Discovery of PF-06873600, a CDK2/4/6 Inhibitor for the Treatment of Cancer.

Control of the cell cycle through selective pharmacological inhibition of CDK4/6 has proven beneficial in the treatment of breast cancer. Extending this level of control to additional cell cycle CDK isoforms represents an opportunity to expand to additional tumor types and potentially provide benefits to patients that develop tumors resistant to selective CDK4/6 inhibitors. However, broad-spectrum CDK inhibitors have a long history of failure due to safety concerns. In this approach, we describe the use of structure-based drug design and Free-Wilson analysis to optimize a series of CDK2/4/6 inhibitors. Further, we detail the use of molecular dynamics simulations to provide insights into the basis for selectivity against CDK9. Based on overall potency, selectivity, and ADME profile, PF-06873600 (22) was identified as a candidate for the treatment of cancer and advanced to phase 1 clinical trials.

Ocular Injury in Cosmetic Laser Treatments of the Face.

BACKGROUND: The eye is a vulnerable and commonly injured organ in cosmetic laser procedures of the face. Treatment of the eyelids and periorbital areas increases this risk, especially when ocular protection devices are not used or are removed during the procedure. A study has shown that injury from laser epilation of the periocular areas is one of the most common causes of litigation in cutaneous laser surgery. OBJECTIVE: The goal of this review is to determine the causes of ocular injury in cosmetic laser procedures and derive lessons on critical safety elements to prevent future injury. METHODS: We conducted a review of the current literature through a PubMed search on case reports of ocular injury in cosmetic laser treatments of the face. Twenty-one cases are examined. RESULTS: In more than 62 percent of cases, ocular protection was not used or protection was used but removed during the procedure to treat areas close to the eye. However, despite the proper use of intraocular corneal shields and wavelength-specific goggles, accidents occurred in 33 percent of cases. CONCLUSION: Ocular protection devices are essential to prevent most cases of laser-induced eye injury. Use of high fluence and long wavelength lasers increases the risk of ocular injury due to deeper penetration of the organ by radiation. Inadequate cooling between pulses also predisposes to injury by cosmetic lasers.

Penile squamous cell carcinoma: a review of the literature and case report treated with Mohs micrographic surgery.

The majority of penile carcinoma is squamous cell carcinoma. Although uncommon in the United States, it represents a larger proportion of cancers in the underdeveloped world. Invasive squamous cell carcinoma may arise from precursor lesions or de novo , and has been associated with lack of circumcision and HPV infection. Early diagnosis is imperative as lymphatic spread is associated with a poor prognosis. Radical surgical treatment is no longer the mainstay, and penile sparing treatments now are often used, including Mohs micrographic surgery. Therapeutic decisions should be made with regard to the size and location of the tumor, as well as the functional desires of the patient. It is critical for the dermatologist to be familiar with the evaluation, grading/staging, and treatment advances of penile squamous cell carcinoma. Herein, we present a review of the literature regarding penile squamous cell carcinoma, as well as a case report of invasive squamous cell carcinoma treated with Mohs micrographic surgery.

Penile squamous cell carcinoma: a review of the literature and case report treated with Mohs micrographic surgery

Abstract: The majority of penile carcinoma is squamous cell carcinoma. Although uncommon in the United States, it represents a larger proportion of cancers in the underdeveloped world. Invasive squamous cell carcinoma may arise from precursor lesions or de novo , and has been associated with lack of circumcision and HPV infection. Early diagnosis is imperative as lymphatic spread is associated with a poor prognosis. Radical surgical treatment is no longer the mainstay, and penile sparing treatments now are often used, including Mohs micrographic surgery. Therapeutic decisions should be made with regard to the size and location of the tumor, as well as the functional desires of the patient. It is critical for the dermatologist to be familiar with the evaluation, grading/staging, and treatment advances of penile squamous cell carcinoma. Herein, we present a review of the literature regarding penile squamous cell carcinoma, as well as a case report of invasive squamous cell carcinoma treated with Mohs micrographic surgery.

The basic science of dermal fillers: past and present Part I: background and mechanisms of action.

Dermal fillers have provided a safe and effective means for aesthetic soft tissue augmentation, and have experienced a dramatic increase in popularity during the past 10 years. Much focus has been placed upon filler technique and patient outcomes. However, there is a relative lack of literature reviewing the basic science of dermal fillers, which is vital to a physician's understanding of how each product behaves in vivo. Part I of this article reviews the basic science and evolution of both historical and contemporary dermal fillers; Part II examines their adverse effects. We endeavor to provide the physician with a practical approach to choosing products that maximize both aesthetic outcome and safety.

The basic science of dermal fillers: past and present Part II: adverse effects.

The ideal dermal filler should offer long-lasting aesthetic improvement with a minimal side-effect profile. It should be biocompatible and stable within the injection site, with the risk of only transient undesirable effects from injection alone. However, all dermal fillers can induce serious and potentially long-lasting adverse effects. In Part II of this paper, we review the most common adverse effects related to dermal filler use.

Mohs micrographic surgery for the treatment of melanoma.

For melanoma treatment, the primary goal is complete removal with histologically negative margins. Mohs micrographic surgery (MMS) has been extensively used and studied for the treatment of nonmelanoma skin cancer, particularly at sites where tissue conservation is vital. The use of MMS for melanoma treatment has yet to become widely accepted owing to difficulties in histologic interpretation, among other factors. MMS may offer lower recurrence rates and improved survival when compared with historical controls for standard excision. Continued advances in MMS technique and immunohistochemical staining have allowed the technique to gain further support.