene expression analysis. Results. The results of the present study showed a beneficial regression effect of the FD extract on tumor progression. The FD extract significantly reduced the incidence of oral squamous cell carcinoma (OSCC) from 100% to 14.3% in the high-dose groups. The immunohistochemical analysis showed that the FD extract had significantly decreased the expression of the key tumor marker cyclin D1 and had significantly increased the expression of the β-catenin and e-cadherin antibodies that are associated with enhanced cellular adhesion. Based on the gene expression analysis, FD extract had reduced the expression of the TWIST1 and RAC1 genes associated with epithelial-mesenchymal transition (EMT) and had significantly downregulated the COX-2 and EGFR genes associated with cancer angiogenesis, metastasis, and chemoresistance. Our data suggest that the FD extract exerts chemopreventive and chemotherapeutic activities in an animal model induced for oral cancer using 4NQO, thus having the potential to be developed as chemopreventive and chemotherapeutic agents.
1. Introduction
The third most common cancer in Malaysian Indian community is oral cancer [1], and it is highly associated with the practice of betel quid chewing, tobacco smoking, and excessive alcohol consumption [2]. Microorganisms that are present in the oral cavity can metabolize alcohol by enzymatic activity to acetaldehyde which is a known carcinogen [3]. Another well-known and potent carcinogen present in cigarette smoke [4], 4NQO, has been shown to induce oral cancer in animals when consumed in drinking water. The animal model for induction of oral cancer by 4NQO is widely used by the researchers for studying the process of carcinogenesis and for evaluating the effects of natural products on cancer development [5–7]. Over the years, the use of chemotherapeutic drugs such as cisplatin or allopathy medicine for treating cancer has been successful. However, this type of treatment modality is often associated with chemotherapeutic drugs toxicity, resulting in severe side effects. Moreover, around 90% of drug failures in metastatic cancers are caused by chemoresistance [8]. As a result, researchers have tried to look for other types of treatment modalities and these include the use of natural products for treating cancer.
Ficus deltoidea (FD) is one of the common medicinal plants used in Malaysia and other Southeast Asia countries. In Malaysia, the FD extract is used traditionally to heal wounds, sores, and rheumatism and can also be used as an antidiabetic drug or as an after-birth tonic. Despite all these traditional claims, scientific studies of this plant are very limited with most studies focusing on evaluating its antioxidant, antihyperglycemic, antinociceptive, antihypertensive, wound, and ulcer-healing properties [9]. It was reported in a study that 85 percent of the overall antioxidant activity of the FD extract was attributable to the flavan-3-ol monomers and the proanthocyanidins [10].
The anticancer activity of the FD extract against the human ovarian carcinoma cell line using a cell-based assay has been demonstrated [11]. Ware et al. [12] reported that the FD extract possesses potent natural antioxidant and anticancer activity when tested on prostate cancer DU145 cell line. Norrizah et al. [13] observed that the cytotoxic activity against the HL-60 cell line of the FD Leaf extract was more potent than the fruit extract. Besides that, when tested against the male reproductive system of the rats, there was a significant effect of the FD extract on the testes and epididymis weight, sperm count, and sperm viability [13]. There have been no in vivo studies showing the effects of FD extract towards oral cancer. Hence, this study was conducted to assess the chemopreventive and chemotherapeutic activities of the FD aqueous extract in an animal model induced for oral cancer using 4NQO.
2. Materials and Methods
The study was approved by the Institutional Animal Care and Use Committee (IACUC), University Malaya (Ethic reference no. 2016-190607/DENT/R/AMHS).
All experimental procedures were performed according to the FOM IACUC guidelines. All rats received human care based on the criteria summarized in the “Guide for the care and use of laboratory animals” (USA) [14].
2.1. 4-Nitroquinoline-1-oxide and Aqueous Extract of Ficus deltoidea
4-Nitroquinoline-1-oxide (4NQO) is a carcinogenic chemical. 4NQO may naturally occur in the environment but is typically manufactured for research purposes. 4NQO (Cas No. N-8141, Sigma Aldrich) was purchased from Labchem Sdn. Bhd., Malaysia.
The aqueous extract of FD was purchased from HCA Products Sdn Bhd. University Putra Malaysia, Selangor, Malaysia, with voucher number U1578/15. The aqueous extraction was done using FD leaves obtained from Herbagus Sdn Bhd according to the standardized 100% pure extraction method. The leaves of the plant were dried and powdered mechanically. The dried powdered leaves (100 g) were infused in distilled water at 60°C for 4 hours and filtered, and the liquid extract content was spray-dried for 6 hours at 80°C.
2.2. Animals
A total of 42 healthy male Sprague-Dawley (SD) rats (6–8 weeks old with body weight between 200–250 g) were obtained from the Animal Experimental Unit, Faculty of Medicine, University of Malaya, Kuala Lumpur. The animals were maintained under environmental condition of the animal house and had free access to standard ad libitum rat chow diet and fresh reverse osmosis (RO) water. They were housed in animal cages in an air-conditioned area at 22 ± 30°C and with a 12 h light/dark cycle in an experimental room. In order to ensure the animals were adapted to the laboratory condition, they were housed at the animal unit for 7 days before the experiments.
2.3. Dose Selection
The dose of 4NQO used in the present study was 20 ppm, and this dose was chosen based on many previous studies as it has been shown that oral cancer was successfully induced in Sprague Dawley rat model when 20 ppm of 4NQO agent dissolved in drinking water was administrated for 8 weeks [15, 16].
In this study, the doses of 250 and 500 mg/kg were chosen for the FD extract based on the previous studies. The dose of 2500 mg/kg when used in a subchronic toxicity study was discovered to be nontoxic [17, 18]. Thus, we have chosen to use 1/10th of maximum tolerable dose for therapeutic purpose [19], which were 250 and 500 mg/kg representing the low and higher doses.
2.4. Study Design
2.4.1. Induction of Oral Carcinogenesis by 4NQO
4-Nitroquinoline-1-oxide (4NQO), a water-soluble quinoline derivative, can produce tongue neoplastic and preneoplastic lesions. Drinking water containing 4NQO was freshly prepared twice a week in RO water and was administered to the rats in light-shielded water bottles (to protect the prepared solution from any unwanted effect of light exposure) at the concentration of 20 ppm for 8 weeks [16].
2.4.2. Chemopreventive Study
In order to evaluate the effect of the FD extract during the initiation phase of 4NQO-induced oral carcinogenesis, a chemopreventive study was designed in male SD rats. The rats were randomized into 4 groups of 7 rats per group. Group 1 was given normal RO water (untreated control), while the remaining 3 groups of rats (Groups 2, 3, and 4) were given 4NQO (Sigma Aldrich) solution as drinking water for 8 weeks as previously described [20, 23]. The 3 groups also received vehicle (water), FD extract at 250 and 500 mg/kg, respectively, daily in a volume of 10 ml/kg body weight, starting one week before the consumption of 4NQO, and this was continued for another week when the consumption of 4NQO has completed. Following this, the animals in all groups were switched back to RO water, and this continued until the end of this study at 22 weeks.
2.4.3. Chemotherapeutic Study
To evaluate the effect of the FD extract in the postinitiation phase of the oral cancer induction using 4NQO in an animal model, chemotherapeutic study was designed. A total of 14 male SD rats were randomized into 2 groups (Group 5 and 6) of 7 rats per group. The rats from groups 5 and 6 were given 4NQO (Sigma Aldrich) solution as drinking water for 8 weeks. Following this at the 9th week, Groups 5 and 6 were administrated with the FD extract at 250 and 500 mg/kg respectively, for another 10 weeks. The FD administration started 1 week after the cessation of the 4NQO treatment [20, 21]. Both of the control groups (Group 1—untreated and Group 2—cancer induced) that were involved in the chemopreventive study were also used in the chemotherapeutic study since both experiments were carried out at the same time (Figure 1). For both chemopreventive and chemotherapeutic studies, the observation of the overall health and behavior of the rats was done once a day to identify possible toxicities that may have resulted from the administration of the 4NQO carcinogen. The body weight of the rats was recorded every week during the study. The experiment was terminated on the 22nd week. General anesthesia was induced through the administration of an intramuscular injection of 5 mg/kg of xylazine 100 mg/ml and 50 mg/kg ketamine 100 mg/ml. As previously described by Stokes et al. [22], the rats were sacrificed through cervical dislocation and was followed by the excision of the whole tongue.
... 18 Anoctamin-1 (ANO1) is one of the human chloride channel proteins and is encoded by the ANO1 gene located on 11q13, 19 which is frequently amplified in different types of human carcinomas. 20,21 The expression of ANO1 is usually upregulated in several cancers including breast cancer, 22 prostate cancer, 23 27 and so on. It also plays an important role in the development of distant metastasis and poor prognosis of cancer patients. ...
Objective
: Chemotherapy failure derived from drug resistance is the most important reason causing the recurrence in colorectal cancer patients. Therefore, it is necessary to shed light on the mechanism of chemotherapy resistance in colorectal cancer patients.
Methods
: We looked into the contribution of Fusobacterium nucleatum and ANO1 to chemoresistance in the human colorectal carcinoma cell lines. We silence and overexpress ANO1 in HCT116 and HT29 cells with lentivirus and siRNA knockdown technique in the absence or presence of F. nucleatum, oxaliplatin or 5-fluorouracil (5-FU). ANO1, p-pg, cleaved PARP, cleaved caspase-3, and EGFR expression was measured by Western blot. Cell apoptosis was measured by flow cytometry.
Results
: We found that F. nucleatum promoted ANO1 expression on colon cancer cells. Moreover, ANO1 prevent colon cancer apoptosis from oxaliplatin and 5-FU. Additionally, knockdown ANO1 expression could block F. nucleatum protective effects and increase the apoptosis effects induced by oxaliplatin and 5-FU. Therefore, F. nucleatum might be biologically involved in the development of colon cancer chemoresistance via ANO1 pathway.
Conclusions
: Taken together, our findings provide a valuable insight into clinical management and therapy, which may ameliorate colorectal cancer patient outcomes.
... Head and neck cancer (HNC) is the 6 th most prevalent cancer worldwide [1]. The incidence of oropharyngeal cancer (OPC), a subset of HNC localized to the tonsils, the base of the tongue, and the soft palate/pharyngeal wall, is increasing, particularly human papillomavirus (HPV)associated OPC [2]. HPV-positive OPC has been linked to male gender, younger age, and white race [3]. ...
Background:
The incidence of oropharyngeal cancer (OPC) is increasing, particularly human papillomavirus (HPV)-associated OPC. The aim of this study was to specify the total societal cost of OPC by HPV status, cancer stage, and subsite using a bottom-up cost-of-illness approach.
Methods:
We analyzed 121 consecutive patients with OPC from the Southern Health Care Region of Sweden. We estimated the direct medical costs and indirect costs (e.g., disease-related morbidity and premature death) from 1 month prior to OPC diagnosis until 3 years after treatment completion.
Results:
The mean total cost per patient was €103 386 for HPV-positive and €120 244 for HPV-negative OPC. Eighty-one percent of the patients analyzed were HPV-positive: Accordingly, HPV-positive OPC represented 79% of the total cost of OPC. The mean total cost of stage I, II, III, IVA, IVB, and IVC, regardless of HPV status, was €59 424, €57 000, €69 246, €115 770, €234 459, and €21 930, respectively, of which indirect costs were estimated at €22 493 (37.8%), €14 754 (25.9%), €28 681 (41.4%), €67 107 (58%), €166 280 (70.9%), and €0. Tonsillar cancer represented 64% of OPC, with a mean total cost of €117 512 per patient.
Conclusion:
The societal cost of OPC is substantial. HPV-associated OPC comprises 79% of the total cost of this disease. The data presented in this study may be used in analytical models to aid decision makers in determining the potential value of gender-neutral HPV vaccination.
