Mucosal Cancer Research Articles

Low Expression of Mucin 2, High Expression of Mucin 13, and High Expression of Nuclear Factor Kappa-Light-Enhancer of Activated B Cells were Significant Pathways in Colorectal Cancer Development.

To prove the role of MUC2, MUC13, and NFκB protein expression as significant carcinogenesis pathways in colorectal cancer development. This is a nested case-control study conducted at the Udayana University, Sanglah General hospital, from September 2020 to 2021. All eligible subjects who visited the Digestive Surgery outpatient clinic with a colorectal surgery plan 2021 were included. The subjects were classified as case group (cancerous colonic mucosa) and control group (normal colonic mucosa), proved by histopathology examination. The parameters in this study were the expression of MUC2, MUC13, and NFκB by immunohistochemistry analysis. The data in this study will be collected and tabulated in SPSS 25.0 (Chicago, Illinois, USA). A total of 36 subjects with colorectal cancer (case group) and 36 subjects with normal colonic mucosa (control group) were analyzed in this study. The cancerous colonic mucosa significantly had a lower MUC2, higher MUC13, and higher NFκB expression. After multivariate analysis for controlling the age variable, the result showed that only MUC2, MUC13, and NFκB expressions were still significant with p<0.05. The effect from MUC2, MUC13, and NFκB expression totally could assess up to 85.4% of the risk of developing colorectal cancer. There was a significantly lower MUC2, higher MUC13, and higher NFκB expression in the carcinogenesis of colorectal cancer, representing the influence of the inflammatory pathway and the abnormality of the protective barrier. Therefore, in the future, this result could remark a future early prediction or scoring system to assess colorectal cancer in clinical application.

Transduodenal ampullectomy for early ampullary cancer: Clinical management, histopathological findings and long-term outcomes atasingle center.

Transduodenal ampullectomy has been attempted in ampullary tumors, including early ampullary cancer. However, the indication and extent of transduodenal ampullectomy with curative intent remain controversial. Herein, we address the perioperative and long-term outcomes of patients with early ampullary cancer who underwent transduodenal ampullectomy at a single center. We retrospectively enrolled 10 early ampullary cancer patients who underwent transduodenal ampullectomy and 11 early ampullary cancer patients who underwent subtotal stomach-preserving pancreatoduodenectomy at Saitama Cancer Center between October 2008 and May 2021. Among this cohort, we analyzed the perioperative outcomes and long-term outcomes. In terms of the perioperative outcomes between the transduodenal ampullectomy and subtotal stomach-preserving pancreatoduodenectomy groups, the transduodenal ampullectomy group exhibited a shorter operating time (244 minutes vs 390 minutes, P= .003), less intraoperative blood loss (67.5grams vs 774 grams, P= .006) and shorter length of postoperative hospital stay (15 days vs 33 days). With respect to the postoperative nutrition status, the transduodenal ampullectomy group exhibited less postoperative weight loss (0.67% vs 8.95%, P= .021), a better Controlling Nutritional Status score (1.0 vs 2.1, P= .011) and a better Prognostic Nutritional Index score (42.9 vs 40.9, P= .018). The 5-year survival in the adenoma with high-grade dysplasia and T1 ampullary cancer which invaded the mucosal layer groups was 100%, whereas the median survival time in the T1 ampullary cancer which invaded the sphincter of Oddi group was 20.7 months (P= .0028). Transduodenal ampullectomy is assumed to be a feasible and effective surgical procedure for the treatment of selected patients with early ampullary cancer, including patients with adenoma with high-grade dysplasia or T1 ampullary cancer which invaded the mucosal layer ampullary cancer.

Phenylboronic acid-functionalized chitosan for enabling transmucosal delivery for cancer therapy

Mucosa administration and transmucosal polymeric carriers demonstrate specific advantages in locoregional therapy, which, however, suffer from unsatisfactory transmucosal delivery efficiency and limited hydrophobic or bio-macromolecular drug loading. Herein, we demonstrate several phenylboronic acid-modified chitosan derivatives to screen out a self-assembly nano-system. The phenylboronic acid unit synthesized in chitosan skeleton (CS) afforded donor–acceptor coordination with amidogen of pirarubicin (THP) and aPD-1[1–3],the drug loading content was increased from 18.2 ± 0.4% to 37.0 ± 1.0% compared with CS. Besides, the phenylboronic acid modification provided an additional transmucosal advantage for cationic CS via non-covalent binding with mucosal glycosaminoglycans and enhanced the penetration ability of drugs through the endocytosis, Golgi-endoplasmic reticulum and exocytosis pathway. Furthermore, the encapsulated agents can be selectively released in response to the high reactive oxygen species concentration in tumor tissues, which combined with enhanced transmucosal capacity extremely contribute to improving the therapeutic efficacy and biosafety of BCS@THP and BCS@aPD-1 NPs in bladder cancer perfusion therapy as well as lung cancer inhalation treatment. Even more exciting is that in addition to THP and aPD-1, our platform could be easily extended to other chemotherapeutics and bio-macromolecular agents with electron-donating groups, rendering a simple and robust strategy for enabling highly efficient mucosal administration-based cancer therapy.

Development of pH-Responsive N-benzyl-N-O-succinyl Chitosan Micelles Loaded with a Curcumin Analog (Cyqualone) for Treatment of Colon Cancer.

This work aimed at preparing nanomicelles from N-benzyl-N,O-succinyl chitosan (NBSCh) loaded with a curcumin analog, 2,6-bis((3-methoxy-4-hydroxyphenyl) methylene) cyclohexanone, a.k.a. cyqualone (CL), for antineoplastic colon cancer chemotherapy. The CL-loaded NBSCh micelles were spherical and less than 100 nm in size. The entrapment efficiency of CL in the micelles ranged from 13 to 39%. Drug release from pristine CL was less than 20% in PBS at pH 7.4, whereas the release from CL-NBSCh micelles was significantly higher. The release study of CL-NBSCh revealed that around 40% of CL content was released in simulated gastric fluid at pH 1.2; 79 and 85% in simulated intestinal fluids at pH 5.5 and 6.8, respectively; and 75% in simulated colonic fluid at pH 7.4. CL-NBSCh showed considerably high selective cytotoxicity towards mucosal epithelial human colon cancer (HT-29) cells and lower levels of toxicity towards mouse connective tissue fibroblasts (L929). CL-NBSCh was also more cytotoxic than the free CL. Furthermore, compared to free CL, CL-NBSCh micelles were found to be more efficient at arresting cell growth at the G2/M phase, and induced apoptosis earlier in HT-29 cells. Collectively, these results indicate the high prospective potential of CL-loaded NBSCh micelles as an oral therapeutic intervention for colon cancer.

Experimental model of precancerous lesions of the oral mucosa

Oral mucosal cancer (OMC) is a serious public health problem. Studies were performed on 210 males of white mongrel rats weighing 180–200 g. The animals were randomly divided into 3 groups of 7 subgroups, with 10 rats in each group. The rats of the first group were included in the diet by dissolving a solution 4-NQO (carcinogen) in drinking water at a concentration of 50 mg/ml. The animals of the second group were applied by carcinogen dissolved in drinking water at a concentration of 50 mg/ml to the ОМС of the lower lip and the tongue three times a day (at 9:00, 2:00, and 7:00 pm) in combination with exposure to a 3D device with a traumatic element.The method of experimental modeling of pre-tumor lesions of the oral mucosa was developed. It included a combined local exposure to the solution 4-NQO and the 3D device with a traumatic element on the rat lower lip OMC. It has the following advantages over the existing models: the development of hyperplasia and dysplasia of lower lip ОМС epithelium is achieved after 12 weeks in 100 % of animals, and in the comparison group – in 20 % of rats (р &lt; 0.05); no carcinogen affection of other gastrointestinal organs, as indicated by no reduction of live body weight gain before the development of ОМС changes required from the experimental model (р &gt;&lt; 0.05); visually accessible localization of pathological epithelial changes on the lower lip ОМС, and in the comparison group on the tongue root.&gt;

The caspase-8 and procaspase-3 expression in gastric cancer and non-cancer mucosa in relation to clinico-morphological factors and some apoptosis-associated proteins

PurposeThe aim of the study was to assess the expression of caspase-8 and procaspase-3 proteins in gastric cancer (GC) cells and non-cancerous mucosa in relation to clinical and morphological characteristics of the tumor, postoperative survival as well as other apoptosis-related proteins. Materials and methodsThe study included 91 ​GC patients. Expression of the proteins was assessed using immunohistochemical method. ResultsPositive expression of procaspase-3 was found in all GC cells. A significant difference was found between high expression of this protein in cancer cells (70.3%) and non-cancerous mucosa (1.25%) (p ​≤ ​0.05). Caspase-8 expression was observed in 50.7% of GC cells and 46.7% of mucosa. Caspase-8 was more common in Lauren type II compared to Lauren type I cancer (p ​= ​0.009), while a statistically significant difference was reported between positive procaspase-3 expression and differentiation of GC (p ​= ​0.043) and Lauren's classification (p ​= ​0.028). We observed a significant positive correlation between the expression of caspase-8 and bcl-xl (p ​= ​0.030) as well as between the procaspase-3 and BID (p ​= ​0.026). Positive caspase-8 expression was associated with longer survival of GC patients (p ​≤ ​0.01). ConclusionsOur findings indicate the potential role of the analyzed proteins in GC pathogenesis. Positive expression of caspase-8 is associated with longer survival and better patient prognosis.

Increased CD4/CD8 Lymphocyte ratio predicts favourable neoadjuvant treatment response in gastric cancer: A prospective pilot study.

Despite optimal neoadjuvant chemotherapy only 40% of gastric cancer tumours achieve complete or partial treatment response. In the absence of treatment response, neoadjuvant chemotherapy in gastric cancer contributes to adverse events without additional survival benefit compared to adjuvant treatment or surgery alone. Additional strategies and methods are required to optimize the allocation of existing treatment regimens such as FLOT chemotherapy (5-Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel). Predictive biomarkers detected using immunohistochemistry (IHC) methods may provide useful data regarding treatment response. To investigate the utility of CD4, CD8, Galectin-3 and E-cadherin in predicting neoadjuvant FLOT chemotherapy tumour response in gastric adenocarcinoma. Forty-three adult patients with gastric adenocarcinoma, of which 18 underwent neoadjuvant chemotherapy, were included in a prospective clinical cohort. Endoscopic biopsies were obtained from gastric cancer and normal adjacent gastric mucosa. Differences in expression of Galectin-3, E-cadherin, CD4+ and CD8+ molecules between tumours with and without treatment response to neoadjuvant chemotherapy were assessed with IHC. Treatment response was graded by clinical pathologists using the Tumour Regression Score according to the College of American Pathologists criteria. Treatment response was defined as complete or near complete tumour response, whereas partial or poor/no response was defined as incomplete. Digital IHC images were annotated and quantitatively assessed using QuPath 0.3.1. Biomarker expression between responsive and incomplete response tumours was assessed using a two-sided Wilcoxon test. Biomarker expression was also compared between normal and cancer tissue and between 15 paired tumour samples before and after chemotherapy. We performed a preliminary multivariate analysis and power analysis to guide future study. Statistical analyses were completed using R 4.1.2. The ratio between CD4+ and CD8+ lymphocytes was significantly greater in treatment responsive tumours (Wilcoxon, P = 0.03). In univariate models, CD4+/CD8+ ratio was the only biomarker that significantly predicted favourable treatment response (Accuracy 86%, P < 0.001). Using a glmnet multivariate model, high CD4+/CD8+ ratio and low Galectin-3 expression were the most influential variables in predicting a favourable treatment response. Analyses of paired samples found that FLOT chemotherapy also results in increased expression of CD4+ and CD8+ tumour infiltrating lymphocytes (Paired Wilcoxon, P = 0.002 and P = 0.008, respectively). Our power analysis suggests future study requires at least 35 patients in each treatment response group for CD8 and Galectin-3 molecules, whereas 80 patients in each treatment response group are required to assess CD4 and E-cadherin biomarkers. We demonstrate that an elevated CD4+/CD8+ Ratio is a promising IHC-based biomarker to predict favourable treatment response to FLOT neoadjuvant chemotherapy in locally advanced gastric cancer.

Clinical outcomes of colonoscopic polypectomy with strategic surveillance colonoscopies in patients with 10 or more polyps

The clinical usefulness of repeat colonoscopic polypectomy in patients with numerous polyps has not been sufficiently determined. We aimed to analyze the clinical outcomes of colonoscopic polypectomy with surveillance colonoscopies in patients with ≥ 10 polyps. We reviewed the medical records of 152 patients who underwent polypectomy of ≥ 10 polyps at the baseline colonoscopy. We investigated polyp number, polyp size, polypectomy method, procedure time, and adverse events of the baseline colonoscopy. We also investigated the frequency and interval of surveillance colonoscopies and their findings. The mean number of polyps detected at the baseline colonoscopy was 20.0, of which 16.0 polyps were endoscopically resected. The mean size of the largest polyp was 13.4 mm. The mean procedure time was 54.9 min. Post-polypectomy bleeding occurred in 6 (3.9%) patients, all of whom were treated conservatively. No patients developed perforation. With an increasing number of surveillance colonoscopies, the number of detected polyps and the procedure time decreased. Surveillance colonoscopies identified colorectal cancer only in three patients (2.0%), all of which were mucosal cancers that could be curatively treated by polypectomy. Colonoscopic polypectomy with repeat surveillance colonoscopies is a clinically effective, efficient, and safe management option in patients with ≥ 10 polyps.

Expression of Connexins 37, 40 and 45, Pannexin 1 and Vimentin in Laryngeal Squamous Cell Carcinomas.

Thirty-four patients who underwent (hemi-)laryngectomy and regional lymphadenectomy due to LSCC from 2017 to 2018 in University Hospital Split, Croatia, were studied. Samples of tumor tissue and adjacent normal mucosa embedded in paraffin blocks were stained using the immunofluorescence method and were semi-quantitatively analyzed. The expression of Cx37, Cx40, and Panx1 differed between cancer and adjacent normal mucosa and between histological grades, being the highest in well-differentiated (G1) cancer and low/absent in poorly differentiated (G3) cancer (all p < 0.05). The expression of vimentin was the highest in G3 cancer. Expression of Cx45 was generally weak/absent, with no significant difference between cancer and the controls or between grades. Lower Panx1 and higher vimentin expression were found to be prognostic factors for regional metastatic disease. Lower Cx37 and 40 expressions were present in patients with disease recurrence after the three-year follow-up period. Cx37 and Cx40, Panx1, and vimentin have the potential to be used as prognostic biomarkers for LSCC.

Endoscopic submucosal dissection in early gastric cancer with papillary histological type.

412 Background: Gastric papillary adenocarcinoma has been regarded as differentiated-type adenocarcinomas along with well- or moderately-differentiated tubular adenocarcinomas in current endoscopic submucosal dissection (ESD) indication. We aimed to investigate lymph node metastasis (LNM) and to verify the safety of ESD in patients with papillary early gastric carcinoma (P-EGC). Methods: 4,264 patients with early gastric cancer (EGC) underwent curative gastrectomy between October 2000 and December 2017 at National Cancer Center, Korea. Among them, 45 patients were pathologically confirmed with P-EGC. We compared clinicopathological factors among differentiated-type EGC except P-EGC (n=2,106), undifferentiated-type EGC (n=2,113), and P-EGC. Logistic regression model was used to investigate risk factors of LNM. Results: P-EGCs were frequently located in lower third of the stomach (71.1%, P &lt; 0.001), and about half of them (46.7%, P &lt; 0.001) had elevated morphology. Mucosal cancer of P-EGC (37.9%) was significantly lower than differentiated-type (48.8%) and undifferentiated-type EGC (22.2%, P &lt; 0.001). Angiolymphatic invasion and LNM occurred most frequently in P-EGC (46.9% and 20.0%, respectively) compared to differentiated-type (18.9% and 9.2%, respectively) and undifferentiated-type EGCs (10.9% and 11.7%, respectively; P &lt; 0.001 and P = 0.004, respectively). P-EGC that was not mixed with other pathological type tended to have increased risk of LNM referent to differentiated EGC. (Odd ratio [OR] 2.53, 95% confidence interval [CI], 0.99-6.50). Among 45 patients with P-EGC, 13 patients met the current ESD indication; 3 patients corresponded to absolute indication and 10 patients did expanded indication. One patient had LNM and met expanded criteria with submucosal invasion less than 500 μm. In multivariate analysis, OR for LNM meeting expanded indication of P-EGC was 40.67 (95% CI, 2.54-702.76) referent to that of absolute indication compared to LNM meeting expanded indication of non-papillary EGC (10.28, 95% CI, 1.37-77.04). Conclusions: When ESD was applied to P-EGC, it should be carefully performed because of high rate of submucosal invasion and high risk of LNM even in with submucosal invasion less than 500 μm.

Immunohistochemistry examination to reveal the pathogenesis of Oral Squamous Cell Carcinoma

Oral mucosal cancer is a type of cancer that develops from the lining of the oral cavity (mucosa). The main risk factors are smoking and drinking alcohol. The pathogenesis of oral mucosal cancer involves various interrelated etiologies such as smoking and alcohol consumption, human papilloma virus (HPV), and patients who have undergone hemopoietic stem cell transplants (stem cell transplants). Meanwhile, it does not rule out the possibility of internal factors such as genetics. There are several types of oral mucosal cancer, but oral squamous cell carcinoma is the most common type of oral cancer and represents more than 90% of all head and neck cancers. Immunohistochemical examination of the Oral squamous cell carcinoma smear biopsy material which included examination of antibodies in the form of cytokeratin, CDT1, Ki-67, Geminin, Mcm2, γ-H2A/ histone family member X and Aurora-A, BCL-2, VEGF, p53, p63, p,73, Prb, c-erbB2 or HER2/neu, upregulation of telomerase (human telomerase reverse transcriptase; hTERT), loss of heterozygosity (Chromosome loci 3p, 8p, 9p, 4q, 11q, 13q, 17p), High-risk Human papillomavirus 16/18 (HR-HPV16 and 18), p16, Overexpression of EGFR, c-jun, c-fos, surviving (BIRC5), MMP-9, MMP9, TGF-, COX-1, and-2, and amplification of Cyclins D and E. Thus, paving the way for appropriate therapy.

Differences in color between early gastric cancer and cancer-suspected non-cancerous mucosa on linked color imaging.

Background and study aims Linked color imaging (LCI) can enhance the original color of each area and may useful to detect tumorous lesions during esophagogastroduodenoscopy. However, LCI may also enhance cancer-suspected non-cancerous regional color change. We conducted a retrospective image analysis to investigate the color characteristics of early gastric cancer (EGC) and cancer-suspected non-cancerous mucosa (CSM) in LCI. Methods LCI images of both EGC and CSM were retrospectively collected from the database of the institution. Fifteen endoscopists individually judged each image as EGC or CSM. The color difference between the inside and outside of the lesions was measured by CIE-Lab analysis in both groups and compared. Results A total of 245 LCI images of EGC (169) and CSM (76) were extracted and randomly lined for image collection. The test by the endoscopists showed accuracy, sensitivity, and specificity of 64.0 %, 63.7 %, and 64.0 %, respectively. Although the color difference between EGC and CSM was almost the same (12.5 vs. 12.9, not significant), each parameter of ΔL (bright: -0.3 vs. -2.7, P < 0.001), Δa (Reddish: 7.2 vs. 9.6, P = 0.004), and Δb (Yellowish: 6.4 vs. 3.8, P < 0.001) was significantly different in the groups. The color feature of both positive ΔL and Δb to EGC showed accuracy, sensitivity, and specificity of 54.7 %, 39.6 %, 88.2%, respectively. Conclusions The total color difference was almost the same between EGC and CSM; however, their color tones were different on linked color imaging. Although the color characteristics of EGC had high specificity, they also had low sensitivity.

Ball Valve Syndrome Treated by Endoscopic Submucosal Dissection.

An 85-year-old female was diagnosed with cerebellar hemorrhage based on computed tomography (Figure A). She underwent a craniotomy to remove the hematoma. It has been 2 months since she started rehabilitation after the craniotomy but she still experiences repeated vomiting. Therefore, gastrointestinal transit disorders were considered a differential diagnosis. An esophagogastroduodenoscopy was performed for a detailed examination, which revealed an erythematous, mobile, and semi-pedunculated lesion approximately 40 mm in size near the pyloric ring in the gastric antrum. The lesion was entrapped in the duodenal bulb (Figure B and Figure C). With a diagnosis of early gastric cancer resulting in ball valve syndrome, endoscopic submucosal dissection was performed for symptom relief. A pathological examination demonstrated that the tumor was a mucosal gastric cancer and had been completely resected with free vertical and horizontal margins (Figure D and Figure E). The patient tolerated a progressive diet with no recurrence of vomiting after treatment. Although repeated vomiting is often an aftereffect of cerebrovascular disease, gastrointestinal transit disorders should be considered as possible causes in cases of persistent vomiting because elderly patients are also at the risk of the development of gastrointestinal neoplasms. Endoscopic submucosal dissection was effective for the treatment of ball valve syndrome caused by gastric cancer. We thank Natsuko Nakano for the pathological examination and Yo Matsui for the radiological diagnosis.

TfR associated with cervical cancer with or without neoadjuvant chemotherapy

The objectives of this study was to examine the role of transferrin receptor (TfR) in the treatment of cervical cancer. Demographic and cancer-specific data were collected prospectively. Cancerous and adjacent mucosa tissues with neoadjuvant chemotherapy (NACT) or surgery alone were collected. TfR mRNA and protein expression was measured by Quantitative reverse transcription PCR (RT-qPCR) and immunoblots. We measured the cell viability by the MTT (3- [4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay with or without TfR-siRNA transfection. All 42 patients aged 49.31 ± 6.30 years with locally advanced cervical cancer were included: NACT (n = 22), surgery alone (n = 20). Quantitative results showed that the levels of TfR mRNA &amp; protein in cancerous tissues were higher than those in adjacent mucosal tissues. We also demonstrated that the levels of TfR mRNA and protein were lower in tumor tissues collected from patients with NACT than in those collected from patients without NACT. We also observed that silencing of the TfR gene suppressed the survival of HeLa cells (48 h, p &lt; 0.05). Our findings suggest a potential value for TfR as a diagnosis or evaluation marker for cervical cancer. The present study suggests that si-TfR may have an antitumou effect against cervical cancer cells, probably by limiting cell proliferation and reducing the TfR mRNA and protein levels.

Perspicacity into the role of psychological factors in oral mucosal cancer: A synopsis

Perspicacity into the role of psychological factors in oral mucosal cancer: A synopsis

Prognostic relevance of pre-treatment inflammatory biomarkers along with other clinicopathological and treatment factors in oral cavity cancers.

Inflammation has traditionally been considered to be one of the hallmarks of cancer, and systemic inflammatory responses have a prognostic value in many solid cancers. The use of inflammation-based prognostic markers along with traditional clinicopathological prognostic markers in oral cavity cancers has not been studied well. This is a retrospective study from a prospectively maintained database of patients with oral cancers who were managed in a regional cancer center in south India. The study included patients with squamous cell carcinoma of the oral cavity who were treated with curative intent from January to December 2016. Three hundred sixty-one patients met the eligibility criteria and were included in the study. The median age of our patient cohort was 45 years; the male-to-female ratio was 3.7:1. All of the patients underwent curative treatments after a multi-disciplinary board concurrence. Advanced T stage, patients with buccal mucosal cancers and patients who received upfront non-surgical treatments have poorer survival outcomes. The clinicopathological variables that predicted a poorer overall survival in the cohort of patients treated with upfront surgery were advanced T Stage, higher grade, presence of perineural invasion, a higher inflammatory maker, and combination of platelet and neutrophil lymphocyte ratio (COP-NLR). Our unique study of oral cavity cancer patients with a primary aim of exploring the prognostic significance of the pre-treatment inflammatory markers gave very interesting results. The prognostic significance of COP-NLR and other inflammatory markers in oral cancers need to be further explored. More importantly, our study has clearly reiterated that meaningful long-term survival outcomes in oral cavity cancers can only be achieved with the incorporation of upfront surgery.

017 Single-cell T cell receptor (TCR) repertoire of skin and blood reveals skin-specific characteristics in health and HIV infection

Human skin harbours a large proportion of the resident memory T (Trm) cells of the body. Trm cells promote immune homeostasis and exert anti-microbial and anti-cancer function in tissue. We recently demonstrated that skin Trm cells are permanently depleted in people living with HIV (PLWH) with a low nadir and possibly replaced by blood-derived T cells. We linked the loss of Trm cells in PLWH with the increased risk of developing cutaneous and mucosal cancer. The T-cell receptor (TCR) diversity analysis with next generation sequencing might give new insights into the biology of skin Trm cells at homeostasis and in HIV.

Electroporation in Head-and-Neck Cancer: An Innovative Approach with Immunotherapy and Nanotechnology Combination.

Squamous cell carcinoma is the most common malignancy that arises in the head-and-neck district. Traditional treatment could be insufficient in case of recurrent and/or metastatic cancers; for this reason, more selective and enhanced treatments are in evaluation in preclinical and clinical trials to increase in situ concentration of chemotherapy drugs promoting a selectively antineoplastic activity. Among all cancer treatment types (i.e., surgery, chemotherapy, radiotherapy), electroporation (EP) has emerged as a safe, less invasive, and effective approach for cancer treatment. Reversible EP, using an intensive electric stimulus (i.e., 1000 V/cm) applied for a short time (i.e., 100 μs), determines a localized electric field that temporarily permealizes the tumor cell membranes while maintaining high cell viability, promoting cytoplasm cell uptake of antineoplastic agents such as bleomycin and cisplatin (electrochemotherapy), calcium (Ca2+ electroporation), siRNA and plasmid DNA (gene electroporation). The higher intracellular concentration of antineoplastic agents enhances the antineoplastic activity and promotes controlled tumor cell death (apoptosis). As secondary effects, localized EP (i) reduces the capillary blood flow in tumor tissue ("vascular lock"), lowering drug washout, and (ii) stimulates the immune system acting against cancer cells. After years of preclinical development, electrochemotherapy (ECT), in combination with bleomycin or cisplatin, is currently one of the most effective treatments used for cutaneous metastases and primary skin and mucosal cancers that are not amenable to surgery. To reach this clinical evidence, in vitro and in vivo models were preclinically developed for evaluating the efficacy and safety of ECT on different tumor cell lines and animal models to optimize dose and administration routes of drugs, duration, and intensity of the electric field. Improvements in reversible EP efficacy are under evaluation for HNSCC treatment, where the focus is on the development of a combination treatment between EP-enhanced nanotechnology and immunotherapy strategies.

Combining Raman spectroscopy and machine learning to assist early diagnosis of gastric cancer

Gastric cancers, with gastric adenocarcinoma (GAC) as the most common histological type, cause quite a few of deaths. In order to improve the survival rate after GAC treatment, it is important to develop a method for early detection and therapy support of GAC. Raman spectroscopy is a potential tool for probing cancer cell due to its real-time and non-destructive measurements without any additional reagents. In this study, we use Raman spectroscopy to examine GAC samples, and distinguish cancerous gastric mucosa from normal gastric mucosa. Average Raman spectra of two groups show differences at 750 cm−1, 1004 cm−1, 1449 cm−1, 1089–1128 cm−1, 1311–1367 cm−1 and 1585–1665 cm−1, These peaks were assigned to cytochrome c, phenylalanine, phospholipid, collagen, lipid, and unsaturated fatty acid respectively. Furthermore, we build a SENet-LSTM model to realize the automatic classification of cancerous gastric mucosa and normal gastric mucosa, with all preprocessed Raman spectra in the range of 400–1800 cm−1 as input. An accuracy 96.20% was achieved. Besides, by using masking method, we found the Raman spectral features which determine the classification and explore the explainability of the classification model. The results are consistent with the conclusions obtained from the average spectrum. All results indicate it is potential for pre-cancerous screening to combine Raman spectroscopy and machine learning.

Cervical metastasis of undetermined origin: evaluation and criteria for management

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Cervical metastatic cancer of undetermined primary site is described as the presence of metastasis in the cervical lymph node(s) without any identifiable primary site, despite detailed clinical and investigative evaluations. Identification of primary origin is still a big challenge even in the phase of modern diagnostic options. This review was meant to lay open the challenges and offer options of evaluation and managing these cases in a resource limited environment.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; The literature search was carried out to retrieve relevant published articles, books, guidelines. The search was limited to articles in English while unpublished literatures were excluded. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The process of metastasis might begin before the obvious growth of the primary mass, making detection of primary site of a malignant tumour difficult to determine. There is no current worldwide consensus for evaluation and treatment of cervical metastasis of undetermined primary; however, the primary purpose for management should be towards cure along with locoregional control. This is always based on a well-studied natural history of the mucosal squamous cell cancers of the upper aerodigestive tract.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The first step in the work up remains thorough clinical evaluation and the minimum evaluation should include computed tomography scan of the head and neck, core needle biopsy of the metastatic cervical lymph node(s) for histological analysis, panendoscopy and biopsies from suspicious sites in the upper airway. Treatment modalities can be classified into modified radical neck dissection with or without adjuvant radiotherapy, radiotherapy alone, and combination of surgical intervention and chemoradiation.&lt;/p&gt;