Expression and Clinical Significance of HMGB1 and RAGE in Cervical Carcinoma

OBJECTIVE To study the expression level and clinical significance of HMGB1 and RAGE in cervical squamous epithelial carcinoma. METHODS Real time quantitative polymerase chain reaction （qRT-PCR） was employed to examine the expression of HMGB1 （high mobility group box protein1）, and RAGE （receptor for advanced glycation endproducts） in 60 cervical squamous epithelial carcinomas （CSEC）, their paraneoplastic tissues （PS） and 30 normal cervix tissues （NCS）. RESULTS The expression of HMGB1 in the CSEC samples and PS was similar （P〉0.05）, but higher compared to NCS （P〈0.05）. Overexpression of HMGB1 in the CESC tissues was significantly correlated with the tumor （P〈0.05）, and the presence of metastasis （P〈0.01）, but not correlated with the tumor diameter or tumor grade.RAGE expression was not significantly different among these tissue types, and showed no significant correlation with the the tumor stage, diameter or grade. But there was a significant positive correlation between RAGE expression and CSEC metastasis. CONCLUSION The results suggest that HMGB1 may be related to the proliferation, progression and metastasis of CSEC. The relationship of HMGBI/RAGE may be of importance for CSEC metastasis. HMGB1 presents a new potential gene target for prevention and treatment of CSEC. Study of HMGBI/RAGE expression will offer an experimental foundation for understanding the pathogenesis of CSES.

Pembrolizumab as a novel therapeutic option for patients with refractory thymic epithelial tumor:A case report

BACKGROUND Thymic epithelial carcinomas are rare and have a poor prognosis.Treatment of thymic epithelial carcinoma is multimodal and includes surgery,post-operative radiation therapy,adjuvant and neoadjuvant chemotherapy,or exclusive chemotherapy based on disease resectability.However,there is currently no standard treatment regimen for metastatic and recurrent thymic carcinoma.CASE SUMMARY A 45-year-old Caucasian male,with no past medical history,presented with hepatalgia and a cervical mass.A computed tomography(CT)scan showed multiple suspect lesions in the lungs,liver,and anterior mediastinum associated with mediastinal and cervical adenopathy.CT-guided percutaneous biopsies of the liver lesions and anterior mediastinal mass were performed,confirming the histopathology of thymic epithelial carcinoma.Management consisted of several chemotherapy regimens and radiation therapy,administered between April 2016 and December 2018.The patient achieved complete metabolic response.Fluorodeoxyglucose positron emission tomography/CT performed in June 2019 showed disease relapse,with reappearance of a large hypermetabolic hepatic mass and involvement of mediastinal and axillary lymph nodes.Intravenous pembrolizumab(200 mg,every 3 wk)was administered after two prior systemic therapies.The patient’s response to treatment was last documented on March 5,2020.CONCLUSION Pembrolizumab was successful in treatment of a patient with programmed deathligand 1-negative metastatic thymic carcinoma,pretreated with chemotherapy.

Clinical characteristics and survival of patients with normal-sized ovarian carcinoma syndrome: Retrospective analysis of a single institution 10-year experiment

BACKGROUND Normal size ovarian cancer syndrome(NOCS)is a challenge for clinicians regarding timely diagnosis and management due to atypical clinical and imaging features.It is extremely rare with only a few cases reported in the literature.More data are needed to clarify its biological behavior and compare the differences with abnormal size ovarian cancer.AIM To assess the clinical and pathological features of NOCS patients treated in our institution in the last 10 years and to explore risk factors for relapse and survival.METHODS Patients who were pathologically diagnosed with NOCS between 2008 and 2018 were included.Papillary serous ovarian carcinoma(PSOC)patients were initially randomly recruited as the control group.Demographics,tumor characteristics,treatment procedures,and clinical follow-up were retrospectively collected.Risk factors for progression-free survival and overall survival were assessed.RESULTS A total of 110 NOCS patients were included;80(72.7%)had primary adnexal carcinoma,two(1.8%)had mesotheliomas,18(16.4%)had extraovarian peritoneal serous papillary carcinoma,and eight(7.3%)had metastatic tumors.Carbohydrate antigen(CA)125 and ascites quantity were lower in the NOCS cohort than in the PSOC group.The only statistically significant risk factors for worse overall survival(P<0.05)were the levels of CA199 and having fewer than six chemotherapy cycles.The 1-year,3-year,and 5-year survival rates were 75.5%,27.7%,and 13.8%,respectively.CONCLUSION The clinical symptoms of the NOCS group are atypical,and the misdiagnosis rate is high.Ascites cytology and laparoscopic exploration are valuable in the early diagnosis to avoid a misdiagnosis.The level of CA199 is the most important predictor of overall survival,and more than six cycles of chemotherapy contributes to the increased survival rates of NOCS patients.

Three Weeks Carboplatin/Paclitaxel versus Weekly Regimen in Egyptian Women Cohort Treated for Ovarian Carcinoma

Introduction: Epithelial Ovarian Carcinoma (EOC) comprises the vast majority (almost 90%) of ovarian carcinomas. Chemotherapy is the main treatment in ovarian cancers. The standard of care in the chemotherapeutic is the combination of a platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel). Studies were done to determine whether this combination to be given weekly or every 3 weeks. Patient and Method: Inclusion criteria: 1) Female patients between the ages of 17 - 78 years. 2) Baseline hematological, renal and liver laboratory profiles were within accepted ranges. 3) Performance status of the patients was 0-II. 4) Patients were pathologically proven ovarian cancer. 5) A follow-up period for at least 6 months was required. Exclusion criteria: 1) Patients who had double malignancy were excluded. 2) Performance status more than II. 3) Other comorbidity. Results: We reviewed 69 female patients with EOC, with 60% received every three weeks regimen. Mean age was 53.22 years. At a median follow up of 45.9 months, there was no significant different between the two protocols in terms of mean PFS, 62.35 months (95% CI: 50.08 - 74.63 months) for the three-weekly cohort, and 69.25 months (95% CI: 55.24 - 83.26 months) for weekly protocol (p = 0.613). The three weekly regimen patients had a higher incidence of hospital admission (40% vs 18.5% for the weekly protocol patients), but it didn’t reach a statistical significance (p = 0.063). The three weekly protocol had a significantly higher incidence of causing a neutropenic fever (p = 0.003). Conclusion: In our cohort of Egyptian women with EOC, no significant difference in PFS was found when compared the weekly Carboplatin/paclitaxel when compared to the classic three weeks, although the weekly protocol may be causing less febrile neutropenia and fewer hospital admissions.

Clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma

Objective:To assess the clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma (EOC).Methods:A retrospective study of young EOC inpatients (≤40 years old) was performed during January 1994 and December 2010 in eight institutions.Results:Data were analyzed from 94 patients treated with fertility-sparing surgery with a median follow-up time of 58.7 months.As histologic grade increased,overall survival (OS) and disease-free survival (DFS) of patients receiving fertility-sparing surgery declined.Neither staging surgery nor laparoscopy of early stage EOC with conservative surgery had a significant effect on OS or DFS.Normal menstruation recommenced after chemotherapy in 89% of the fertility-sparing group.Seventeen pregnancies among twelve patients were achieved by the end of the follow-ups.Conclusions:Fertility-sparing treatment for patients with EOC Stage I Grade 1 could be cautiously considered for young patients.The surgical procedure and surgical route might not significantly influence the prognosis.Standard chemotherapy is not likely to have an evident impact on ovarian function or fertility in young patients.

Evaluation of whether serum tumor markers in patients with epithelial ovarian carcinoma change following chemotherapy

Background Phenotypic and genotypic heterogeneity is a known feature of many cancers.Whether serum tumor marker kinds vary and change following chemotherapy is still unclear.The aim of this study was to investigate whether there is a change in the expression of serum tumor markers following chemotherapy,and the potential clinical significance in patients with epithelial ovarian carcinoma （EOC） or primary serous peritoneal carcinoma （PSPC）.Methods Samples were collected before surgery,during chemotherapy and during follow-up for enzyme-linked immunosorbent assay （ELISA）-based evaluation of serum CA-125,CA19-9 and CP2 levels in patients with EOC or PSPC who had received primary debulking surgery followed by adjuvant chemotherapy.In total,72 patients were examined,including 37 patients with recurrent lesions and 35 patients receiving first-line chemotherapy.Results In 35 de novo patients,20% （7/35） demonstrated a significant changed serum tumor marker kinds among whom the patients with mucinous carcinoma （57.1%,4/7） showed resistance to chemotherapy.In the 37 recurrent patients,51.4% （19/37） had changed serum tumor markers,of whom 57.9% （11/19） presented with serous carcinoma.There was no significant difference in median progression-free survival or overall survival in patients with drug-sensitive or drug-resistant recurrence in patients with changed tumor marker kinds relative to those with unchanged markers.However,for patients with changed serum tumor markers there was a trend towards prolonged survival compared with the unchanged serum tumor marker group.In the 17 patients with secondary recurrence,37.5% （6/17） had changed tumor marker levels.The ratios of CA-125/CP2 and CA-125/CA19-9 were significantly different after either chemotherapy or recurrence.Conclusions Serum tumor marker expression in patients with EOC or PSPC may change after chemotherapy or recurrence,indicating that in addition to the markers that are abnormal before surgery,those markers that are normalshould also be monitored during chemotherapy and follow-up.

Therapeutic strategy in the management of stage Ⅱ -Ⅳ epithelial ovarian carcinoma

To investigate the optimal time of debulkingin Stage Ⅱto stage Ⅳ epithelial ovarian carcinoma,considering corresponding advantages of both surgeryand chemotherapy. Methods From January 1989 to December 1996,ninety-five stage Ⅱ to stage Ⅳ ovarian cancer patientswere treated under two different regimens. Group A-76 cases (2 cases in Ⅱ a stage, 4 cases in Ⅱ b stage,6 cases in Ⅱ c stage, 58 cases in Ⅲ c Stage and 7cases in Ⅳ stage) was managed according to atraditional surgery-chemotherapy regimen; and groupB-19 cases (17 cases in Ⅲ c stage and 2 cases in Ⅳstage) was managed with a chemotherapy-surgery-chemotherapy regimen. Results The optimal debulking rate (no macroscopicresidual or residual < 2 cm) in group A was significantlylower than in group B, being 32.9% (25/76) and68.4% (13/19), respectively (P < 0.001 ). Theavenge survival time of those with a residual focus>2 cm was shorter than those with a residual focus< 2 cm, in both groups. Sixteen out of the 51 patientswith a residual focus > 2 cm had a second debulkingoperation, among whom 7 had preoperativechemotherapy. All of these 7 patients had either noresiduals or residual < 2 cm. In 9 cases withoutpreoperative chemotherapy, the residuals were all> 2 cm. The average survival time among these twogroups were significantly different (P < 0. 01 ). Conclusion (1 ) For those patients in whom optimaldebulking was clinically assessed to be possible, timelyoperation is mandatory. (2) For those inoperableadvanced cases, chemotherapy- surgery- chemotherapyregimen is recommended. (3) For those with residuals>2 cm and were assessed to be difficult to eradicateduring second-look operation, multi-routechemotherapy (intro-arterial, intraperitoneal, andsystematic) should be given before going on thesecond debulking operation. Positive attitude andproper regimen would offer better results. (4) Amulticenter prospective study would give more decisiveconclusion.

History of intraperitoneal platinum drug delivery for ovarian cancer and its future applications

Intraperitoneal(IP)delivery of cisplatin was developed in the 1970s based on a strong pharmacologic rationale and rodent models.Its advantage over intravenous(IV)administration was supported initially by observational studies in treating recurrent ovarian cancer and eventually by better outcomes from IP vs.IV cisplatin in randomized studies in patients undergoing optimal surgical debulking at diagnosis.In the past two decades,with the introduction of novel anticancer interventions(such as taxanes,bevacizumab,inhibitors of DNA repair,and immune check point inhibitors),advantages of IP drug delivery are less clear and concerns are raised on cisplatin's therapeutic index.The discovery of BRCA genes and their key role in DNA repair,on the other hand,have strengthened the rationale for IP drug delivery:high grade serous cancers arising in the Mullerian epithelium in association with hereditary or somatic BRCA function inactivation are linked to peritoneal spread of cells that-while initially sensitive-are prone to emergence of platinum resistance.Therefore,selection of patients based on genomic features and focusing on the better tolerated IP carboplatin are ongoing.Recent examples of leveraging the peritoneal route include(1)targeting the cell membrane copper transport receptor-that is shared by platinums-by the combination of the proteasome inhibitor bortezomib and IP carboplatin;and(2)enhancing IP 5-fluoro-2-deoxyuridine cytotoxicity when coupled with PARP inhibition.