Malignant pleural mesothelioma:The disdained member of thoracic oncology!

Pleural mesothelioma is a very aggressive malignancy that arises from the pleural mesothelial cell lining and is linked strongly to prior asbestos exposure.The ban on asbestos has helped to lower the incidence,but in developing countries like India,it is expected to rise.It has an extended latency period usually progressing over decades and presents with nonspecific symptoms.It has a median survival ranging between 10-22 months.The diagnosis of malignant pleural mesothelioma is challenging and is done using computed tomography(CT),magnetic resonance imaging,or positron emission tomography-CT,with the last two predicting the resectability of the tumor better than CT alone.A pleural biopsy along with an array of immunohistochemical markers,such as p16,BRCA1 associated protein 1,and claudin-4,are required for a definitive diagnosis.Several genetic alterations have prognostic significance as well.The current histological subtype identification is indispensable for decision making because of the new therapeutic avenues being explored.The combination of nivolumab and ipilimumab-based immunotherapy outperformed platinum and pemetrexed-based chemotherapy in terms of survival benefit and improved quality of life especially for non-epithelioid subtypes.However,the latter continues to be a robust treatment option for patients with the epithelioid subtype.Surgery is recommended for resectable cases with radiotherapy being indicated in neoadjuvant,adjuvant,and palliative settings along with systemic treatment.This review article provides an overview of epidemiology,etiology,clinical manifestations,diagnostic approaches(including immunohistochemical and genetic markers),staging,and multidisciplinary approaches to current treatment for malignant pleural mesothelioma using surgery,chemotherapy,immunotherapy,and radiotherapy.It also sheds light on some recent studies(EMPHACIS,CALGB30901,Checkmate-743,etc.)that have led to significant developments in recent years with clinically meaningful results.

Prognostic value and predictive model of tumor markers in stageⅠtoⅢgastric cancer patients

BACKGROUND Preoperative serum tumor markers have been widely used in the diagnosis and treatment of gastric cancer patients.However,few studies have evaluated the prognosis of gastric cancer patients by establishing statistical models with multiple serum tumor indicators.AIM To explore the prognostic value and predictive model of tumor markers in stage I and III gastric cancer patients.METHODS From October 2018 to April 2020,a total of 1236 patients with stage I to III gastric cancer after surgery were included in our study.The relationship between serum tumor markers and clinical and pathological data were analyzed.We established a statistical model to predict the prognosis of gastric cancer based on the results of COX regression analysis.Overall survival(OS)was also compared across different stages of gastric cancer.RESULTS The deadline for follow-up was May 31,2023.A total of 1236 patients were included in our study.Univariate analysis found that age,clinical stage,T and N stage,tumor location,differentiation,Borrmann type,size,and four serum tumor markers were prognostic factors of OS(P<0.05).It was shown that clinical stage,tumor size,alpha foetoprotein,carcinoembryonic antigen,CA125 and CA19-9(P<0.05)were independent prognostic factors for OS.According to the scoring results obtained from the statistical model,we found that patients with high scores had poorer survival time(P<0.05).Furthermore,in stage I patients,the 3-year OS for scores 0-3 ranged from 96.85%,95%,85%,and 80%.In stage II patients,the 3-year OS for scores 0-4 were 88.6%,76.5%,90.5%,65.5%and 60%.For stage III patients,3-year OS for scores 0-6 were 70.9%,68.3%,64.1%,50.9%,38.4%,18.5%and 5.2%.We also analyzed the mean survival of patients with different scores.For stage I patients,the mean OS was 55.980 months.In stage II,the mean OS was 51.550 months.The mean OS for stage III was 39.422 months.CONCLUSION Our statistical model can effectively predict the prognosis of gastric cancer patients.

Long-term outcomes of a phase Ⅱ randomized controlled trial comparing intensity-modulated radiotherapy with or without weekly cisplatin for the treatment of locally recurrent nasopharyngeal carcinoma

Background:Salvage treatment for locally recurrent nasopharyngeal carcinoma(NPC) is complicated and relatively limited.Radiotherapy,combined with effective concomitant chemotherapy,may improve clinical treatment outcomes.We conducted a phase Ⅱ randomized controlled trial to evaluate the efficacy of intensity-modulated radiotherapy with concomitant weekly cisplatin on locally recurrent NPC.Methods:Between April 2002 and January 2008,69 patients diagnosed with non-metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group(n = 34) or radiotherapy alone group(n = 35).All patients received intensity-modulated radiotherapy.The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days(range 23-53 days).The concomitant chemotherapy schedule was cisplatin 30 mg/m^2 by intravenous infusion weekly during radiotherapy.Results:The median follow-up period of all patients was 35 months(range 2-112 months).Between concomitant chemoradiotherapy and radiotherapy groups,there was only significant difference in the 3-year and 5-year overall survival(OS) rates(68.7%vs.42.2%,P = 0.016 and 41.8%vs.27.5%,P = 0.049,respectively).Subgroup analysis showed that concomitant chemoradiotherapy significantly improved the 5-year OS rate especially for patients in stage rT3-4(33.0%vs.13.2%,P = 0.009),stages Ⅲ-Ⅳ(34.3%vs.13.2%,P = 0.006),recurrence interval >30 months(49.0%vs.20.6%,P = 0.017),and tumor volume >26 cm^3(37.6%vs.0%,P = 0.006).Conclusion:Compared with radiotherapy alone,concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC,especially those with advanced T category(rT3-4) and stage(lll-IV) diseases,recurrence intervals >30 months,and tumor volume >26 cm^3.

Nomogram established using risk factors of early gastric cancer for predicting the lymph node metastasis

BACKGROUND For the prognosis of patients with early gastric cancer(EGC),lymph node metastasis(LNM)plays a crucial role.A thorough and precise evaluation of the patient for LNM is now required.AIM To determine the factors influencing LNM and to construct a prediction model of LNM for EGC patients.METHODS Clinical information and pathology data of 2217 EGC patients downloaded from the Surveillance,Epidemiology,and End Results database were collected and analyzed.Based on a 7:3 ratio,1550 people were categorized into training sets and 667 people were assigned to testing sets,randomly.Based on the factors influencing LNM determined by the training sets,the nomogram was drawn and verified.RESULTS Based on multivariate analysis,age at diagnosis,histology type,grade,T-stage,and size were risk factors of LNM for EGC.Besides,nomogram was drawn to predict the risk of LNM for EGC patients.Among the categorical variables,the effect of grade(well,moderate,and poor)was the most significant prognosis factor.For training sets and testing sets,respectively,area under the receiver-operating characteristic curve of nomograms were 0.751[95%confidence interval(CI):0.721-0.782]and 0.786(95%CI:0.742-0.830).In addition,the calibration curves showed that the prediction model of LNM had good consistency.CONCLUSION Age at diagnosis,histology type,grade,T-stage,and tumor size were independent variables for LNM in EGC.Based on the above risk factors,prediction model may offer some guiding implications for the choice of subsequent therapeutic approaches for EGC.

Understanding the multifaceted etiopathogenesis of foot complications in individuals with diabetes

Diabetes mellitus,a chronic disease of metabolism,is characterized by a disordered production or cellular utilization of insulin.Diabetic foot disease,which comprises the spectrum of infection,ulceration,and gangrene,is one of the most severe complications of diabetes and is the most common cause of hospitalization in diabetic patients.The aim of this study is to provide an evidence-based overview of diabetic foot complications.Due to neuropathy,diabetic foot infections can occur in the form of ulcers and minor skin lesions.In patients with diabetic foot ulcers,ischemia and infection are the main causes of non-healing ulcers and amputations.Hyperglycemia compromises the immune system of individuals with diabetes,leading to persistent inflammation and delayed wound healing.In addition,the treatment of diabetic foot infections is challenging due to difficulty in accurate identification of pathogenic microorganisms and the widespread issue of antimicrobial resistance.As a further complicating factor,the warning signs and symptoms of diabetic foot problems can easily be overlooked.Issues associated with diabetic foot complications include peripheral arterial disease and osteomyelitis;accordingly,the risk of these complications in people with diabetes should be assessed annually.Although antimicrobial agents represent the mainstay of treatment for diabetic foot infections,if peripheral arterial disease is present,revascularization should be considered to prevent limb amputation.A multidisciplinary approach to the prevention,diagnosis,and treatment of diabetic patients,including those with foot ulcers,is of the utmost importance to reduce the cost of treatment and avoid major adverse consequences such as amputation.

Stereotactic ablative body radiotherapy for oligometastatic inguinal lymph node in castrate resistant prostate cancer

Dear Editor,Introduction of prostate-specific membrane antigen positron-emission tomography/contrast-enhanced computed tomography(PSMA PET/CECT)for prostate cancer staging and follow-up have increased detection of metastases even in non-regional nodes,often in oligometastatic or oligorecurrent state[1].Some of these merit metastases-directed therapy(MDT)such as surgery or radiotherapy(RT)with curative intent.

Comparative study of CEA and CA19-9 in esophageal,gastric and colon cancers individually and in combination(ROC curve analysis)

Objective： To determine the clinical serum levels of carcinoembryonic antigen （CEA） and carbohydrate antigen 19-9 （CA19-9）, individually and in combination, for the diagnosis of 50 healthy subjects and 150 cases of esophageal, gastric, and colon cancers. Methods： The sensitivities of the two markers were compared individually and in combination, with specificity set at 100%. Receiver operating characteristic （ROC） curves were plotted. Results： Serum CEA levels were significantly higher in cancer patients than in the control group. The sensitivity of CEA was determined： in esophageal cancer, sensitivity=28%, negative predictive value （NPV）=61.72%, and AUC=0.742 （SE=0.05）, with a significance level of P〈0.0001; in gastric cancer, sensitivity=30%, NPV=58.82%, and AUC=0.734 （SE=0.0S）, with a significance level of P〈0.0001; in colon cancer, sensitivity=74%, NPV=79.36%, and AUC=0.856 （SE=0.04）, with a significance level of P〈0.0001. The sensitivity of CA19-9 was also evaluated： in esophageal cancer, sensitivity=18%, NPV=54.94%, and AUC=0.573 （SE=0.05）, with a significance level of P=0.2054. In gastric cancer, sensitivity=42%, NPV=63.29%, and AUC=0.679 （SE=0.05）, with a significance level of P〈0.0011. In colon cancer, sensitivity=26%, NPV=57.47%, and AUC=0.S80 （SE=0.05）, with a significance level ofP=0.1670. The following were the sensitivities of CEA/CA19-9 combined： in esophageal cancer, sensitivity=42%, NPV=63.29%, SE=0.078 （95% CI： 0.0159-0.322）; gastric cancer, sensitivity=S8%, NPV=70.42%, SE=0.072 （9$% CI： -0.0866-0.198）; and colon cancer, sensitivity=72%, NPV=78.12%, SE=0.070 （9S% CI： 0.137-0.415）. Conclusion： CEA exhibited the highest sensitivity for colon cancer, and CA19-9 exhibited the highest sensitivity for gastric cancer. Combined analysis indicated an increase in diagnostic sensitivity in esophageal and gastric cancer compared with that in colon cancer.

A phase Ⅱ study of gemcitabine and carboplatin combination chemotherapy in gallbladder carcinoma

BACKGROUND: Patients with carcinoma of the gallbladder have advanced, unresectable tumor at the time of presentation and face a dismal prognosis in the absence of a standard palliative chemotherapy regimen. This study was undertaken to evaluate the efficacy and safety of combined chemotherapy of gemcitabine and carboplatin in 20 patients with advanced gallbladder carcinoma. METHODS: The criteria of eligibility included chemonaive patients with unresectable gallbladder cancer, bidimensionaIly measurable disease, Zubrod's performance status≤2, and adequate major organ function. The patients received gemcitabine (1000 mg/m^2) on days 1 and 8, and carboplatin (target AUC of 5.0 mg/ml) on day 1, in a 21-day cycle. CT was used for response assessment. RESULTS: In this group of 20 patients with advanced gallbladder carcinoma 6 were men and 14 women, with a median age of 55 years. The stage of the tumor at presentation was IVB in 14 patients (70%), IVA in 3 (15%) and Ⅲ in 3 (15%). Four patients (21%) achieved a complete response, and 3 (15.7%), a partial response; an overall response rate was 36.7%. The median time to progression of the tumor was 33.8 weeks, and 1-year survival rate of the patients was 43.3%. Anemia of WHO grade Ⅲ or Ⅳ was seen in 2 patients (10%) and 1 patient (5%), respectively. Grade Ⅲ neutropenia and thrombocytopenia were observed in 2 patients (10%) and 1 patient (5%), respectively. CONCLUSION: With mild toxicity, combined chemotherapy of gemcitabine and carhoplatin is effective in the treatment of advanced gallbladder carcinoma.

Inhibition of IKK-NFκB pathway sensitizes lung cancer cell lines to radiation

Objective:Cancer cell radioresistance is a stumbling block in radiation therapy.The activity in the nuclear factor kappa B(NFκB)pathway correlates with anti-apoptotic mechanisms and increased radioresistance.The IKK complex plays a major role in NFκB activation upon numerous signals.In this study,we examined the interaction between ionizing radiation(IR)and different members of the IKK-NFκB pathway,as well as upstream activators,RAF1,ERK,and AKT1.Methods:The effect of 4 Gy of IR on the expression of the RAF1-ERK-IKK-NFκB pathway was examined in A549 and H1299 lung cancer cell lines using Western blot analysis and confocal microscopy.We examined changes in radiation sensitivity using gene silencing or pharmacological inhibitors of ERK and IKKβ.Results:IKKα,IKKγ,and IκBαincreased upon exposure to IR,thereby affecting nuclear levels of NFκB(phospho-p65).ERK inhibition or si RNA-mediated down-regulation of RAF1 suppressed the post-irradiation survival of the examined lung cancer cell lines.A similar effect was detected on survival upon silencing IKKα/IKKγor inhibiting IKKβ.Conclusions:Exposure of lung cancer cells to IR results in NFκB activation via IKK.The genetic or pharmacological blockage of the RAF1-ERK-IKK-NFκB pathway sensitizes cells to therapeutic doses of radiation.Therefore,the IKK pathway is a promising target for therapeutic intervention in combination with radiotherapy.

Expression of VEGFR2 and NRP-1 in non-small cell lung cancer and their clinical significance

Objective： Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2（VEGFR2） and neuropilin-1（NRP-1） can be biomarkers for clinical treatment. We aimed to investigate the expression levels of VEGFR2 and NRP-1 in human non-small cell lung cancer（NSCLC） and their clinical significance by observing patient prognosis. Methods： VEGFR2 and NRP-1 were assessed by immunohistochemistry（IHC） in 40 patients with NSCLC and in 10 patients with benign lesions of lung; kinase insert domain receptor（KDR） and NRP-1 copy number gain（CNG） was assessed by fluorescence in situ hybridization（FISH）. The distributions of overall survival（OS） and progression-free survival（PFS） were estimated using the Kaplan-Meier method and compared between groups by log-rank test.Results： Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and 55%, respectively. KDR and NRP-1 CNG（＋） were detected in 32.5% and 30% of tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were significantly different than in the control tissue（χ2=11.22, P=0.001; χ2=9.82, P=0.001, respectively）; similar results were obtained using CNGs（χ2=4.39, P=0.036; χ2=3.95, P=0.046, respectively）. Statistically significant correlations were observed with histological grade, clinical TNM stage and the lymph node status（P〈0.05）, but not age, gender or pathology type（P〉0.05）. VEGFR2 showed a strong correlation with NRP-1（Rs=0.68, P=0.00）; similar results were observed with KDR and NRP-1 CNG（Rs=0.32, P=0.04）. Significant differences in OS and PFS were observed between the groups with higher VEGFR2 and NRP-1 and those with lower expression（P〈0.05）. Conclusions： According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can conclude that they play a key role in NSCLC occurrence, development and metastasis and are associated with patient prognosis（P〈0.05 for OS and PFS）. This information will be beneficial for clinical antiangiogenic treatment in NSCLC.

Association between Overexpression of Her-2 and Other Clinicopathologic Prognostic Factors in Breast Cancer in Morocco

Background: Breast cancer is the leading cancer among women. The management depends largely on the knowledge of prognostic factors. The aim of our study is to evaluate the overexpression of Her-2/neu in patients with invasive breast carcinoma in Morocco, and to study the association between this overexpression and otherprognostic factors of breast cancer, such as age, tumor size, tumor grade, hormone receptors, vascular space invasion and lymph node status. Methods: This is a transversal study in which we included patients with invasive breast carcinomas treated at University Hospital Ibn Rochd of Casablanca in radiotherapy-oncology departement between January 2008 and December 2010, having had surgery first. Univariate analysis (Chi 2 test and Student’s test) and multivariate (logistic regression) were performed to study this association. Results: The overexpression of Her-2/neu was found in 29.2% of cases. In univariate analysis, Her-2 positive status was significantly correlated with high-grade tumors and large, to a lymph node, vascular space invasion and negative ER/PR. Age alone does not appear as a factor associated with positive Her-2/neu status. In multivariate analysis, the overexpression of Her 2 was significantly associated only with vascular space invasion, high tumor grade and the negativity of estrogen receptors. Conclusion: In our series, only the high grade, the vascular space invasion and the negative hormone receptors are independent factors associated with overexpression of Her 2/neu. Age does not appear as a factor associated with positive Her-2/neu status.

Müllerian duct anomalies and their effect on the radiotherapeutic management of cervical cancer

Radiotherapy plays a major role in the treatment of cervical cancer. A successful radiotherapy program integrates both external beam and brachytherapy components. The principles of radiotherapy are strongly based on the anatomy of the organ and patterns of local and nodal spread. However, in patients with distorted anatomy, several practical issues arise in the delivery of optimal radiotherapy, especially with brachytherapy. Müllerian duct anomalies result in congenital malformations of the female genital tract. Though being very commonly studied for their deleterious effects on fertility and pregnancy, they have not been recognized for their potential to interfere with the delivery of radiotherapy among patients with cervical cancer. Here, we discuss the management of cervical cancer among patients with Müllerian duct anomalies and review the very sparse amount of published literature on this topic.

The Role of NM23 in Patients with Colorectal Cancer:A Systematic Review and Meta-Analysis

This meta-analysis was carried out to evaluate the relationship between NM23 expression and the prognosis of patients with colorectal cancer. We searched Pub Med, EMBASE and Web of Science for relevant articles. The pooled odd ratios（ORs） and corresponding 95%CI were calculated to evaluate the prognostic value of NM23 expression in patients with colorectal cancer, and the association between NM23 expression and clinicopathological factors. In total, 2289 patients were pooled from 24 available studies. The incorporative OR combined by 16 studies with overall survival showed that high NM23 expression was associated with better overall survival（OR=0.67, 95%CI： 0.49–0.93, P=0.02, I2=56%, Ph=0.004）. And a new estimate without heterogeneity was produced when only combining high-quality studies（OR=0.70, 95%CI： 0.56–0.86, P=0.0007, I2=46%）. In disease free survival（DFS）, we also obtained a good prognosis（OR=0.30, 95%CI： 0.14–0.68, P=0.004）. Although we failed to find any significance in N status（P=0.10）, elevated NM23 expression was related to well tumor differentiation（OR=0.60, 95%CI： 0.44–0.820, P=0.001） and Dukes＇ A＆B（OR=0.55, 95%CI： 0.32–0.95, P=0.03）. These results indicated that over-expressed NM23 might be an indicator of good prognosis, well tumor differentiation and Dukes＇ A＆B of patients with colorectal cancer, but no significance was found in N status.

RAMAN SPECTROSCOPIC STUDY ON PREDICTION OF TREATMENT RESPONSE IN CERVICAL CANCERS

Concurrent chemoradiotherapy(CCRT)is the choice of treatment for locally adv anced cervical cancers;however,tumors exhibit diverse response to treatment.Early prediction of tumor response leads to individualizing treatment regimen.Response evaluation criteria in solid tumors(RECIST),the current modality of tumor response assessment,is often subject ive and carried out at the first visit after treatment,which is about four months.Hence,there is a need for better predictive tool for radioresponse.Optical spectroscopic techniques,sensitive to molecular alteration,are being pursued as potential diagnostic tools.Present pilot study ains to explore the fiber-optic-based Raman spectroscopy approach in prediction of tumor response to CCRT,before taking up extensive in vivo studies.Ex vivo Raman spectra were acquired from biopsies collected from 11 normal(148 spectra),16 tumor(201 spectra)and 13 complete response(151 CR spectra),one partial response(8 PR spectra)and one nonresponder(8 NR spectra)subjects.Data was analyzed using principal component linear discriminant analysis(PC-LDA)followed by leave-one-out cross-validation(LOO-CV).Findings suggest that normal tissues can be efficiently classified from both pre-and post-treated tumor biopsies,while there is an overlap between pre-and post-CCRT tumor tissues.Spectra of CR,PR and NR tissues were subjected to principal component analysis(PCA)and a tendency of classification was observed,corroborating previous studies.Thus,this study further supports the feasibility of Raman spectroscopy in prediction of tumor radioresponse and prospective noninvasive in vivo applications.

Assessment of breast cancer immunohistochemistry and tumor characteristics in Nigeria

BACKGROUND Female breast cancer is the leading type of cancer worldwide with an incidence of approximately 2.1 million in 2018.Hormone receptor status plays a vital role in its management.AIM To determine the molecular expression pattern of biomarkers in breast cancer and their correlation with tumor variables.METHODS This prospective study was designed to analyze expression patterns of estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor(HER2/neu)in breast cancer patients.The dataset has been taken from the Department of Radiotherapy and Oncology of Usmanu Danfodiyo University Teaching Hospital Sokoto,Nigeria from 1 January 2015 to 2 December 2019.The dataset had 259 records and 7 attributes.SPSS version 23.0 for statistical analysis was used.The data analyzed demographic and other clinicopathological characteristics as categorical variables.The mean and standard deviation were determined for the quantitative variable.RESULTS A total of 259 breast cancer cases were included in the study.The mean age was 48.3±11.0,with an age range of 26-80 years and a median age of 46 years.The morphological categories were invasive ductal carcinoma 258(99.6%)and invasive lobular carcinoma 1(0.4%).ER,positivity increased in 73 patients(50%)under the age of 50 years,as well as PR positivity increased in 34 patients(23.6%)under the age of 50 years.HER/2neupositivity decreased in 8 patients(5.6%)under the age of 50 years.Hormonal receptors were statistically significant with clinicopathological characteristics(P<0.05).CONCLUSION Our study showed that ER,PR and HER2/neuexpression had a strong correlation with age,tumor grade,tumor size and lymph node status.Hence,hormone receptor assessment is highly recommended because of its significance in clinical management and prognostication.

Pediatric Nasopharyngeal Rhabdomyosarcoma: About a Case and Review of Literature

Introduction: Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in children, with the head and neck location accounting for up to 40% of cases. The embryonal and alveolar histologic variants are more commonly seen in pediatric patients. The treatment is multimodal and the prognosis of this clinical entity is always gloomy. We report the case of nasopharyngeal rhabdomyosarcoma in a 7-year-old boy child with a good response to early post-therapy. Case Presentation: The patient was diagnosed with nasopharyngeal RMS revealed by a congested nose, ptosis and bilateral blindness, and who received induction chemotherapy followed by concurrent radiotherapy followed by adjuvant chemotherapy. The evolution is marked by a good clinical course but persistence of bilateral blindness. Conclusion: The RMS nasopharyngeal often presents with nonspecific symptoms. Multimodal therapy should be performed including surgery, chemotherapy and radiotherapy.

Role of intraluminal brachytherapy in palliation of biliary obstruction in cholangiocarcinoma:A brief review

Surgery is the only curative treatment for cholangiocarcinoma. However, mostpatients present with advanced disease, and hence are unresectable. Thus, theintent of treatment shifts from curative to palliative in the majority of cases.Biliary drainage with intraluminal brachytherapy is an effective means ofrelieving the malignant biliary obstruction. In this review, we discuss the role ofbrachytherapy in the palliation of obstructive symptoms in extrahepatic cholangiocarcinoma.

BAX G(-248)A Gene Polymorphism and Its Association with Risk of Non-Small Cell Lung Cancer—A Case Control Study

Pro-apoptotic Bcl-2 protein BAX is an important member of mitochondrial dependent apoptosis regulation and ultimately plays a pivotal role in malignancies. A promoter G(-248)A polymorphism in the TP53 binding region of BAX results in differential binding capacity of TP53 protein there by regulating its expression, which has been found to be associated with different clinical outcomes in various malignancies. Presently we aimed to analyze the possible impact of the BAX G(-248)A polymorphism on the risk and other clinical features of non-small cell lung cancer in Indian population. The BAX promoter polymorphism was analyzed in blood samples of 320 subjects with 1:1 case/control ratio by primer-introduced restriction analysis PCR and survival curves were plotted using Kaplan-Meier analysis. It was observed that more than 3-fold increased risk of developing non-small cell lung cancer was associated with homozygous AA genotype of BAX G(-248)A promoter polymorphism in Indian population, with more predominant in smokers with pack-year > 45 (heavy) and using cigarette or huka as their smoking source than homozygous GG genotype. Significant associations was observed between TNM stage (p = 0.037) and histological type (0.02), of non-small cell lung cancer patients with the polymorphism. Patients homozygous for A allele exhibited a significant poor overall survival compared with patients displaying GA + AA or GA or GG genotype [median survival 6.0 vs 9.0, 11.0, and 30.0 months, respectively (p < 0.0001)]. Adenocarcinoma and advanced stage patients with AA genotype showed lower median survival time than squamous cell carcinoma and early stage non-small cell lung cancer patients (median 3.0 and 5.0 vs 8.0 and 9.0 months, respectively). We conclude that the genetic polymorphism G(-248)A in the TP53 binding promoter region of pro-apoptotic genes BAX may contribute to the risk of developing non-small cell lung cancer in Indian population and also may be an important factor for adverse clinical outcome for patients with non-small cell lung cancer.

The Effect of Fullerenol Combined with Cisplatin on the Proliferation of Cervical Cancer HeLa Cells

This study aimed to investigate the effect of fullerenol combined with cisplatin on the proliferation of cervical cancer HeLa cells in order to provide new ideas and laboratory theoretical basis for the clinical treatment of cervical cancer. Cervical cancer cell line HeLa cells in vitro were treated with different concentrations of fullerenol, different concentrations of cisplatin, and different concentrations of fullerenol combined with cisplatin, after 24 h, 48 h, 72 h, microscope changes in cell morphology;MTT assay was used to determine the effect of drugs on the proliferation of HeLa cells. Fullerenol and cisplatin alone can inhibit the proliferation of HeLa cells in a dose-dependent and time-dependent manner;compared with cisplatin alone, different concentrations of fullerenol combined with cisplatin significantly increased the apoptosis rate of HeLa cells (P < 0.05). The inhibition of fullerenol combined with cisplatin on HeLa cells in vitro is more significant, resulting in a stronger anti-cancer effect.

Hypertensive Profile of Metastatic Colorectal Carcinoma Patients Treated with Bevacizumab—A Prospective Study

Background: Bevacizumab is a recombinant humanized monoclonal antibody which targets Vasculoendothelial growth factor (VEGF)-A and prevents its binding to VEGF receptor 2 (VEGFR 2). It is approved in the first and second line treatment of metastatic colorectal cancer along with combination chemotherapy. Hypertension is an on-target and a common side effect of the treatment with bevacizumab. The true incidence of bevacizumab induced hypertension and its grading remains unclear due to paucity of prospective studies in this regard. In our institution, majority of metastatic colorectal cancer patients receive bevacizumab along with cytotoxic chemotherapy. In Indian, a context prospective study on this topic is negligible;so we find it to be of high importance. Objectives: We have conducted a prospective observational study of all metastatic colorectal patients receiving bevacizumab with chemotherapy and satisfying the eligibility criteria. The objective of the study was to assess the incidence and the pattern of hypertension. Materials & Methods: Patients receiving bevacizumab with FOLFOX (5 Fluorouracil, Calcium Leucovorin & Oxaliplatin) or CapeOX (Capecitabine & Oxaliplatin) chemotherapy for metastatic colorectal cancer were enrolled in the study;blood pressure was monitored before bevacizumab administration and also for the next seven days. This was done for all the chemotherapy cycles. Results: 100% of patients developed hypertension of any grade and 20% received treatment as a part of newly detected hypertension. Majority of the patients had grade 1 hypertension. Other grade of hypertension was grade 2. The blood pressure peaked on 6th day of bevacizumab administration. Conclusions: Hypertension of any grade may develop in bevacizumab treated patients. The incidence is very high and it may reach even up to 100% if prospectively and meticulously evaluated for longer period of time.