Anti-cancer Immunotherapy Epitope-peptides Vaccination in Patients with Refractory/Persistent Disease of Cervical Cancer and Ovarian Cancer (Phase 1 Studies)

Background: Persistent infection with the high-risk of human papillomavirus (HR-HPVs) is the primary etiological factor of cervical cancer; HR-HPVs express oncoproteins E6 and E7, both of which play key roles in the progression of cervical carcinogenesis. Zinc Finger Nucleases (ZFNs) targeting HPV E7 induce specific shear of the E7 gene, weakening the malignant biological effects, hence showing great potential for clinical transformation. Objective: Our aim was to develop a new comprehensive therapy for better clinical application of ZFNs. We here explored the anti-cancer efficiency of HPV targeted ZFNs combined with a platinum-based antineoplastic drug Cisplatin (DDP) and an HDAC inhibitor Trichostatin A (TSA). Methods: SiHa and HeLa cells were exposed to different concentrations of DDP and TSA; the appropriate concentrations for the following experiments were screened according to cell apoptosis. Then cells were grouped for combined or separate treatments; apoptosis, cell viability and proliferation ability were measured by flow cytometry detection, CCK-8 assays and colony formation assays. The xenograft experiments were also performed to determine the anti-cancer effects of the combined therapy. In addition, the HPV E7 and RB1 expressions were measured by western blot analysis. Results: Results showed that the combined therapy induced about two times more apoptosis than that of ZFNs alone in SiHa and HeLa cells, and much more inhibition of cell viability than either of the separate treatment. The colony formation ability was inhibited more than 80% by the co-treatment, the protein expression of HPV16/18E7 was down regulated and that of RB1 was elevated. In addition, the xenografts experiment showed a synergistic effect between DDP and TSA together with ZFNs. Conclusion: Our results demonstrated that ZFNs combined with DDP or TSA functioned effectively in cervical cancer cells, and it provided novel ideas for the prevention and treatment of HPV-related cervical malignancies.

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Fas gene promoter –670 polymorphism in gynecological cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200602001-00028 ◽

2006 ◽

Vol 16 (Suppl 1) ◽

pp. 179-182 ◽

Cited By ~ 2

Author(s):

M. Ueda ◽

Y. Terai ◽

K. Kanda ◽

M. Kanemura ◽

M. Takehara ◽

...

Keyword(s):

Ovarian Cancer ◽

Cervical Cancer ◽

Cancer Patients ◽

Germ Line ◽

Gynecological Cancer ◽

Gene Promoter ◽

Single Nucleotide ◽

Increased Risk ◽

Significant Difference ◽

Germ Line Polymorphism

Single-nucleotide polymorphism at −670 of Fas gene promoter (A/G) was examined in a total of 354 blood samples from normal healthy women and gynecological cancer patients. They consisted of 95 normal, 83 cervical, 108 endometrial, and 68 ovarian cancer cases. Eighty-three patients with cervical cancer had statistically higher frequency of GG genotype and G allele than 95 controls (P= 0.0353 and 0.0278, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and endometrial or ovarian cancer patients. The Fas −670 GG genotype was associated with an increased risk for the development of cervical cancer (OR = 2.56, 95% CI = 1.08–6.10) compared with the AA genotype. The G allele also increased the risk of cervical cancer (OR = 1.60, 95% CI = 1.05–2.43) compared with the A allele. Germ-line polymorphism of Fas gene promoter −670 may be associated with the risk of cervical cancer in a Japanese population.

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Myometrial Responses to Beta-Adrenoceptor Antagonists in Gynecological Malignancies

Gynecologic and Obstetric Investigation ◽

10.1159/000513718 ◽

2021 ◽

pp. 1-8

Author(s):

Beata Modzelewska ◽

Marcin Jóźwik ◽

Tomasz Kleszczewski ◽

Stanisław Sulkowski ◽

Maciej Jóźwik

Keyword(s):

Ovarian Cancer ◽

Cervical Cancer ◽

Reference Group ◽

Ex Vivo ◽

Contractile Activity ◽

Organ Bath ◽

Human Uterus ◽

Uterine Contractility ◽

Beta Adrenoceptor ◽

Gynecological Malignancies

Objective: The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. Design: This was a controlled and prospective ex vivo study. Setting: The work was conducted as a collaboration between 4 academic departments. Materials and Methods: Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; N = 15), and ovarian (N = 15), endometrial (N = 15), synchronous ovarian-endometrial (N = 3), and cervical cancer (N = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. Results: Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all p < 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both p < 0.001). Limitations: These results require now to be placed into a firm clinical context. Conclusions: Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.

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Evaluation of Dimer of Epicatechin from an Endophytic Fungus Curvularia australiensis FC2AP on Acute Toxicity Levels, Anti-Inflammatory and Anti-Cervical Cancer Activity in Animal Models

Molecules ◽

10.3390/molecules26030654 ◽

2021 ◽

Vol 26 (3) ◽

pp. 654

Author(s):

Vellingiri Manon Mani ◽

Arockiam Jeyasundar Parimala Gnana Soundari ◽

Balamuralikrishnan Balasubramanian ◽

Sungkwon Park ◽

Utthapon Issara ◽

...

Keyword(s):

Cervical Cancer ◽

Acute Toxicity ◽

Endophytic Fungus ◽

Lethal Dose ◽

Chemotherapeutic Agents ◽

Cancer Drug ◽

Dependent Manner ◽

Anti Cancer ◽

Albino Mice ◽

Anti Inflammatory

Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells or altering the properties of the cells. In order to reduce the severity of the side effects caused by the chemically synthesized therapeutic agents, the current research developed an anti-cancer agent dimer of epicatechin (DoE), a natural bioactive secondary metabolite (BSM) mediated from an endophytic fungus Curvularia australiensis FC2AP. The investigation has initiated with the evaluation of inhibiting the angiogenesis which is a main activity in metastasis, and it was assessed through Hen’s Egg Test on Chorio Allantoic Membrane (HET-CAM) test; the BSM inhibited the growth of blood vessels in the developing chick embryo. Further the DoE was evaluated for its acute toxicity levels in albino mice, whereas the survival dose was found to be 1250 mg/kg and the lethal dose was 1500 mg/kg body weight of albino mice; hematological, biochemical, and histopathological analyses were assessed. The anti-inflammatory responses of the DoE were evaluated in carrageenan induced Wistar rats and the reduction of inflammation occurred in a dose-dependent manner. By fixing the effective dose for anti-inflammation analysis, the DoE was taken for the anti-cervical cancer analysis in benzo (a) pyrene induced female Sprague-Dawley rats for 60 days trial. After the stipulated days, the rats were taken for hematological antioxidants, lipid peroxidation (LPO), member bound enzymes, cervical histopathological and carcinogenic markers analyses. The results specified that the DoE has the capability of reducing the tumor in an efficient way. This is the first report of flavonoid-DoE production from an endophytic fungus C. australiensis has the anticancer potentiality and it can be stated as anti-cancer drug.

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Colorectal Cancer Risk in Women with Gynecologic Cancers—A Population Retrospective Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm10143127 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3127

Author(s):

Szu-Chia Liao ◽

Hong-Zen Yeh ◽

Chi-Sen Chang ◽

Wei-Chih Chen ◽

Chih-Hsin Muo ◽

...

Keyword(s):

Colorectal Cancer ◽

Ovarian Cancer ◽

Cervical Cancer ◽

Cohort Study ◽

Cancer Patients ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Gynecologic Cancer ◽

Ovarian Cancers ◽

Increased Risk

We conducted a retrospective cohort study to evaluate the subsequent colorectal cancer (CRC) risk for women with gynecologic malignancy using insurance claims data of Taiwan. We identified patients who survived cervical cancer (N = 25,370), endometrial cancer (N = 8149) and ovarian cancer (N = 7933) newly diagnosed from 1998 to 2010, and randomly selected comparisons (N = 165,808) without cancer, matched by age and diagnosis date. By the end of 2011, the incidence and hazard ratio (HR) of CRC were estimated. We found that CRC incidence rates were 1.26-, 2.20-, and 1.61-fold higher in women with cervical, endometrial and ovarian cancers, respectively, than in comparisons (1.09/1000 person–years). The CRC incidence increased with age. Higher adjusted HRs of CRC appeared within 3 years for women with endometrial and ovarian cancers, but not until the 4th to 7th years of follow up for cervical cancer survivals. Cancer treatments could reduce CRC risks, but not significantly. However, ovarian cancer patients receiving surgery alone had an incidence of 3.33/1000 person–years for CRC with an adjusted HR of 3.79 (95% CI 1.11–12.9) compared to patients without any treatment. In conclusion, gynecologic cancer patients are at an increased risk of developing CRC, sooner for those with endometrial or ovarian cancer than those with cervical cancer.

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P53 as a target for anti-cancer immunotherapy

Molecular Medicine Today ◽

10.1016/s1357-4310(97)01003-4 ◽

1997 ◽

Vol 3 (4) ◽

pp. 160-167 ◽

Cited By ~ 21

Author(s):

Hailei L. Chen ◽

David P. Carbone

Keyword(s):

Cancer Immunotherapy ◽

Anti Cancer

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2105 Phase 1 trial of intraperitoneal radioimmunotherapy for ovarian cancer

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/s0360-3016(97)85681-7 ◽

1996 ◽

Vol 36 (1) ◽

pp. 329

Author(s):

Ruby Meredith ◽

Ronald Alvarez ◽

Edward Partridge ◽

M.B. Khazaeli ◽

Gene Plott ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase 1 ◽

Phase 1 Trial

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Autoimmune Responses in Oncology: Causes and Significance

International Journal of Molecular Sciences ◽

10.3390/ijms22158030 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8030

Author(s):

Halin Bareke ◽

Pablo Juanes-Velasco ◽

Alicia Landeira-Viñuela ◽

Angela-Patricia Hernandez ◽

Juan Jesús Cruz ◽

...

Keyword(s):

Cancer Immunotherapy ◽

Protein Microarrays ◽

Cross Reactivity ◽

Fine Tuning ◽

Cancer Treatments ◽

Aberrant Expression ◽

Specificity And Sensitivity ◽

Anti Cancer ◽

Life Threatening ◽

Considerable Impact

Specific anti-tumor immune responses have proven to be pivotal in shaping tumorigenesis and tumor progression in solid cancers. These responses can also be of an autoimmune nature, and autoantibodies can sometimes be present even before the onset of clinically overt disease. Autoantibodies can be generated due to mutated gene products, aberrant expression and post-transcriptional modification of proteins, a pro-immunogenic milieu, anti-cancer treatments, cross-reactivity of tumor-specific lymphocytes, epitope spreading, and microbiota-related and genetic factors. Understanding these responses has implications for both basic and clinical immunology. Autoantibodies in solid cancers can be used for early detection of cancer as well as for biomarkers of prognosis and treatment response. High-throughput techniques such as protein microarrays make parallel detection of multiple autoantibodies for increased specificity and sensitivity feasible, affordable, and quick. Cancer immunotherapy has revolutionized cancer treatments and has made a considerable impact on reducing cancer-associated morbidity and mortality. However, immunotherapeutic interventions such as immune checkpoint inhibition can induce immune-related toxicities, which can even be life-threatening. Uncovering the reasons for treatment-induced autoimmunity can lead to fine-tuning of cancer immunotherapy approaches to evade toxic events while inducing an effective anti-tumor immune response.

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The risk of breast, cervical, endometrial and ovarian cancer in oral contraceptive users

Medicinski pregled ◽

10.2298/mpns1010657v ◽

2010 ◽

Vol 63 (9-10) ◽

pp. 657-661 ◽

Cited By ~ 5

Author(s):

Milena Veljkovic ◽

Slavimir Veljkovic

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cervical Cancer ◽

Oral Contraceptive ◽

Oral Contraceptives ◽

Young Women ◽

Contraceptive Use ◽

Epidemiologic Studies ◽

Oral Contraceptive Use ◽

Increased Risk

Introduction. Oral contraceptives, mainly combined monophasic pills, are widely used by young women who expect their physicians to prescribe them safe drugs which will not harm their health and which will simplify their life. Numerous epidemiologic studies have been performed to determine the relation between oral contraceptive use and the development of neoplasms. Breast cancer. An increased incidence of breast cancer has occurred simultaneously with the growing use of oral contraceptives. The possibility of a link between the oral contraceptive use and breast cancer has led to intensive research, but studies have provided inconsistent results causing confusion among clinicians. It was noticed that the risk of breast cancer was slightly elevated in current and recent young oral contraceptives users. That finding could be influenced by a detection bias or could be due to the biologic effect of the pills. The absolute number of additional breast cancer cases will be very small because of low baseline incidence of the disease in young women. Oral contraceptives probably promote growth of the already existing cancer, they are probably promoters not initiators of breast cancer. The available data do not provide a conclusive answer that is need. Cervical cancer. Numerous factors may influence the development of cervical cancer. The evidence suggests that current and recent oral contraceptive users have an increased risk of cervical cancer which decline after discontinuation of the application of medication. Oral contraceptives might increase the biological vulnerability of the cervix. Cervical cancer develops slowly over a long time period and can be effectively prevented by periodic cervical screening. Fortunately, oral contraceptives do not mask abnormal cervical citology. Conclusions regarding invasive cervical cancer and oral contraceptive use are not definitive but if there is any increased risk, it is low. Endometrial cancer. In oral contraceptive users the endometrium is almost under the influence of progestin component which suppresses endometrial mitotic activity and its proliferation. Most epidemiologic studies show that oral contraceptives reduce the risk of endometrial cancer and that this protective effect exists many years after the discontinuation of medication. Ovarian cancer. It has been long known that the oral contraceptive use causes protective an ovulation and reduces the risk of ovarian cancer. This powerful reduction is the best demonstrated major benefit of oral contraception. This protection is especially observed in nulliparous and seems to persist for many years after the discontinuation of medication.

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