Journal of Cancer Science and Clinical Therapeutics

Journal Information
EISSN : 2637-5079
Current Publisher: Fortune Journals (10.26502)
Total articles ≅ 93
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Journal of Cancer Science and Clinical Therapeutics; doi:10.26502/jcsct

Natalia Garcia, Mara Ulin, Ayman Al-Hendy, Qiwei Yang
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 487-498; doi:10.26502/jcsct.5079089

Abstract:
Background: The hedgehog pathway (HH) is one of the key regulators involved in many biological events. Malfunction of this pathway is associated with a variety of diseases including several types of cancers. Methods: We collected data from public databases and conducted a comprehensive search linking the HH pathway with female cancers. In addition, we overviewed clinical trials of targeting HH pathway in female cancers. Results: The activation of HH pathway and its role in female cancers, including breast cancer, ovarian cancer, cervical cancer, endometrial cancer, and uterine leiomyosarcoma were summarized. Treatment options targeting SMO and GLI in HH pathway were reviewed and discussed. Conclusions: The hedgehog pathway was shown to be activated in several types of female cancers. Therefore, targeting HH pathway may be considered as a therapeutic option to be acknowledged in the treatment of female cancers.
Ivana Puliafito, Caterina Puglisi, Stefania Marchisotta, Pasquale Malandrino, Paolo Giuffrida, Francesca Esposito, Angela Prestifilippo, Dario Giuffrida
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 229-236; doi:10.26502/jcsct.5079067

Abstract:
Background: Differentiated thyroid carcinoma (DTC) is the most common malignant tumor of the thyroid gland and causes local and/or distant metastases. Differentiated thyroid carcinoma (DTC) is the most common form, representing more than 90% of all thyroid cancers and derives from the follicular cells of the thyroid. Choroidal metastasis from DTC is extremely rare. Only a few cases have been reported in literature. Case Summary: We report the case of a 43-year-old man with differentiated thyroid cancer. He underwent a total thyroidectomy plus a right latero-cervical lymphoadenectomy. Histological examination revealed a 7 mm papillary thyroid cancer, pT3N1b. Firstly treated with locoregional treatment. In February 2012 computer tomography (CT) scan and WBS showed a progression of disease with bilateral lung lesions, bilateral multiple jugular carotid lymphnodes and bone metastases localized in the IV thoracic rib. After progression disease he was treated with Lenvatinib 24 mg daily. Symptomatic choroid metastases were diagnosed 4 years after initial diagnosis, and were treated with external-beam radiation. Although treatment reduced local masses, a rapid progression of multiple metastatic lesions was observed. Conclusion: In our case, progression free survival with lenvatinib was in agreement with data of SELECT trial, this is a rare case of choroidal metastases from DTC.
Phyllis Van Der Ploeg, Meggy P.M. Ottenheijm, Laura A.M. Van Lieshout, Anja Van De Stolpe, Steven L. Bosch, Anna M.J. Thijs, Ruud L.M. Bekkers, Jurgen M.J. Piek
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 283-303; doi:10.26502/jcsct.5079072

Abstract:
Therapy targeting the estrogen receptor (ER) pathway is being explored as a treatment option in ovarian carcinoma. However, studies on the efficacy of anti-estrogen therapy include a broad range of histological subtypes and/or do not select patients based on ER status. This systematic review provides an analysis of literature on the clinical benefit rate (CBR) of anti-estrogen therapy in ER positive high-grade serous carcinomas (HGSC) and on the correlation between ER expression by immunohistochemistry and clinical response. We did not find studies with populations consisting solely of ER positive HGSC. However, we included six studies reporting on 407 evaluable patients of whom 376 were HGSC (92%) and 302 were confirmed ER positive (80%). Anti-estrogen therapy resulted in a CBR of 27-65% and an overall response rate of 0-16%. No correlation was found between ER expression and clinical response. Therefore, ER protein expression alone is not a specific predictor of response. This may result from the incorrect assumption that ER expression equals ER pathway activity, since in the absence of ER activating mutations, ER pathway activity depends on availability of the estradiol ligand. In order to apply effective ER targeted therapy, it is important to develop better predictors to identify (non)-responders.
Beatrix Bicskei, Pia Moltu, Melinda Lillesand, Emma Rewcastle, Irene Kraus Christiansen, Einar G Gudlaugsson, Jannicke M Berland, Emiel Am Janssen, Irene T Ovestad
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 349-364; doi:10.26502/jcsct.5079077

Abstract:
The causative role of HPV infection in a wide range of diseases is well established, highlighting the importance of accurate HPV genotyping techniques applicable to various tissue types and conservation methods. This study compared the performance of the automated INNO-LiPA HPV Genotyping Extra II and the manual Linear Array HPV genotyping assays in diagnostically relevant specimens. Samples with discrepant results were also tested with Anyplex II HPV28 detection assay. DNA from 120 samples, primarily from anogenital and head-neck FFPE tissues and cervical cytology specimens, were analysed. Interclass correlation efficiencies between the assays and percentage and kappa agreements for individual genotypes were calculated. Overall, a high agreement was found between the two genotyping methods (>0.95), however, INNO-LiPA was more likely to identify genotypes in samples indicating low viral load and/or originating from FFPE tissues. Specifically, INNO-LiPA detected more genotypes in FFPE material harbouring multiple HPV infections; in particular HPV51 and 52 were the most affected high-risk genotypes. In contrast, Linear Array identified more low-risk HPV54 infections in both cytology and FFPE specimens. The discrepant genotypes detected by Anyplex resembled more the results of Linear Array than that of INNO-LiPA. We conclude that the assays are highly comparable, but differences may arise in a context dependent manner.
Wei Chen, Xiao-Ping Tan, Jun-Wen Ye, Yan Zhang, Jing-Lin Liang, Mei-Jin Huang
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 325-332; doi:10.26502/jcsct.5079075

Abstract:
Background: To observe the factors related to the survival and prognosis of patients with resectable stage T4 colorectal cancer. Methods: A total of 148 patients with resectable stage T4 colorectal cancer who underwent surgery at the First Affiliated Hospital of Sun Yat-sen University between August, 1994 and December, 2005 were retrospectively analysed. Univariate and multivariate analyses of the associations between clinicopathological variables and survival were analysed using the Cox regression model. Results: The follow-up period ended in December 2010 or at patient death; the 5-year and 10-year overall survival (OS) rates were 49.0% and 32.2%, respectively, and the median OS duration was 25 months. The 5-year and 10-year disease-free survival (DFS) rates were 44.2% and 30. 3%, respectively. In univariate analysis, postoperative pathology indicating lymph node metastasis was associated with patient prognosis in terms of OS (all P< 0.01), and postoperative adjuvant therapy failed to improve OS or DFS (P>0.05). Postoperative pathology indicating lymph node metastasis was also associated with DFS (all P< 0.01). In multivariate analysis, postoperative pathology indicating lymph node metastasis was an independent factor affecting OS and DFS in colorectal cancer patients. Conclusion: The postoperative prognosis of T4 colorectal cancer patients is poor, and postoperative pathology indicating lymph node positivity was an independent factor for OS and DFS.
Muhammad Sohaib Asghar, Sarah Kamran Akbani, Noman Ahmed Khan, Syed Jawad Haider Kazmi, Mohammed Akram, Rumael Jawed, Maira Hassan, Uzma Rasheed
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 382-392; doi:10.26502/jcsct.5079080

Abstract:
Hepatocellular carcinoma is ranked as the sixth most common cancer globally. It also accounts for the second leading determinant of cancer-related mortalities worldwide. In the present day, transarterial chemoembolization (TACE) is the treatment modality of preference for high burden hepatocellular carcinoma. Our study aims to report the efficacy of TACE and alterations in laboratory parameters in patients of hepatocellular carcinoma before and after undergoing TACE in lieu with size >3 cm or 3cm tumor size (p=0.050). After TACE, bilirubin levels were remarkably improved in 3cm tumor size. Serum creatinine worsened in 3 cm tumor size, and SGPT was indifferent in 3cm tumor size. Mean meld score was found improved in both the study groups however, greater improvements were seen in >3cm tumor size group. Downstaging of child-pugh classes was statistically significant in both the study groups (p
Matera Eva-Laure, Fouret Julien, Baulu Estelle, Perrial Emeline, Bousfiha Zineb, Abdelkamel Chettab, Lars Petter Jordheim, Charles Dumontet
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 71-77; doi:10.26502/jcsct.5079052

Abstract:
BCR pathway inhibitors idelalisib and ibrutinib were the first small molecule targeted agents for B-cell malignancies. In spite of encouraging response rates in various forms of B cell diseases, patients will eventually develop relapse due to the emergence of resistant cells. To better identify the possible mechanisms of resistance we developed and characterized idelalisib- and ibrutinib-resistant variants of the human non Hodgkin’s lymphoma cell lines DoHH2 and Daudi. These resistant variants displayed a cross-resistance profile limited to PI3K inhibitors, BTK inhibitors and a SYK inhibitor but not to unrelated agents. A number of alterations were observed in the resistant lines, including a strong reduction of BLINK and the AKT3. A new SNP in PLCgamma2 (Leu848Phe) closely related to a previously reported SNP associated to ibrutinib resistance (Leu845Phe) was observed in both DAUDI-based resistant cell lines but was absent in wild type cells. Resistant lines tended to express larger amounts of CD38 and were found to display enhanced sensitivity to anti-CD38 antibodies. These results identify potential novel mechanisms of resistance to idelalisib and ibrutinib and raise the possibility that cells resistant to BCR pathway inhibitors might possess enhanced sensitivity to anti-CD38 antibodies.
Kumari S
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 91-99; doi:10.26502/jcsct.5079055

Abstract:
Introduction: Patients with Gynaecological malignancies frequently visit the Emergency Department (ED). Knowledge of clinical presentation and their acute management will help in delivering a better care to these patients. Materials and Methods: A Cross sectional study was conducted in the ED of All India Institute of Medical Sciences New Delhi, India from January 1, 2018 to December 31, 2018. The study cohort comprised of fifty patients with gynaecological cancer. Inpatient medical record was evaluated. Results: Median age of fifty patients was 45.5 years (range 18 - 68). Carcinoma cervix was the most common malignancy (28 cases, 56%) followed by carcinoma ovary (14 cases, 28%), carcinoma endometrium (3 cases, 6%), gestational trophoblastic neoplasia (3 cases, 6%), molar pregnancy (1 case, 2%) and leiomyosarcoma (1 case, 2%). Predominant complaints were pain (28%), anuria (22%), bleeding per vaginum (22%) and shortness of breath (14%). Obstructive uropathy was the most common diagnosis (26%) followed by anaemia (18%), electrolyte imbalance (14%) and intestinal obstruction (14%). Bilateral percutaneous nephrostomy and electrolyte correction were the commonest intervention in 12 cases each (24%) followed by antifibrinolytics in 11 cases (22%), pain management in 10 cases (20%) hemodialysis in 9 cases (18%), blood transfusion in 8 cases (16%). Median length of hospital stay was 48 hours (6 – 96 hours). Six patients underwent emergency laparotomy. Of fifty patients two (4%) expired during the stay. Conclusion: Pain was the commonest presentation and appropriately managing pain is a significant contributor to improving quality of life in these patients.
Leona Chang, Krystal Hunter, James Aikins, Spencer Brown, Olga Ostrovsky
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 100-114; doi:10.26502/jcsct.5079056

Abstract:
Objective: (1) Determine if sequential administration of standard chemotherapy (paclitaxel and cisplatin, P/C) with epigenetic drugs effectively targets ovarian cancer and limits toxicity to normal cells. (2) Define whether epigenetic treatment can shorten the exposure to P/C. Methods: Normal cells—adipocyte-derived stem cells (ASC), primary fibroblasts (PF), and human intestinal epithelial cells (HIEC-6)—were treated with 48 h IC50 values of P/C and epigenetic drugs, 5-azacytidine (AZA) and or suberoylanilide hydroxamic acid (SAHA), in combination and sequentially. The least toxic regimens to normal cells were administered to the ovarian cancer cell lines Caov-3, SKOV-3, OVCAR-3. Cell viability after treatments were assessed using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) and cell count assays. Secretome analysis of conditioned medium collected from the treated ovarian cancer cells was performed using ELISA. Results: P/C with AZA and SAHA targeted all ovarian cancer cell lines (82-99% cell death), but also caused significant normal cell death (66-100%). In contrast, P/C followed by AZA or SAHA is less toxic to ASC and PF (25-96% viability) when compared to a four-drug combination therapy (1% viability, p
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