Genomic characteristics and evolution of Multicentric Esophageal and gastric Cardiac Cancer.

BACKGROUND: Esophageal carcinoma (EC) and gastric cardiac adenocarcinoma (GCA) have high incidence rates in the Chaoshan region of South China. Multifocal esophageal and cardiac cancer (MECC) is commonly observed in this region in clinical practice. However, the genomic characteristics of MECC remains unclear. MATERIALS AND METHODS: In this study, a total of 2123 clinical samples of EC and GCA were analyzed to determine the frequency of multifocal tumors, as well as their occurrence sites and pathological types. Cox proportional hazards regression was used to model the relationship between age, sex, and tumor state concerning survival in our analysis of the cohort of 541 patients with available follow-up data. We performed whole-genome sequencing on 20 tumor foci and 10 normal samples from 10 MECC patients to infer clonal structure on 6 MECC patients to explore genome characteristics. RESULT: The MECC rate of EC and GCA was 5.65% (121 of 2123). Age and sex were potential factors that may influence the risk of MECC (p < 0.001). Furthermore, MECC patients showed worse survival compared with single tumor patients. We found that 12 foci from 6 patients were multicentric origin model (MC), which exhibited significant heterogeneity of variations in paired foci and had an increased number of germline mutations in immune genes compared to metastatic model. In MC cases, different lesions in the same patient were driven by distinct mutation and copy number variation (CNV) events. Although TP53 and other driver mutation genes have a high frequency in the samples, their mutation sites show significant heterogeneity in paired tumor specimens. On the other hand, CNV genes exhibited higher concordance in paired samples, especially in the amplification of oncogenes and the deletion of tumor suppressor genes. CONCLUSIONS: The extent of inter-tumor heterogeneity suggests both monoclonal and polyclonal origins of MECC, which could provide insight into the genome diversity of MECC and guide clinical implementation.

Plasma cell-free DNA as a sensitive biomarker for multi-cancer detection and immunotherapy outcomes prediction.

BACKGROUND: Cell-free DNA (cfDNA) has shown promise in detecting various cancers, but the diagnostic performance of cfDNA end motifs for multiple cancer types requires verification. This study aimed to assess the utility of cfDNA end motifs for multi-cancer detection. METHODS: This study included 206 participants: 106 individuals with cancer, representing 20 cancer types, and 100 healthy individuals. The participants were divided into training and testing cohorts. All plasma cfDNA samples were profiled by whole-genome sequencing. A random forest model was constructed using cfDNA 4 bp-end-motif profiles to predict cancer in the training cohort, and its performance was evaluated in the testing cohort. Additionally, a separate random forest model was developed to predict immunotherapy responses. RESULTS: In the training cohort, the model based on 4 bp-end-motif profiles achieved an AUC of 0.962 (95% CI 0.936-0.987). The AUC in the testing cohort was 0.983 (95% CI 0.960-1.000). The model also maintained excellent predictive ability in different tumor sub-cohorts, including lung cancer (AUC 0.918, 95% CI 0.862-0.974), gastrointestinal cancer (AUC 0.966, 95% CI 0.938-0.993), and other cancer cohort (AUC 0.859, 95% CI 0.776-0.942). Moreover, the model utilizing 4 bp-end-motif profiles exhibited sensitivity in identifying responders to immunotherapy (AUC 0.784, 95% CI 0.609-0.960). CONCLUSION: The model based on 4 bp-end-motif profiles demonstrates superior sensitivity in multi-cancer detection. Detection of 4 bp-end-motif profiles may serve as potential predictive biomarkers for cancer immunotherapy.

Double versus Single Primary Malignant Neoplasm of Breast and Colorectal Cancer: A Case-Control Study.

PURPOSE: Breast cancer (BC) and colorectal cancer (CRC) are common in female. This study compared survival time between women affected with both cancers with ones with single BC or single CRC. METHOD: Medical records of subjects with both BC & CRC (June 1, 2010, to June 30, 2021) were reviewed. Age-matched subjects who had BC or CRC alone were used as control. Survival analysis using Kaplan-Meier method was performed. RESULT: There were 63 double cancers [40 BC first (DBC): 23 CRC first (DCRC), mean age±SD 60.5±9.9 and 60.9±12.2 years] and 76 subjects in single cancer group [53 SBC: 23 SCRC, mean age 57.4±11.3 and 61.1±12.5 years]. The 5-year survival rate of the double cancer group was 74.6% and the single cancer group was 63.2%. D-group had slightly longer survival time than S-group (116.5±4.0 vs. 101.3±5.5, p=0.055). In D-group, the occurrence of addition of other primary cancers were more common (p=0.015). The second cancer occurred 61.7±45.3 months later in DBC group, and 39.1±26.6 months later in DCRC group (p=0.016). SCRC had shorter survival time vs. DCRC group (p=0.031). SBC and DBC had no different in mean survival time. CONCLUSION: BC and CRC could occur as a part of multiple primary cancers. Detection of more than one cancer did not lead to decrease survival if the second cancer was early detected and treated. The occurrence of the second cancer might be beyond 5 years after the diagnosis of the first cancer. Thus, longer surveillance may be warranted. Awareness and provision of early screening should be offered to individuals diagnosed with either primary cancer. Detection of more than one cancer did not lead to shorter survival.

Identification of a TP53 Mutation in a Patient With Li-Fraumeni Syndrome and Not Meeting the Revised Chompret Criteria: A Case Report.

Li-Fraumeni syndrome (LFS) is a rare familial disorder caused by germline TP53 mutations. Despite the establishment of the revised Chompret criteria to guide genetic testing for TP53, identifying LFS in patients who do not satisfy these criteria remains a challenge. Herein, we present the case of a 50-year-old woman with a history of breast, lung, colorectal, and tongue cancers who did not satisfy the revised Chompret criteria. However, genetic testing ultimately revealed a TP53 mutation, leading to the diagnosis of LFS. Although her family history did not satisfy the classic LFS criteria, she had a TP53 core tumor before the age of 46 years. This case highlights the importance of considering LFS in patients with a history of multiple cancers and suggests that genetic testing should be considered even in patients who do not satisfy the revised Chompret criteria.

Impact of previous extra-pulmonary malignancies on surgical outcomes of sequential primary non-small cell lung cancer.

Reduced cancer deaths have led to an increase in the number of cancer survivors and the risk of the second primary tumor. This study explored the surgical outcomes of patients with non-small cell lung cancer as the second primary tumor and the impact of previous extra-pulmonary malignancies. Patients' data were obtained from Surveillance, Epidemiology and End Results database. The patients were divided into lung surgery and non-surgery groups. Propensity-score matching was used to balance potential confounders. Kaplan-Meier curves were generated to test the overall survival and lung-cancer-specific survival. Cox regression analysis was performed to calculate death risk. In total 3054 lung surgery and 1094 non-surgery patients with stage I-II non-small cell lung cancer as the second primary tumor were included. The surgery group showed longer overall survival (68 vs. 22 months) and lung cancer-specific survival (not reached vs. 37 months) than those of non-surgery groups (both P < 0.001). Patients with previous hormone-dependent malignancies had similar survival rates (overall survival: 22 vs. 20 months, P = 0.666; lung cancer-specific survival: 38 vs. 37 months, P = 0.292) as those with non-hormone dependent malignancies in the non-surgery group. Significantly longer overall survival (90 vs. 60 months, P = 0.001) was observed in patients with hormone-dependent malignancies in the surgery group; however, there was no difference in lung cancer-specific survival (P = 0.225). Competing risk analysis showed that for patients undergoing lung surgery, there was higher previous malignancy-induced mortality in patients with non-hormone dependent malignancies than in patients with hormone-dependent malignancies. However, there was no difference in lung cancer-induced mortality between the two groups. Patients who underwent lobectomy showed longer survival than those who underwent pneumonectomy and other resection types (89, 27.5 and 65 months, P < 0.001). In summary, lung surgery is beneficial for patients with stage I-II non-small cell lung cancer as the second primary tumor after hormone-dependent malignancy resection.

Typing of cancer cells by microswimmer based on Co-Fe-MOF for one-step simultaneously detect multiple biomarkers.

Capturing, identifying, and counting CTCs cancer cells that have escaped from the tumor and wandered into the bloodstream is a major challenge. We proposed a noval microswimmer dual-mode aptamer (electrochemical and fluorescent)-(Mapt-EF) homogeneous sensor with active capture/controlled release double signaling molecule/separation and release cell based on the Co-Fe-MOF nanomaterial for simultaneous one-step detection of multiple biomarkers protein tyrosine kinase-7 (PTK7), Epithelial cell adhesion molecule (EpCAM), and mucin-1 (MUC1) for diagnosis of multiple cancer cell types. The Co-Fe-MOF is a nano-enzyme capable of catalyzing the decomposition of hydrogen peroxide to release bubbles of oxygen, producing a driving force to conduct hydrogen peroxide through the liquid, and has the capacity to self-decompose during the catalytic process. Phosphoric acid is present in the aptamer chains of PTK7, EpCAM, and MUC1, and the aptamer chains are adsorbed to the surface of the Mapt-EF homogeneous sensor in the form of a gated switch to inhibit the catalytic decomposition activity of hydrogen peroxide. The Mapt-EF homogeneous sensor has the capability to actively target biomarkers that can be entrained by oxygen bubbles without being degraded. The detection time of the sensor was 20 min, the detection limits were 9.6 fg/mL, 8.4 fg/mL and 7.7 fg/mL with the linear range was 0-20 pg/mL, respectively. The Mapt-EF homogeneous sensor has high detection sensitivity, and its detection limit can reach the level of single cell at the lowest. The Mapt-EF homogeneous sensor has great application potential in clinical detection and analysis of tumor cells.

Risks of second non-breast primaries following breast cancer in women: a systematic review and meta-analysis.

BACKGROUND: Second primary cancer incidence is rising among breast cancer survivors. We examined the risks of non-breast second primaries, in combination and at specific cancer sites, through a systematic review and meta-analysis. METHODS: We conducted a systematic search of PubMed, Embase, and Web of Science, seeking studies published by March 2022. We included studies that reported standardized incidence ratios (SIRs), with associated standard errors, assessing the combined risk of second non-breast primaries following breast cancer. We performed meta-analyses of combined second primary risks, stratifying by age, follow-up duration, and geographic region. We also assessed second primary risks at several specific sites, stratifying by age. The inverse variance method with DerSimonian-Laird estimators was used in all meta-analyses, assuming a random-effects model. Associated biases and study quality were evaluated using the Newcastle-Ottawa scale. RESULTS: One prospective and twenty-seven retrospective cohort studies were identified. SIRs for second non-breast primaries combined ranged from 0.84 to 1.84. The summary SIR estimate was 1.24 (95% CI 1.14-1.36, I2: 99%). This varied by age: the estimate was 1.59 (95% CI 1.36-1.85) when breast cancer was diagnosed before age 50, which was significantly higher than in women first diagnosed at 50 or over (SIR: 1.13, 95% CI 1.01-1.36, p for difference: < 0.001). SPC risks were also significantly higher when based on Asian, rather than European, registries (Asia-SIR: 1.47, 95% CI 1.29-1.67. Europe-SIR: 1.16, 95% CI 1.04-1.28). There were significantly increased risks of second thyroid (SIR: 1.89, 95% CI 1.49-2.38), corpus uteri (SIR: 1.84, 95% CI 1.53-2.23), ovary (SIR: 1.53, 95% CI 1.35-1.73), kidney (SIR: 1.43, 95% CI 1.17-1.73), oesophagus (SIR: 1.39, 95% CI 1.26-1.55), skin (melanoma) (SIR: 1.34, 95% CI 1.18-1.52), blood (leukaemia) (SIR: 1.30, 95% CI 1.17-1.45), lung (SIR: 1.25, 95% CI 1.03-1.51), stomach (SIR: 1.23, 95% CI 1.12-1.36) and bladder (SIR: 1.15, 95% CI 1.05-1.26) primaries. CONCLUSIONS: Breast cancer survivors are at significantly increased risk of second primaries at many sites. Risks are higher for those diagnosed with breast cancer before age 50 and in Asian breast cancer survivors compared to European breast cancer survivors. This study is limited by a lack of data on potentially confounding variables. The conclusions may inform clinical management decisions following breast cancer, although specific clinical recommendations lie outside the scope of this review.

Thyroid and renal cancers: A bidirectional association.

There is a deep interrelation between the thyroid gland and the kidney parenchyma, with dysfunction of the first leading to significant changes in renal metabolism and vice versa. Given the recognition of cancer as a systemic disease, the raise of thyroid tumors and the common association of several malignancies, such as breast cancer, prostate cancer, colorectal cancer, and other, with an increased risk of kidney disease, public health alert for these conditions is warranted. A systematic review of the current evidence on the bidirectional relationship between thyroid and renal cancers was conducted including 18 studies, highlighting patient's characteristics, histology, time for secondary malignancy to develop from the first diagnosis, treatment, and follow-up. A total of 776 patients were identified; median age was 64 years (range: 7-76 years). Obesity and family history were identified as the most common risk factors, and genetic susceptibility was suggested with a potential strong association with Cowden syndrome. Controversy on chemo and radiotherapy effects was found, as not all patients were previously exposed to these treatments. Men were more likely to develop kidney cancer after a primary thyroid malignancy, with 423/776 (54%) experiencing renal disease secondarily. Median time after the first malignancy was 5.2 years (range: 0-20 years). With the advancement of current oncological therapy, the prognosis for thyroid cancer patients has improved, although there has been a corresponding rise in the incidence of multiple secondary malignancy within the same population, particularly concerning the kidney. Surgery can achieve disease-free survival, if surveillance follow-up allows for an early localized form, where radical treatment is recommended.

Multiple cancer type classification by small RNA expression profiles with plasma samples from multiple facilities.

Liquid biopsy is expected to be a promising cancer screening method because of its low invasiveness and the possibility of detecting multiple types in a single test. In the last decade, many studies on cancer detection using small RNAs in blood have been reported. To put small RNA tests into practical use as a multiple cancer type screening test, it is necessary to develop a method that can be applied to multiple facilities. We collected samples of eight cancer types and healthy controls from 20 facilities to evaluate the performance of cancer type classification. A total of 2,475 cancer samples and 496 healthy control samples were collected using a standardized protocol. After obtaining a small RNA expression profile, we constructed a classification model and evaluated its performance. First, we investigated the classification performance using samples from five single facilities. Each model showed areas under the receiver curve (AUC) ranging from 0.67 to 0.89. Second, we performed principal component analysis (PCA) to examine the characteristics of the facilities. The degree of hemolysis and the data acquisition period affected the expression profiles. Finally, we constructed the classification model by reducing the influence of these factors, and its performance had an AUC of 0.76. The results reveal that small RNA can be used for the classification of cancer types in samples from a single facility. However, interfacility biases will affect the classification of samples from multiple facilities. These findings will provide important insights to improve the performance of multiple cancer type classifications using small RNA expression profiles acquired from multiple facilities.

Long-Term patterns of cancer incidence among patients with and without type 2 diabetes in the United Kingdom.

AIMS: Studies using contemporary cohorts are needed to assess the association between type 2 diabetes and cancer. METHODS: Using the United Kingdom Clinical Practice Research Datalink, we matched patients with type 2 diabetes between 1988 and 2019 to patients without type 2 diabetes. Poisson regression models were fit to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for cancer. In secondary analyses, we determined whether the strength of the association varied with calendar time and whether patients with type 2 diabetes had a higher incidence of being diagnosed with multiple cancers during the follow-up period. RESULTS: 890,214 patients with type 2 diabetes were matched to an equal number of patients without type 2 diabetes. Patients with type 2 diabetes had a higher cancer incidence than patients without type 2 diabetes (IRR 1.19, 95% CI 1.18-1.21). The IRR was higher 2010 onwards (IRR: 1.25, 95% CI: 1.23-1.28) compared with the association in previous years. Overall, patients with type 2 diabetes had a 5% higher incidence of being diagnosed with multiple cancers (IRR: 1.05, 95% CI: 1.04-1.07). CONCLUSIONS: The results of this large population-based study indicate that type 2 diabetes is associated with an increased risk of several cancers.

Triple cancer of gallbladder, common bile duct and papilla of Vater: Report of a case and review of literature.

INTRODUCTION AND IMPORTANCE: Synchronous malignancies of gallbladder and biliary tree are together rare entity whose pathogenesis is yet unknown. We report the case of a triple synchronous cancer of 3 distinct location: gallbladder, common bile duct (CBD) and papilla of Vater. CASE PRESENTATION: An 84-years-old woman, was admitted to our Hospital with clinics features of obstructive jaundice. Dilatation of the biliary tree and CBD without evidence of gallstones was seen at US. CT scan confirmed distal CBD obstruction. An endo-US showed a nodule of the head of pancreas infiltrating the lower CBD. Finally, hepatic-MRI displayed a gallbladder malignancy with invasion of CBD. Preoperative staging showed 3 diagnostic suspicions: carcinoma of CBD on CT, pancreatic carcinoma on endo-US and malignancy of gallbladder on MRI. A cephalic duodenopancreatectomy and radical gallbladder resection was performed. Final pathology revealed 3 distinct location of moderately differentiated adenocarcinomas: Gallbladder, CBD and Vater's papilla. Microscopic examination didn't detect any direct continuity between the 3 tumors. Metastases were identified in the pancreaticoduodenal, peri-hepatic and peri-gastric lymph nodes. CLINICAL DISCUSSION: Literature displayed 22 cases of synchronous malignancies of gallbladder and CBD and 1 case of triple cancer with associated Vater's papilla carcinoma. In most of these cases, an association with an anomalous pancreatic-bile duct junction was reported. Although the real incidence remain unknown, it was reported to occur in 5-10% of CBD cancers. CONCLUSION: Suspicion of such combination of cancer should be remembered, especially when preoperative investigations don't allow a precise localization of tumor in the biliary tree.

Comprehensive analyses of PBRM1 in multiple cancer types and its association with clinical response to immunotherapy and immune infiltrates.

BACKGROUND: The prognostic value of polybromo 1 (PBRM1) gene mutations in clear cell renal carcinoma (CCRCC) with anti-programmed death-ligand 1 (PD-L1) therapy remains controversial, and few studies have reported the impact of PBRM1 mutations in other cancer types. METHODS: The patient information was obtained from cBioPortal and the Tumor Immune Estimation Resource (TIMER) databases. Mann-Whitney U test were used for correlation analysis. For survival analyses, Kaplan-Meier survival curves were used and compared using the log-rank test. Cox's regression model was used to perform univariable and multivariable analyses. RESULTS: Our study, for the first time, performed comprehensive analyses of PBRM1 mutation frequency, PBRM1 expression, relationship of PBRM1 mutations with clinical benefit from immunotherapy, and PBRM1 expression with immune infiltrates in diverse cancer types. The results showed that the expression of PBRM1 was significantly lower in diverse cancer types compared with normal tissues. Based on multivariable analysis, PBRM1 mutations trended towards worse clinical outcomes from anti-PD-L1 in CCRCC, lung adenocarcinoma (LUAD), bladder urothelial carcinoma (BLCA), and skin cutaneous melanoma (SKCM), and a significant association was observed in LUAD and BLCA. PBRM1 mutations were associated with higher TMB in diverse cancer types and significant associations were observed in LUAD and BLCA. The expression of PBRM1 was found to positively correlate with immune infiltrates in diverse cancer types. CONCLUSIONS: Our findings suggested caution in starting immunotherapy alone in PBRM1 mutant patients. Further studies are needed to improve treatment for PBRM1 mutant patients.

[Two Cases of Synchronous Double Primary Prostate Cancer Accompanying Bone Metastasis and Colon Cancer].

We report two cases of synchronous double primary cancers, which were composed of prostate cancer accompanied by bone metastasis and colon cancer, within only five months of each other. The first was a 77-year-old man whose ECOG PS was 0. He was referred to our hospital in March 2020 because abdominal CT scan, which was performed at a clinic for the purpose of close examination of poor control of diabetes, showed wall thickening of the sigmoid colon. A further examination revealed prostate cancer accompanied by metastatic bone cancer and sigmoid colon cancer. Laparoscopic sigmoid colectomy was performed in April. Currently, six months after the surgery, both the prostate cancer and its accompanying metastatic bone cancer are well controlled by hormonal therapy. The second case was an 86-year-old man with an ECOG PS of 3 who was brought to our hospital by ambulance in August, 2020 because of fever and abdominal pain. A close examination revealed cecal cancer accompanying acute appendicitis. Prostate cancer accompanied by metastatic bone cancer was also diagnosed. Laparoscopic ileocecal resection was performed in the same month, but, unfortunately, the patient had repeated aspiration pneumonia and he finally passed away 43 days after surgery. We discuss the treatment strategy for colorectal cancer with synchronous or metachronous prostate cancer, which has been increasing in recent years, and include epidemiological considerations.

Evaluation of Pharyngeal Background Mucosa in Patients with Superficial Hypopharyngeal Carcinoma.

OBJECTIVES/HYPOTHESIS: Transoral surgery (TOS) has become increasingly popular for patients with superficial hypopharyngeal squamous cell carcinoma (SCC). However, the number of patients in whom metachronous multiple SCC of the head and neck (HNSCC) occurs has also increased. In this study, we investigated whether multiple lugol-voiding lesions (LVLs) in the pharyngeal background mucosa observed during TOS would be a biomarker of metachronous HNSCC. STUDY DESIGN: Retrospective study. METHODS: We examined 362 patients who underwent TOS for superficial hypopharyngeal carcinoma. Endoscopic images were reviewed in a blinded fashion by two endoscopists. LVLs in the pharyngeal mucosa were graded as follows: A, no lesions; B, 1 to 4 lesions; and C, ≥5 lesions per endoscopic view. RESULTS: Cumulative incidence curves of secondary HNSCC in the groups of grades A, B, and C revealed 3-year incidence rates of 14.4%, 18.8%, and 29.3%, respectively (P = .001 for A vs. C and P = .002 for B vs. C). Cumulative incidence curves of third HNSCC in the groups of grades A, B. and C revealed 5-year incidence rates of 3.9%, 9.8%, and 19.6%, respectively (P = .001 for A vs. C and P = .006 for B vs. C). Cumulative incidence curves of fourth HNSCC in the groups of grades A, B, and C revealed 7-year incidence rates of 0%, 2.3%, and 13.2%, respectively (P = .025 for A vs. C and P = .009 for B vs. C). CONCLUSIONS: Multiple LVLs in the pharyngeal mucosa increase the risk of development of metachronous multiple HNSCC. LEVEL OF EVIDENCE: 3 (nonrandomized, controlled cohort/follow-up study) Laryngoscope, 131:2036-2040, 2021.

Risk Factors of Synchronous Breast and Thyroid Cancer: a Controlled Multicenter Study and Review of the Literature.

BACKGROUND: Breast cancer (BC) is one of the most common cancers diagnosed in women in the United States. Thyroid cancer (TC) is also one of the fastest increasing cancer types in the United States, with most cases being papillary thyroid carcinomas. OBJECTIVE: To identify possible risk factors for the synchronous or metachronous co-occurrence of breast and thyroid cancers. METHODS: We carried out a study, which consisted of data from four gynecological clinics: two in Greece (Athens, Alexandroupolis, Ioannina) and one in Germany, collected from June 2017 to June 2020. The patients were divided into two groups: the first group consisted of 58 patients with breast cancer and a personal history of thyroid cancer. The second group (control group) included 50 patients with the same characteristics as to age, parity, type of pregnancy, treatment for sterility, polycystic ovaries, regularity of the menstrual cycle, breast density, BMI, family history of cancer, blood group rhesus and histological results of breast cancer. The data we collected were analyzed using version 20 of the SPSS statistical package. The Chi-square test was used for statistical analysis and a p-value<0.005 was considered statistically significant. RESULTS: The only factors that seem to be related with the association of breast and thyroid cancer were: history of abortion and multiparity. CONCLUSION: In our study there is a higher chance of developing breast cancer after diagnosing thyroid cancer and vice versa. More than genetic mutations, a possible hormonal pathway of these two malignancies is possible. The hormonal change in women who had many children or abortions could be a risk factor to develop both cancers. More studies are necessary to confirm our findings.

Oral squamous cell carcinoma of the tongue dorsum with multiple cancer-associated mutations in the TP53 gene.

OBJECTIVES: Squamous cell carcinoma (SCC) of the tongue is one of the most common oral cancers, tongue dorsum being a site of low incidence of primary SCC. We report a rare case of SCC of the tongue dorsum in a 69-year-old man having a history of multiple cancers, including esophageal cancer, gastric cancer, and renal cell carcinoma. We discuss the findings in relation to past reports. MATERIALS AND METHODS: TP53 was PCR amplified using the genomic DNA extracted from peripheral blood mononuclear cells and formalin-fixed, paraffin-embedded tissue sections from the tumor site of the patient, and was sequenced. RESULTS: Physical examination revealed an elastic hard mass on the tongue dorsum, with a size of 22 × 15 mm. There were no palpable enlarged lymph nodes in the cervical and submandibular region. An incisional biopsy was performed. The diagnosis was well-differentiated SCC of tongue, T2N0M0, Stage II, and was treated through surgery. Surgical specimen of the deep ulcer area showed increased expression of p16 protein with no expression of p53 protein. He had a heterozygous gene polymorphism (c.215C > G: p.Pro72Arg) and a germline mutation (c.838A > T: p.Arg280*) of the TP53. However, there has been no recurrence or metastasis of the tongue carcinoma through the follow-up for 3 years. CONCLUSION: Germline TP53 mutation and codon 72 polymorphism are risk factors for uncontrolled cell proliferation, possibly leading to the patient's clinical phenotype. Therefore, strict follow-up is required when treating those who are at a higher risk of cancer due to a TP53 mutation.

Thymoquinone, an Active Compound of Nigella sativa: Role in Prevention and Treatment of Cancer.

BACKGROUND: Cancer is the leading cause of death worldwide and the current mode of cancer treatment causes side effects on normal cells and are still the key challenges in its' treatment. However, natural products or active compounds of medicinal plants have shown to be safe, affordable, and effective in diseases cure. METHODS: In this context, scientific studies evidence the health-promoting effects of natural products, which work through its anti-oxidant, anti-inflammatory, and anti-cancer activity. Thymoquinone (TM), a predominant active compound of Nigella sativa, has confirmed anti-neoplastic activity through its ability to regulate various genetic pathways. In addition, thymoquinone has established anti-cancerous effects through killing of various cancerous cells,and inhibiting the initiation, migration, invasion, and progression of the cancer. The anti-cancer effects of TM are chiefly mediated via regulating various cell signaling pathways such as VEGF, bcl2/bax ratio, p53, NF-kB, and oncogenes. RESULTS: The anti-cancer drugs have limitations in efficacy and also causes adverse side effects on normal cells. The combination of anti-cancer drugs and thymoquinone improves the efficacy of drugs which is evident by decrease resistance to drugs and regulation of various cell signaling pathways. Moreover, combination of anti-cancer drugs as well as thymoquinone shows synergistic effect on killing of cancer cells and cells viability. Thus, TM, in combination with anti-cancer drugs, can be a good strategy in the management of various types of cancer. CONCLUSION: In this review article, we deliver an outline of thymoquinone role in cancer inhibition and prevention of cancer-based on in vivo and in vitro studies. Further studies on thymoquinone based on clinical trials are highly required to explore the benefits of thymoquinone in cancer management.

Targeting delivery of partial VAR2CSA peptide guided N-2-Hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles for multiple cancer types.

To developing a multiple cancer types targeting drug delivery carrier system, a 28 amino acids from the VAR2CSA was synthesized as the placental CSA-binding peptide (plCSA-BP). Its specific binding ability to cancer cells was tested on cancer tissue array, and the results showed that plCSA-BP could bind to multiple cancer types. Then, the plCSA-BP was used as a guiding peptide to coat nanoparticles synthesized from N-2-HACC (CSA/HACC-NPs) which were loaded with prodigiosin (CSA/HACC-PNPs) or indocyanine green (CSA/HACC-INPs). The cancer cells specific targeting and efficacy of the CSA/HACC-PNPs were tested by different cancer cells in vitro and various cancer xenograft model in vivo. A scramble peptide (SCR) was used as control and synthesized SCR/HACC-PNPs and SCR/HACC-INPs. The results showed that the CSA/HACC-INPs could specifically uptake by JEG-3, PC3 and A594 cells, and the CSA/HACC-PNPs exhibited better anti-cancer activity and lower toxic effect in subcutaneous choriocarcinoma and prostatic tumor models compared with the free prodigiosin, HACC-PNPs and SCR/HACC-PNPs. So, the CSA/HACC-NPs could be used as a specific delivery carrier for multiple cancer types, and provided an alternate treatment option of various cancers with a single recipe.

Integrative Analysis of Cancer Omics Data for Prognosis Modeling.

Prognosis modeling plays an important role in cancer studies. With the development of omics profiling, extensive research has been conducted to search for prognostic markers for various cancer types. However, many of the existing studies share a common limitation by only focusing on a single cancer type and suffering from a lack of sufficient information. With potential molecular similarity across cancer types, one cancer type may contain information useful for the analysis of other types. The integration of multiple cancer types may facilitate information borrowing so as to more comprehensively and more accurately describe prognosis. In this study, we conduct marginal and joint integrative analysis of multiple cancer types, effectively introducing integration in the discovery process. For accommodating high dimensionality and identifying relevant markers, we adopt the advanced penalization technique which has a solid statistical ground. Gene expression data on nine cancer types from The Cancer Genome Atlas (TCGA) are analyzed, leading to biologically sensible findings that are different from the alternatives. Overall, this study provides a novel venue for cancer prognosis modeling by integrating multiple cancer types.

Every distant deposit is not a metastasis: Synchronous primaries do exist.

BACKGROUND: Synchronous occurrence of two malignant tumors is a rare event. With increasing use of sophisticated imaging modalities for staging, synchronous multiple tumors are more commonly detected now. Assuming the second primary malignancy as metastasis will change the intent of treatment from curative to palliative, greater awareness among oncologists is of paramount importance. This study is an example where thorough clinical examination and proper judgment resulted in correct diagnosis and appropriate treatment. MATERIALS AND METHODS: This is a prospective descriptive study. Patients diagnosed with synchronous primary tumors from January 2016 to November 2017 at our center were reviewed. RESULTS: Ten cases of synchronous primary malignancies were detected during this period. A total of 20 primary tumors were diagnosed. Lung carcinoma and gastrointestinal malignancies were the most common (five patients each). The median age was 59.5 years. Seven patients were male. Second primary tumor was suspected in four patients during clinical examination, while in six patients it was suspected on imaging. Even in the presence of two primary tumors, three patients were treated with curative intent. CONCLUSION: Possibility of synchronous second primary malignancy should always be kept whenever a distant deposit is detected at an unusual site. Histopathological evaluation of the lesion before assuming a metastasis will lead to accurate diagnosis, staging, and appropriate treatment.