Search results for: breast cancer diagnosis

Authors: Olivia Rachel Hwang, Yu-Hsuan Joni Shao

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Androgen Deprivation Therapy (ADT) has been a primary treatment for patients with advanced prostate cancer. However, it is associated with numerous adverse effects related to Metabolic Syndrome (MetS), including hypertension, diabetes, hyperlipidaemia, heart diseases and ischemic strokes. However, complications associated with ADT for prostate cancer in Taiwan is not well documented. The purpose of this study is to utilize the data from NHIRD (National Health Insurance Research Database) to examine the trajectory changes of MetS-related complications in men receiving ADT. The risks of developing complications after the treatment were analyzed with multivariate Cox regression model. Covariates including in the model were the complications before the diagnosis of prostate cancer, the age, and the year at cancer diagnosis. A total number of 17268 patients from 1997-2013 were included in this study. The exclusion criteria were patients with any other types of cancer or with the existing MetS-related complications. Changes in MetS-related complications were observed among two treatment groups: 1) ADT (n=9042), and 2) non-ADT (n=8226). The ADT group appeared to have an increased risk in hypertension (hazard ratio 1.08, 95% confidence interval 1.03-1.13, P = 0.001) and hyperlipidemia (hazard ratio 1.09, 95% confidence interval 1.01-1.17, P = 0.02) when compared with non-ADT group in the multivariate Cox regression analyses. In the risk of diabetes, heart diseases, and ischemic strokes, ADT group appeared to have an increased but not significant hazard ratio. In conclusion, ADT was associated with an increased risk in hypertension and hyperlipidemia in prostate cancer patients in Taiwan. The risk of hypertension and hyperlipidemia should be considered while deciding on ADT, especially those with the known history of hypertension and hyperlipidemia.

Keywords: androgen deprivation therapy, ADT, complications, metabolic syndrome, MetS, prostate cancer

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Authors: C. M. Williams, R. English, P. King, I. M. Brown

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Introduction: Pseudoangiomatous Stromal Hyperplasia (PASH) is a benign fibrous proliferation of breast stroma affecting predominantly premenopausal women with no significant increased risk of breast cancer. Informal recommendations for management have continued to evolve over recent years from surgical excision to observation, although there are no specific national guidelines. This study assesses the safety of a non-surgical approach to PASH management by review of cases at a single centre. Methods: Retrospective case series review (January 2011 – August 2016) was conducted on consecutive PASH cases. Diagnostic classification (clinical, radiological and histological), management outcomes, and breast cancer incidence were recorded. Results: 43 patients were followed up for median of 25 months (3-64) with 75% symptomatic at presentation. 12% of cases (n=5) had a radiological score (BIRADS MMG or US) ≥ 4 of which 3 were confirmed malignant. One further malignancy was detected and proven radiologically occult and contralateral. No patients were diagnosed with a malignancy during follow-up. Treatment evolved from 67% surgical in 2011 to 33% in 2016. Conclusions: The management of PASH has transitioned in line with other published experience. The preliminary findings suggest this appears safe with no evidence of missed malignancies; however, longer follow up is required to confirm long-term safety. Recommendations: PASH with suspicious radiological findings ( ≥ U4/R4) warrants multidisciplinary discussion for excision. In the absence of histological or radiological suspicion of malignancy, PASH can be safely managed without surgery.

Keywords: benign breast disease, conservative management, malignancy, pseudoangiomatous stromal hyperplasia, surgical excision

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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: Satoshi Furukawa, Satomu Morita, Katsuji Nishi, Masahito Hitosugi

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A 75-year-old woman took thyroidectomy forty years previously. Enlarged masses were seen at autopsy just above and below the left clavicle. We proved the diagnosis of papillary thyroid cancer (PTC) and lung metastasis by histological examinations. The prognosis of PTC is excellent; the 10-year survival rate ranges between 85 and 99%. Lung metastases may be found in 10% of the patients with PTC. We report an unusual case of recurrence of PTC with metastasis to the lung.

Keywords: papillary thyroid cancer, lung metastasis, autopsy, histopathological findings

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Authors: Kasi Viswanadh Matte, Abhisheh Kumar Mehata, M.S. Muthu

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Brest cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol succinate 1000 conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted and targeted nanoparticles were found to be in the range of 126-186 nm and 74-78% respectively. In-vitro, MDA-MB-231 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional nanoparticles. The IC50 values of non-targeted and targeted nanoparticles from cytotoxic assay were found to be 43 and 223 folds higher than DocelTM. The in-vivo pharmacokinetic study showed 2.33, and 2.82-fold enhancement in relative bioavailability of docetaxel for non-targeted and HER-2 receptor targeted nanoparticles, respectively than DocelTM, and after i.v administration, non-targeted and targeted nanoparticle achieved 3.48 and 5.94 times prolonged half-life in comparison to DocelTM. The area under the curve (AUC), relative bioavailability (FR) and mean residence time (MRT) were found to be higher for non-targeted and targeted nanoparticles compared to DocelTM. Further, histopathology results of non-targeted and targeted nanoparticles showed less toxicity on vital organs such as lungs, liver, and kidney compared to DocelTM.

Keywords: breast cancer, HER-2 receptor, targeted nanomedicine, chitosan, TPGS

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Authors: Nicole Ramlachan, Samuel Mark West

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Lung cancer is the leading cause of cancer-associated deaths in North America, with the vast majority being non-small cell lung cancer (NSCLC), with a five-year survival rate of only 24%. Non-invasive discovery of biomarkers associated with early-diagnosis of NSCLC can enable precision oncology efforts using liquid biopsy-based multiomics profiling of plasma. Although tissue biopsies are currently the gold standard for tumor profiling, this method presents many limitations since these are invasive, risky, and sometimes hard to obtain as well as only giving a limited tumor profile. Blood-based tests provides a less-invasive, more robust approach to interrogate both tumor- and non-tumor-derived signals. We intend to examine 30 stage III-IV NSCLC patients pre-surgery and collect plasma samples.Cell-free DNA (cfDNA) will be extracted from plasma, and next-generation sequencing (NGS) performed. Through the analysis of tumor-specific alterations, including single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs), and methylation alterations, we intend to identify tumor-derived DNA—ctDNA among the total pool of cfDNA. This would generate data to be used as an accurate form of cancer genotyping for diagnostic purposes. Using liquid biopsies offer opportunities to improve the surveillance of cancer patients during treatment and would supplement current diagnosis and tumor profiling strategies previously not readily available in Trinidad and Tobago. It would be useful and advantageous to use this in diagnosis and tumour profiling as well as to monitor cancer patients, providing early information regarding disease evolution and treatment efficacy, and reorient treatment strategies in, timethereby improving clinical oncology outcomes.

Keywords: genomics, multiomics, clinical genetics, genotyping, oncology, diagnostics

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Authors: Sally Shepherd, Richard De Boer, Craig Murphy

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Background: Invasive lobular carcinoma (ILC) can metastasize to atypical sites within the peritoneal cavity, gastrointestinal, or genitourinary tract. Management varies depending on the symptom presentation, extent of disease burden, particularly if the primary disease is occult, and patient wishes. Case Series: 6 patients presented with general surgical presentations of ILC, including incomplete large bowel obstruction, cholecystitis, persistent lower abdominal pain, and faecal incontinence. 3 were diagnosed with their primary and metastatic disease in the same presentation, whilst 3 patients developed metastasis from 5 to 8 years post primary diagnosis of ILC. Management included resection of the metastasis (laparoscopic cholecystectomy), excision of the primary (mastectomy and axillary clearance), followed by a combination of aromatase inhibitors, biologic therapy, and chemotherapy. Survival post diagnosis of metastasis ranged from 3 weeks to 7 years. Conclusion: Metastatic ILC must be considered with any gastrointestinal or genitourinary symptoms in patients with a current or past history of ILC. Management may not be straightforward to chemotherapy if the acute pathology is resulting in a surgically resectable disease.

Keywords: breast cancer, gastrointestinal metastasis, invasive lobular carcinoma, metastasis

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Authors: Naomi Sakamoto, Eisuke Fukuma, Mika Nashimoto, Yoshitomo Koshida

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Background: Selective localization of the metastatic lymph node with clip and removal of clipped nodes with sentinel lymph node (SLN), known as targeted axillary dissection (TAD), reduced false-negative rates (FNR) of SLN biopsy (SLNB) after neoadjuvant chemotherapy (NAC). For the patients who achieved nodal pathologic complete response (pCR), accurate staging of axilla by TAD lead to omit axillary lymph node dissection (ALND), decreasing postoperative arm morbidity without a negative effect on overall survival. This study aimed to investigate the ultrasound (US) identification rate and success removal rate of two kinds of ultrasound-visible clips placed in metastatic lymph nodes during TAD procedure. Methods: This prospective study was conducted using patients with clinically T1-3, N1, 2, M0 breast cancer undergoing NAC followed by surgery. A US-visible clip was placed in the suspicious lymph node under US guidance before neoadjuvant chemotherapy. Before surgery, US examination was performed to evaluate the detection rate of clipped node. During the surgery, the clipped node was removed using several localization techniques, including hook-wire localization, dye-injection, or fluorescence technique, followed by a dual-technique SLNB and resection of palpable nodes if present. For the fluorescence technique, after injection of 0.1-0.2 mL of indocyanine green dye (ICG) into the clipped node, ICG fluorescent imaging was performed using the Photodynamic Eye infrared camera (Hamamatsu Photonics k. k., Shizuoka, Japan). For the dye injection method, 0.1-0.2 mL of pyoktanin blue dye was injected into the clipped node. Results: A total of 29 patients were enrolled. Hydromark™ breast biopsy site markers (Hydromark, T3 shape; Devicor Medical Japan, Tokyo, Japan) was used in 15patients, whereas a UltraCor™ Twirl™ breast marker (Twirl; C.R. Bard, Inc, NJ, USA) was placed in 14 patients. US identified the clipped node marked with the UltraCore Twirl in 100% (14/14) and with the Hydromark in 93.3% (14/15, p = ns). Success removal of clipped node marked with the UltraCore Twirl was achieved in 100% (14/14), whereas the node marked with the Hydromark was removed in 80% (12/15) (p = ns). Conclusions: The ultrasound identification rate differed between the two types of ultrasound-visible clips, which also affected the success removal rate of clipped nodes. Labelling the positive node with a US-highly-visible clip allowed successful TAD.

Keywords: breast cancer, neoadjuvant chemotherapy, targeted axillary dissection, breast tissue marker, clip

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Authors: Hanan Alsaeid Alshenawy

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Background: Cervical dysplasia, which is potentially precancerous, has increased in young women. Detection of cervical is important for reducing morbidity and mortality in cervical cancer. This study analyzes the immunohistochemical expression of p16, HPV L1 capsid protein and Ki67 in cervical intraepithelial lesions and correlates them with lesion grade to develop a set of markers for diagnosis and detect the prognosis of cervical cancer precursors. Methods: 75 specimens were analyzed including 15 cases CIN 1, 28 CIN 2, 20 CIN 3, and 12 cervical squamous carcinoma, besides 10 normal cervical tissues. They were stained for p16, HPV L1 and Ki-67. Sensitivity, specificity, predictive values and accuracy were evaluated for each marker. Results: p16 expression increased during the progression from CIN 1 to carcinoma. HPV L1 positivity was detected in CIN 2 and decreased gradually as the CIN grade increased but disappear in carcinoma. Strong Ki-67 expression was observed with high grades CIN and carcinoma. p16, HPV L1 and Ki67 were sensitive but with variable specificity in detecting CIN lesions. Conclusions: p16, HPV L1 and Ki67 are useful set of markers in establishing the risk of high-grade CIN. They complete each other to reach accurate diagnosis and prognosis.

Keywords: p16, HPV L1, Ki67, CIN, cervical carcinoma

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

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

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

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Authors: Kabange Kasumbwe, Viresh Mohanlall, Bharti Odhav, Venu Narayanaswamy

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Coumarins are naturally occurring plant metabolites known for their pharmacological properties such as anticoagulant, antimicrobial, anticancer, antioxidant, anti-inflammatory and antiviral properties. The pharmacological and biochemical properties and curative applications of coumarins depend on the substitution around the coumarin core structure. In the present study, seven halogenated coumarins CMRN1-CMRN7 were synthesized and evaluated for their anticancer activity. The cytotoxicity potential of the test compounds was evaluated against UACC62 (Melanoma), MCF-7 (Breast cancer) and PBM (Peripheral Blood Mononuclear) cell lines using MTT assay keeping doxorubicin as standard drug. The apoptotic potential of the coumarin compounds was evaluated against UACC62 (Melanoma) cell by assessing their morphological changes, membrane change, mitochondria membrane potential; pro-apoptotic changes were investigated using the AnnexinV-PI staining, JC-1, caspase-3 enzyme kits respectively on flow cytometer. The synthetic coumarin has strongly suppressed the cell proliferation of UACC-62 (Melanoma) and MCF-7 (Breast) Cancer cells, the higher toxicity of these compounds against UACC-62 (Melanoma) and MCF-7 (Breast) were CMRN3, CMRN4, CMRN5, CMRN6. However, compounds CMRN1, CMRN2, and CMRN7 had no significant inhibitory effect. Furthermore the active compounds CMRN3, CMRN4, CMRN5, CMRN6 exerted antiproliferative effects through apoptosis induction against UACC-62 (Melanoma), suggesting their potential could be considered as attractive lead molecules in the future for the development of potential anticancer agents since one of the important criteria in the development of therapeutic drugs for cancer treatment is to have high selectivity and less or no side-effects on normal cells and these compounds had no inhibitory effect against the PBMC cells.

Keywords: coumarin, MTT, apoptosis, cytotoxicity

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Authors: S. Sakhri

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Background: The use of Zoledronic acid (ZA) is an established place in the treatment of malignant tumors with a predilection for the skeleton of interest (in particular metastasis). Although the main target of Zoledronic acid was osteoclasts, there are preclinical data suggest that Zoledronic acid may have an antitumor effect on cells other than osteoclasts, including tumor cells. Antitumor activity, including the inhibition of tumor cell growth and the induction of apoptosis of tumor cells, inhibition of tumor cell adhesion and invasion, and anti-angiogenic effects have been demonstrated. Methods. From (2012 to 2014), 438 patients were included respondents the inclusion criteria, respectively. This is a prospective study over a 4 year period. Of all patients (N=438), 432 received neoadjuvant chemotherapy with Zoledronic acid. The primary end point was the pathologic complete response in advancer breast cancer stage. The secondary end point is to evaluate Clinical response according to RECIST criteria; estimate the bone density before and at the end of chemotherapy in women with locally advanced breast cancer, Toxicity Evaluation and Overall survival using Kaplan-Meier and log test. Result: The Objective response rate was 97% after (C4) with 3% stabilizations and 99, 3% of which 0.7% C8 after stabilization. The clinical complete response was 28% after C4 respectively, and 46.8% after C8, the pathologic complete response rate was 40.13% according to the classification Sataloff. We observed that the pathologic complete response rate was the most raised in the group including Her2 (luminal Her2 and Her2) the lowest in the triple negative group as classified by Sataloff. We found that the pCR is significantly higher in the age group (35-50 years) with 53.17%. Those who have more than 50 years in 2nd place with 27.7% and the lower in young woman 35 years pCR was 19%, not statistically significant, -The pCR was also in favor of the menopausal group in 51, 4%, and 48, 55% for non-menopausal women. The average duration of overall survival was also significantly in the subgroup (Luminal -Her2, Her2) compared with triple negative. It is 47.18 months in the luminal group vs. 38.95 in the triple negative group. -Was observed in our study a difference in quality of life between (C1) was the admission of the patient, and after (C8), we found an increase in general signs and a deterioration in the psychological state C1, in contrast to the C8 these general signs and mental status improves, up to 12, and 24 months. Conclusion The results of this study suggest that the addition of ZA to néoadjuvant CT has potential anti-cancer benefit in patients (Luminal -Her2, Her2) compared with triple negative with or without menopause status.

Keywords: HER2+, RH+, breast cancer, tyrosine kinase

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Authors: Carlos Huertas, Reyes Juarez-Ramirez

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Public health is one of the most critical issues today; therefore, there is great interest to improve technologies in the area of diseases detection. With machine learning and feature selection, it has been possible to aid the diagnosis of several diseases such as cancer. In this work, we present an extension to the Heat Map Based Feature Selection algorithm, this modification allows automatic threshold parameter selection that helps to improve the generalization performance of high dimensional data such as mass spectrometry. We have performed a comparison analysis using multiple cancer datasets and compare against the well known Recursive Feature Elimination algorithm and our original proposal, the results show improved classification performance that is very competitive against current techniques.

Keywords: biomarker discovery, cancer, feature selection, mass spectrometry

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Authors: Khalid Al Saleh, Najlaa AlSayed

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Background: Palliative care is changing from just ‘end of life care’ to care delivered earlier in the disease course. Metanalysis showed that Palliative Performance Scale (PPS) is associated with increased length of survival. The Palliative Care Center (PCC) in Kuwait is the only stand-alone center in Eastern Mediterranean Region with a capacity of 92 beds. We compared clinical characteristics between patients referred from the Specialized Cancer Center and general hospitals in Kuwait to PCC. Method: A cross Sectional survey was conducted since the opening of PCC in January 2011 to June 2013. Patients’ data on demographics, type of the cancer, PPS score and referring hospital were collected and analyzed. Results: Total number of the patients was 142. Mean age was 61.05±14.79 years, 66 patients (47.1%) were males and 74 (52.9%) were females. The most common cancers in males were lung (n=18, 27.3%) followed by head and neck cancers (n=8, 12.1%) and brain tumors (n=7, 10.6%) while in females, the most common cancers were breast cancer (n=12, 16.7%) followed by ovarian cancer (n=10, 13.9%) and Cancer Colon (n=8, 11.1%). Patients with PPS score 30% were 27.9% (n=39), 40% in 40.7% (n=57), and 50% in 17.1% (n=24) respectively. Patients referred from the Specialized Cancer Center had significantly higher portion of patients with PPS score > 30% (73.4%, n=94), compared to patients coming from general hospitals (33.3%, n=4), P value= 0.007. Conclusion: There is significant difference in PPS scores between patients referred from the Specialized Cancer Center compared to patients referred from general hospitals. We encourage that all cancer patients should be treated in Specialized Cancer Centers and earlier involvement of Palliative Care Centers to achieve better survival. Training workshops are needed for health care professionals working in general hospitals to raise awareness about earlier referral of patients to palliative care services.

Keywords: palliative care, kuwait, performance scale differences, pps score, specialized hospitals

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Authors: Nusaiba Al-Nemrawi, Belal Al-Husein

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Methotrexate (MTX) is a stoichiometric inhibitor of dihydrofolate reductase, which is essential for DNA synthesis. MTX is a chemotherapeutic agent used for treating many types of cancer cells. However, cells’ resistant to MTX is very common and its pharmacokinetic behavior is highly problematic. of MTX within tumor cells, we propose encapsulation of antitumor drugs in nanoparticulated systems. Chitosan (CS) is a naturally occurring polymer that is biocompatibe, biodegradable, non-toxic, cationic and bioadhesive. CS nanoparticles (CS-NPs) have been used as drug carrier for targeted delivery. Titanium dioxide (TiO2), a natural mineral oxide, which is used in biomaterials due to its high stability and antimicrobial and anticorrosive properties. TiO2 showed a potential as a tumor suppressor. In this study a new formulation of MTX loaded in CS NPs (CS-MTX NPs) and coated with Titanium oxide (TiO2) was prepared. The mean particle size, zeta potential, polydispersity index were measured. The interaction between CS NPs and TiO2 NPs was confirmed using FTIR and XRD. CS-MTX NPs was studied in vitro using the tumor cell line MCF-7 (human breast cancer). The results showed that CS-MTX has a size around 169 nm and as they were coated with TiO2, the size ranged between and depending on the ratio of CS-MTX to TiO2 ratio used in the preparation. All NPs (uncoated and coated carried positive charges and were monodispersed. The entrapment efficacy was around 65%. Both FTIR and XRD proved that TiO2 interacted with CS-MTX NPs. The drug invitro release was controlled and sustained over days. Finally, the studied in vitro using the tumor cell line MCF-7 suggested that combining nanomaterials with anticancer drugs CS-MTX NPs may be more effective than free MTX for cancer treatment. In conclusion, the combination of CS-MTX NPs and TiO2 NPs showed excellent time-dependent in vitro antitumor behavior, therefore, can be employed as a promising anticancer agent to attain efficient results towards MCF-7 cells.

Keywords: Methotrexate, Titanium dioxide, Chitosan nanoparticles, cancer

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Authors: Srisopa Ruangnoo, Arunporn Itharat

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

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

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Authors: Kolja Them, Priyal Chikhaliwala, Sudeshna Chandra

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Purpose: The purpose of this work is to examine possibilities for noninvasive imaging and identification of tumor markers for cancer diagnosis. The proposed method uses antibody conjugated iron oxide nanoparticles and multicolor Magnetic Particle Imaging (mMPI). The method has the potential for radiation exposure free real-time estimation of local tumor marker concentrations in vivo. In this study, the method is applied to human Alpha-1-Fetoprotein. Materials and Methods: As tracer material AFP antibody-conjugated Dendrimer-Fe3O4 nanoparticles were used. The nanoparticle bioconjugates were then incubated with bovine serum albumin (BSA) to block any possible nonspecific binding sites. Parts of the resulting solution were then incubated with AFP antigen. MPI measurements were done using the preclinical MPI scanner (Bruker Biospin MRI GmbH) and the multicolor method was used for image reconstruction. Results: In multicolor MPI images the nanoparticles incubated only with BSA were clearly distinguished from nanoparticles incubated with BSA and AFP antigens. Conclusion: Tomographic imaging of human tumor marker Alpha-1-Fetoprotein is possible using AFP antibody conjugated iron oxide nanoparticles in presence of BSA. This opens interesting perspectives for cancer diagnosis.

Keywords: noninvasive imaging, tumor antigens, antibody conjugated iron oxide nanoparticles, multicolor magnetic particle imaging, cancer diagnosis

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Authors: Aref Zribi, Sonia Ben Nasr, Sana Fendri, Mahdi Balti, Abderazzek Haddaoui

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Background: Despite their benefit, Endocrine therapies (ET) are known to have substantial adverse events (AEs) such as hot flashes, mood disorders and osteoarticular pain. ET induced alopecia(EIA) is less frequently noted by patients and is less reported in the literature. The aim of our study was to report ET alopecia characteristics and their influence on patient and treatment observance. Method: We conducted a retrospective study including luminal BC patients treated in the oncology department of the military hospital of Tunis between January 2015 and December 2020. Patients treated with previous chemotherapy-inducing alopecia were excluded. Results: 145 female patients were included. The median age was 59 years. EIA was reported in 44% of cases. Alopecia was attributed to aromatase inhibitors in 53% and tamoxifen in 21%. Severity was grade 1 in 80% and grade 2 in the remaining cases. ET discontinuation because of alopecia was noted in 6.5 % of patients. Moderate improvement of alopecia was observed with topical minoxidil and Thallium metallicum 9CH homeopathy during ET in 60% of patients. Conclusions: EIA is frequent in BC patients and should be considered to improve treatment observance and patients’ quality of life.

Keywords: endocrine therapy, alopecia, breast cancer, Tunisia

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Authors: Ipsita Biswas, Arnab Sarkar, Ashikur Rahaman, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal

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One of the major reasons for the high mortality rate of lung cancer is the substantial delays in disease detection at late metastatic stages. It is of utmost importance to understand the detailed molecular signaling and detect the molecular markers that can be used for the early diagnosis of cancer. Several studies explored the emerging roles of long noncoding RNAs (lncRNAs) in various cancers as well as lung cancer. A long non-coding RNA LINC00273 was recently discovered to promote cancer cell migration and invasion, and its positive correlation with the pathological stages of metastasis may prove it to be a potential target for inhibiting cancer cell metastasis. Comparing real-time expression of LINC00273 in various human clinical cancer tissue samples with normal tissue samples revealed significantly higher expression in cancer tissues. This long intergenic noncoding RNA was found to be highly expressed in human liver tumor-initiating cells, human gastric adenocarcinoma AGS cell line, as well as human non-small cell lung cancer A549 cell line. SiRNA and shRNA-induced knockdown of LINC00273 in both in vitro and in vivo nude mice significantly subsided AGS and A549 cancer cell migration and invasion. LINC00273 knockdown also reduced TGF-β induced SNAIL, SLUG, VIMENTIN, ZEB1 expression, and metastasis in A549 cells. Plenty of reports have suggested the role of microRNAs of the miR200 family in reversing epithelial to mesenchymal transition (EMT) by inhibiting ZEB transcription factors. In this study, hsa-miR-200a-3p was predicted via IntaRNA-Freiburg RNA tools to be a potential target of LINC00273 with a negative free binding energy of −8.793 kcal/mol, and this interaction was verified as a confirmed target of LINC00273 by RNA pulldown, real-time PCR and luciferase assay. Mechanistically, LINC00273 accelerated TGF-β induced EMT by sponging hsa-miR-200a-3p which in turn liberated ZEB1 and promoted prometastatic functions in A549 cells in vitro as verified by real-time PCR and western blotting. The similar expression patterns of these EMT regulatory pathway molecules, viz. LINC00273, hsa-miR-200a-3p, ZEB1 and TGF-β, were also detected in various clinical samples like breast cancer tissues, oral cancer tissues, lung cancer tissues, etc. Overall, this LINC00273 mediated EMT regulatory signaling can serve as a potential therapeutic target for the prevention of lung cancer metastasis.

Keywords: epithelial to mesenchymal transition, long noncoding RNA, microRNA, non-small-cell lung carcinoma

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Authors: Jaci Marie Mastrandrea, Rosario Haro

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Background: The National Comprehensive Cancer Network (NCCN) recommends that healthcare institutions have established processes for integrating palliative care (PC) into cancer treatment and that all cancer patients be screened for PC needs upon initial diagnosis as well as throughout the entire continuum of care (National Comprehensive Cancer Network, 2021). Early PC screening and intervention is directly associated with improved patient outcomes. The Sky Lakes Cancer Treatment Center (SLCTC) is an institution that has access to PC services yet does not have protocols in place for identifying patients with palliative needs or a standardized referral process. The aim of this quality improvement project was to improve early access to PC services by establishing a standardized screening and referral process for outpatient oncology patients. Method: The sample population included all adult patients with an oncology diagnosis who presented to the SLCTC for treatment during the project timeline. The “Palliative and Supportive Needs Assessment'' (PSNA) screening tool was developed from validated, evidence-based PC referral criteria. The tool was initially implemented using paper forms, and data was collected over a period of eight weeks. Patients were screened by nurses on the SLCTC oncology treatment team. Nurses responsible for screening patients received an educational inservice prior to implementation. Patients with a PSNA score of three or higher received an educational handout on the topic of PC and education about PC and symptom management. A score of five or higher indicates that PC referral is strongly recommended, and the patient’s EHR is flagged for the oncology provider to review orders for PC referral. The PSNA tool was approved by Sky Lakes administration for full integration into Epic-Beacon. The project lead collaborated with the Sky Lakes’ information systems team and representatives from Epic on the tool’s aesthetic and functionality within the Epic system. SLCTC nurses and physicians were educated on how to document the PSNA within Epic and where to view results. Results: Prior to the implementation of the PSNA screening tool, the SLCTC had zero referrals to PC in the past year, excluding referrals to hospice. Data was collected from the completed screening assessments of 100 patients under active treatment at the SLCTC. Seventy-three percent of patients met criteria for PC referral with a score greater than or equal to three. Of those patients who met referral criteria, 53.4% (39 patients) were referred for a palliative and supportive care consultation. Patients that were not referred to PC upon meeting criteria were flagged in EPIC for re-screening within one to three months. Patients with lung cancer, chronic hematologic malignancies, breast cancer, and gastrointestinal malignancy most frequently met the criteria for PC referral and scored highest overall on the scale of 0-12. Conclusion: The implementation of a standardized PC screening tool at the SLCTC significantly increased awareness of PC needs among cancer patients in the outpatient setting. Additionally, data derived from this quality improvement project supports the national recommendation for PC to be an integral component of cancer treatment across the entire continuum of care.

Keywords: oncology, palliative and supportive care, symptom management, outpatient oncology, palliative screening tool

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Authors: Loai AbdAllah, Mahmoud Kaiyal

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Missing values in real-world datasets are a common problem. Many algorithms were developed to deal with this problem, most of them replace the missing values with a fixed value that was computed based on the observed values. In our work, we used a distance function based on Bhattacharyya distance to measure the distance between objects with missing values. Bhattacharyya distance, which measures the similarity of two probability distributions. The proposed distance distinguishes between known and unknown values. Where the distance between two known values is the Mahalanobis distance. When, on the other hand, one of them is missing the distance is computed based on the distribution of the known values, for the coordinate that contains the missing value. This method was integrated with Wikaya, a digital health company developing a platform that helps to improve prevention of chronic diseases such as diabetes and cancer. In order for Wikaya’s recommendation system to work distance between users need to be measured. Since there are missing values in the collected data, there is a need to develop a distance function distances between incomplete users profiles. To evaluate the accuracy of the proposed distance function in reflecting the actual similarity between different objects, when some of them contain missing values, we integrated it within the framework of k nearest neighbors (kNN) classifier, since its computation is based only on the similarity between objects. To validate this, we ran the algorithm over diabetes and breast cancer datasets, standard benchmark datasets from the UCI repository. Our experiments show that kNN classifier using our proposed distance function outperforms the kNN using other existing methods.

Keywords: missing values, incomplete data, distance, incomplete diabetes data

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Authors: Vidhula Ahire, Amit Kumar, K. P. Mishra, Gauri Kulkarni

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Herbal polyphenols have gained significance because of their increasing promise in prevention and treatment of cancer. Therefore, development of a dietary compound as an effective radiosensitizer and a radioprotector is highly warranted for cervical cancer patients undergoing therapy. This study describes the cytotoxic effects of the flavonoid, ellagic acid (EA) when administered either alone or in combination with gamma radiation on cervical cancer HeLa cells in vitro. Apoptotic index and proliferation were measured by using trypan blue assay. Reproductive cell death was analyzed by clonogenic assay. Propidium iodide staining for flowcytometry was performed to analyze cell cycle modulation. Nuclear and mitochondrial changes were studied with specific dyes. DNA repair kinetics was analyzed by immunofluorescence assay. Evaluation and comparison of EA effects were performed with other clinically used breast cancer drugs. When tumor cells were exposed to 2 and 4 Gy of irradiation in presence of EA (10 μM), it yielded a synergistic cytotoxic effect on cervical cancer cells whereas in NIH3T3 cells it reversed the injury caused by irradiation and abetted in the regaining of normal healthy cells. At 24h ~25foci/cell was observed and 2.6 fold decrease in the mitochondrial membrane potential. Up to 40% cell were arrested in the G1 phase and 20-36% cells exhibited apoptosis. Our results demonstrate the role of increased apoptosis and cell cycle modulation in the mechanism of EA mediated radiosensitization of cervical cancer cells and thus advocating EA as an adjuvant for preclinical trials in cancer chemo- radiotherapy.

Keywords: cervical cancer, ellagic acid, sensitization, radiation therapy

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Authors: Waqas Ahmad, Eisha Tahir, Shahper Aqeel, Imran Khalid Niazi, Amjad Iqbal

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Background: Breast conservation surgery applies a number of techniques for accurate localization of lesions. Wire localization remains the method of choice in non-palpable breast cancers post-neoadjuvant chemotherapy. Objective: The aim of our study was to determine the accuracy of wire localization procedures in our department and compare it with internationally set protocols as per the Royal College of Radiologists. Post wire mammography, as well as the margin status of the postoperative specimen, assessed the accuracy of the procedure. Methods: We retrospectively reviewed the data of 225 patients who presented to our department from May 2014 to June 2015 post neoadjuvant chemotherapy with non-palpable cancers. These patients are candidates for wire localized lumpectomies either under ultrasound or stereotactic guidance. Metallic marker was placed in all the patients at the time of biopsy. Post wire mammogram was performed in all the patients and the distance of the wire tip from the marker was calculated. The presence or absence of the metallic clip in the postoperative specimen, as well as the marginal status of the postoperative specimen, was noted. Results: 157 sonographic and 68 stereotactic wire localization procedures were performed. 95% of the wire tips were within 1 cm of the metallic marker. Marginal status was negative in 94% of the patients in histopathological specimen. Conclusion: Our audit report declares more than 95% accuracy of image guided wire localization in successful excision of non-palpable breast lesions.

Keywords: breast, cancer, non-palpable, wire localization

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Authors: Sajjad Jafari, Reza Akbari

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Background and Aim: Chrysin, a flavonoid compound found in medicinal plants, honey, and propolis, has potential biological activities that make it an important perspective in the treatment of infectious and cancer diseases. The aim of this review study is to evaluate the biological activities of chrysin in the treatment of infectious and cancer diseases. Material and Methods: The present study is a review study that searched reputable scientific databases such as PubMed, Google Scholar, Scopus, and Web of Science from 2000 to 2023 using keywords such as antimicrobial, antifungal, chrysin, anticancer, antioxidants, and infectious diseases. The researchers examined 25 articles to determine the biological activities of chrysin. Results: Chrysin has high inhibitory or lethal activities on gram-positive and gram-negative bacteria, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Enterococcus faeces. It also has anti-biofilm effects and antifungal effects on strains such as Aspergillus niger and Candida albicans. Chrysin also has anticancer effects on various cancers, including colorectal cancer, pancreatic cancer, breast cancer, and MCF-7 cancer, which have been confirmed in vitro and in vivo. Conclusion: Chrysin has the potential as an important therapeutic option in the treatment of infectious and cancer diseases. Its high antimicrobial and anticancer activities, combined with its low toxicity in nanoparticle form, make it a promising candidate for further clinical trials. The production of anti-microbial and anti-cancer drugs from natural substances, such as chrysin, is a valuable contribution to the field of medicine.

Keywords: chrysin, antimicrobial, anticancer, infectious diseases

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Authors: Itee Chowdhury, Shikha Modi

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Introduction: Cancer is beginning to outpace cardiovascular disease as a cause of death affecting every major organ system with profound implications for perioperative management. Breast cancer is the most common cancer in women in India, accounting for 27% of all cancers. The small changes in analgesic management of cancer patients can greatly improve prognosis and reduce the risk of postsurgical cancer recurrence as opioid-based analgesia has a deleterious effect on cancer outcomes. Shortened postsurgical recovery time facilitates earlier return to intended oncological therapy maximising the chance of successful treatment. Literature reveals that the role of BIS since FDA approval has been assessed in various types of surgeries, but clinical data on its use in oncosurgical patients are scanty. Our study focuses on the role of BIS-guided anaesthesia for breast cancer surgery patients. Methods: A prospective randomized controlled study in patients aged 36-55years scheduled for modified radical mastectomy was conducted in 51 patients in each group who met the inclusion and exclusion criteria, and randomization was done by sealed envelope technique. In BIS guided anaesthesia group (B), sevoflurane was titrated to keep the BIS value 45-60, and thereafter if the patient showed hypertension/tachycardia, an opioid was given. In standard anaesthesia care (group C), sevoflurane was titrated to keep MAC in the range of 0.8-1, and fentanyl was given if the patient showed hypertension/tachycardia. Intraoperative opioid consumption was calculated. Postsurgery recovery characteristics, including Aldrete score, were assessed. Patients were questioned for pain, PONV, and recall of the intraoperative event. A comparison of age, BMI, ASA, recovery characteristics, opioid, and VAS score was made using the non-parametric Mann-Whitney U test. Categorical data like intraoperative awareness of surgery and PONV was studied using the Chi-square test. A comparison of heart rate and MAP was made by an independent sample t-test. #ggplot2 package was used to show the trend of the BIS index for all intraoperative time points for each patient. For a statistical test of significance, the cut-off p-value was set as <0.05. Conclusions: BIS monitoring led to reduced opioid consumption and early recovery from anaesthesia in breast cancer patients undergoing MRM resulting in less postoperative nausea and vomiting and less pain intensity in the immediate postoperative period without any recall of the intraoperative event. Thus, the use of a Bispectral index monitor allows for tailoring of anaesthesia administration with a good outcome.

Keywords: bispectral index, depth of anaesthesia, recovery, opioid consumption

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Authors: Ziyun Li, Jiudi Zhong, June Zhang

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Background: The diagnosis and treatment of lung cancer lead to varying degrees of psychological and social maladjustment among patients with lung cancer. Understanding psychosocial adjustment (PA) and its influencing factors in young and middle-aged lung cancer patients is essential to help them return to society and lead a normal life. Objectives: This study aims to examine the mediating role of resilience in the association between stigma and psychosocial adjustment among young and middle-aged patients with lung cancer. Methods: A total of 235 patients with lung cancer were recruited from a tertiary grade A cancer center in southern China and investigated using a self-designed general information questionnaire, Psychosocial Adjustment to Illness Scale Self-Report, Social Impact Scale, and Conner-Davidson Resilience Scale. Results: The mean score of PA was (32.61±14.75), and its influencing factors included treatment modalities, stigma, and resilience. The total effect of stigma on PA was significant (total effect=0.418, SE=0.045, 95%CI [0.310-0.497]), and a positive indirect effect was identified for stigma on PA via resilience (indirect effect=0.143, SE=0.041, 95% CI [0.075-0.236]). Conclusion: Stigma and resilience are significantly associated with PA, and resilience is also a mediating variable between stigma and PA. This study suggests that individualized interventions can be made to improve the PA by alleviating their stigma, or by enhancing their resilience in young and middle-aged lung cancer patients.

Keywords: psychosocial adjustment, lung cancer, cancer caring, nursing, young and middle-aged

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Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin

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Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.

Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes

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Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: Helen Zhang

Abstract:

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

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

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Authors: Yori Gidron, Laura Caton, Irit Ben-Aharon

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Background: Many patients and even certain clinicians attribute cancer development to psychosocial factors. Yet, empirical data supports more the prognostic role, rather than the etiological role, of psychosocial factors in cancer. Part of the inconsistency may result from not considering possible moderating factors in the etiological role of psychosocial factors. One important candidate moderating factor is the vagal nerve, whose activity is indexed by heart-rate variability (HRV). The vagal nerve may prevent cancer since it reduces inflammation on the one hand, and since it increases anti-tumor immunity on the other hand. This study examined the moderating role of the vagus in the relation between life threatening events (LTE) and cancer development. Method: We re-analyzed data from the Lifelines Dutch longitudinal cohort study of over 150,000 people. The present study included 82,751 adults, who initially were cancer-free. We extracted information on background factors (e.g., age, gender, fat consumption), whether they ever experienced LTE, HRV and cancer diagnosis as reported by patients in annual clinic visits. HRV was derived from brief ECGs. Results: Of the full sample, 1011 people developed cancer during a follow-up. In the full sample, LTE significantly predicted cancer development (R.R = 1.063 p < .01) and HRV significantly predicted a reduced risk of cancer development (R.R = .506 p <.001). Importantly, LTE significantly predicted cancer only when HRV was low (R.R = 1.056, 95% CI: 1.007 - 1.108, p < .05) but not when HRV was high (R.R = 1.014; 95% CI: 0.916 - 1.122, p > 0.05), independent of confounders. Conclusions: To the best of our knowledge, this is the first study showing in a large sample that LTE predict cancer development, and that this occurs only when vagal nerve activity (HRV) is relatively low. These results could result from lack of vagal modulation of inflammation and also from lack of vagal modulation of stress responses. Results are in line with the cancer-protective role of the vagus. HRV needs to be routinely monitored in the population and future intervention trials need to examine whether vagal nerve activation can prevent cancer in people with LTE and with other cancer risk factors.

Keywords: cancer development, life-events, moderation, vagal nerve

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